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ObjectiveTo investigate the mechanism of ethyl acetate extract of Tibetan medicine dampness bud Gentianopsis paludosa in the prevention and treatment of recurrent ulcerative colitis （UC） in rats with dampness-heat in large intestine syndrome based on the apoptotic pathway mediated by the B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax）. MethodUsing the disease-syndrome combination method， a recurrent UC model of dampness-heat in large intestine syndrome was constructed in rats. Seventy SPF-grade male SD rats were randomly divided into control group， model group， high-， medium-， and low-dose ethyl acetate of G.paludosa groups （150， 75， 37.5 mg·kg-1）， and mesalazine group （135 mg·kg-1）. The rats were orally administered with respective drugs for 14 days. The general conditions of the rats were recorded， and colon length and mucosal damage were observed. The colon wet weight index and organ coefficients of the liver， spleen， and thymus were calculated. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-6 （IL-6） and interleukin-1β （IL-1β） in the serum of each group. Hematoxylin-eosin （HE） staining was performed to observe pathological changes in the colon. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） was used to detect apoptosis in colonic epithelial cells. Western blot was used to measure the expression levels of Bcl-2， Bax， Caspase-3， Caspase-9， Zona Occludens-1 （ZO-1）， Claudin3， and Occludin in colonic tissue. Immunohistochemistry （IHC） was used to observe the expression of Bax and Caspase-3 in colonic epithelial cells. ResultCompared with the control group， the model group showed significant increases in the disease activity index （DAI） score， colonic mucosal damage index （CMDI）， intestinal epithelial apoptosis， liver and spleen indexes， and levels of inflammatory factors IL-1β and IL-6 in the serum （P<0.01）， decreased expression of intestinal mucosal protective proteins ZO-1， Claudin3， and Occluding （P<0.01）， increased expression of pro-apoptotic proteins Bax， Caspase-3， and Caspase-9 （P<0.01）， and decreased expression of anti-apoptotic protein Bcl-2 （P<0.01）. Compared with the model group， the high-， medium-， and low-dose ethyl acetate of G.paludosa groups all significantly improved the general condition of the rats， reduced colonic lesions， decreased intestinal epithelial cell apoptosis， reduced liver and spleen indexes， upregulated the expression of ZO-1， Claudin3， Occludin， and Bcl-2 proteins， and downregulated the expression of Bax， Caspase-3， and Caspase-9 proteins， with the high- and medium-dose ethyl acetate of G.paludosa groups showing the superior effects （P<0.05， P<0.01）. ConclusionEthyl acetate of G.paludosa can alleviate colonic mucosal damage and exert a therapeutic effect on UC by regulating the Bcl-2/Bax signaling pathway.
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Via an insufficient coat protein complex I (COPI) retrieval signal, the majority of SARS-CoV-2 spike (S) is resident in host early secretory organelles and a tiny amount is leaked out in cell surface. Only surface-exposed S can be recognized by B cell receptor (BCR) or anti-S therapeutic monoclonal antibodies (mAbs) that is the trigger step for B cell activation after S mRNA vaccination or infected cell clearance by S mAbs. Now, a drug strategy to promote S host surface exposure is absent. Here, we first combined structural and biochemical analysis to characterize S COPI sorting signals. A potent S COPI sorting inhibitor was then invented, evidently capable of promoting S surface exposure and facilitating infected cell clearance by S antibody-dependent cellular cytotoxicity (ADCC). Importantly, with the inhibitor as a probe, we revealed Omicron BA.1 S is less cell surface exposed than prototypes because of a constellation of S folding mutations, possibly corresponding to its ER chaperone association. Our findings not only suggest COPI is a druggable target against COVID-19, but also highlight SARS-CoV-2 evolution mechanism driven by S folding and trafficking mutations.
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BACKGROUND:Surface modification of orthopedic implants can reduce or prevent bacterial adhersion. Bacteriostatic and bactericidal ingredients released from special coating of metal surfaces prevent orthopedic surgery infection. OBJECTIVE:To prepare hydroxyapatite/nano-silver composite coating on the surface of medical titanium based on different preparation parameters and to observe the release properties of silver ions on the composite material surface in the simulated body fluid. METHODS:Using pulse electrochemical methods, hydroxyapatite and nano-silver were deposited in the solution containing silver, calcium and phosphate ions. Scanning electron microscopy, X-ray diffraction and energy dispersive spectroscopy were used to characterize its morphology and composition. The composite titanium materials containing 0.5, 1 mmol/L silver were immersed in the simulated body fluid, and Ag+concentration was detected by atomic absorption spectrometry at the different time points. RESULTS AND CONCLUSION:Nanoparticles were uniformly distributed in the coating which was interwoven with the nano needle-like hydroxypatite and dot-like silver particles. After high temperature processing, the coating became denser, and hydroxypatite became more crystal and silver particles exhibited no agglomeration. In the simulated body fluid, Ag+release was maximal at 1-7 days and became stable at 7-30 days which maintained an effective antimicrobial concentration. The material containing 0.5 mmol/L Ag+showed a lower amount of Ag+released than cytotoxic concentration at 30 days, but the material containing 1 mmol/L Ag+could release the total of Ag+close to the critical value of celltoxicity at 30 days. Above al , the material containing 0.5 mmol/L Ag+is more secure in the clinical application.
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In order to investigate the feasibility of the modified chitosan-gelatin crosslinked membrane (MC-Gel) and chitosan-gelatin crosslinked membrane (CS-Gel) to be a potential biomaterial for corneal regeneration, we evaluated their physicochemical properties and intraocular biocompatibility in this study. White light transmission and permeability of these membranes were detected. Results showed that white light transmission of both membranes was above 90% at 500 nm, which was similar to that of human cornea. The glucose, tryptophan and NaCl permeability of MC-Gel membrane and CS-Gel membrane was better than or similar to those of human cornea. The methylthiazol tetrazolium (MTT) assay was used to assess cell viability and proliferation. Also, interlamellar corneal transplantation was carried out to evaluate ophthalmic biocompatibility of MC-Gel membrane and CS-Gel membrane. Results indicated that MC-Gel membranes could support the proliferation of HCEC and displayed good intraocular biocompatibility when implanted into rabbits. No severe inflammatory reaction occurred after transplantation and the implanted MC-Gel membrane degraded completely 16 weeks post-operation. Due to its good physicochemical properties and biocompatibility, MC-Gel membrane could be a promising candidate material for corneal regeneration.
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Animals , Humans , Rabbits , Biocompatible Materials , Chemistry , Cells, Cultured , Chitosan , Chemistry , Cornea , Cell Biology , Corneal Injuries , Cross-Linking Reagents , Epithelium, Corneal , Cell Biology , Physiology , General Surgery , Gelatin , Chemistry , Guided Tissue Regeneration , Methods , Membranes, Artificial , Regeneration , Tissue Engineering , Methods , Tissue ScaffoldsABSTRACT
Objective To evaluate the therapeutic efficacy and treatment-related toxicity of stereotactic body radiation therapy(SBRT)in patients with medically inoperable stage Ⅰ/Ⅱ non-small cell lung cancer(NSCLC). Methods SBRT was applied to 30 patients, including clinically staged T1 ,T2(≤5cm)or T3(chest wall primary tumors only), N0, M0 ,biopsy-confirmed NSCLC. All patients were precluded from lobotomy because of physical condition or comorbidity. No patients developed tumors of any T-stage in the proximal zone. SBRT was performed with the total dose of 50 Gy to 70 Gy in 10 - 11 fractions during 12 - 15 days. prescription line was set onthe edge of the PTV. Results The follow-up rate was 100%. The number of patients who completed the 1-, and 2-year follow-up were 15, and 10, respectively. All 30 patients completed therapy as planned. The complete response(CR), partial response(PR)and stable disease(SD)rates were 37%, 53% and 3%, respectively. With a median follow-up of 16 months(range,4-36 months), Kaplan-Meier local control at 2 years was 94%. The 2-year overall survival was 84% and the 2-year cancer specific survival was 90%. Seven patients(23%)developed Grade 2 pneumonitis, no grade ＞ 2 acute or late lung toxicity was observed. No one developed chest wall pain. Conclusions It is feasible to deliver 50 Gy to 70 Gy of SBRT in 10 - 11 fractions for medically inoperable patients with stage Ⅰ / Ⅱ NSCLC. It was associated with low incidence of toxicities and provided sustained local tumor control.The preliminary investigation indicated the cancer specific survival probability of SBRT was high. It is necessary to perform similar investigation in a larger number of patients with long-term follow-up.
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ween WHO histological subtype and Masaoka clinical stage, and their combination is valuable for guiding postoperative treatment in thymoma.
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<p><b>BACKGROUND</b>Recently chemoradiotherapy becomes a standard treatment of un-resectable advanced non-small cell lung cancer (NSCLC) instead of radiotherapy alone. This study is to evaluate the clinical effect and toxicities of concurrent chemoradiotherapy in patients with stage III NSCLC after 2 cycles of induction chemotherapy with cisplatin-based regimens.</p><p><b>METHODS</b>Ninety-two patients with stage III NSCLC were divided randomly into two groups: forty-seven patients received concurrent chemoradiotherapy (chemoradiotherapy group), the other 45 patients received only radiotherapy (radiotherapy group). For both groups, the same radiation technic was given with the conventional fraction. The total dose was 60-65Gy/30-33Fr/6-6.5Wk. For the chemoradiotherapy group, the patients were also given with concurrent chemotherapy (navelbine 15-18mg/m² on the 1st and 8th day, cisplatin 60mg/m² on the 1st day).</p><p><b>RESULTS</b>The response rate in the chemoradiotherapy group was similar to that in the radiotherapy group (59.6% vs 51.5%, P > 0.05), but the complete response rate in the chemoradiotherapy group was significantly higher than that in the radiotherapy group (14.9% vs 6.7%, P < 0.05). The 1- and 2-year survival rates in the chemoradiotherapy group were similar to those in the radiotherapy group (65.9% and 42.5% vs 53.3% and 33.3%, P > 0.05). The 1- and 2-year local control rates in the chemoradiotherapy group were significantly higher than those in the radiotherapy group (63.8% and 53.2% vs 51.1% and 44.4%, P < 0.05). The incidences of grade III-IV radiation esophagitis and leukopenia in the chemoradiotherapy group were significantly higher than those in the radiotherapy group (21.2% and 12.7% vs 4.4% and 0, P < 0.01).</p><p><b>CONCLUSIONS</b>Concurrent chemoradiotherapy has the potential of improving the survival rate of stage III NSCLC, it can also increase the acute toxic effect, but all patients can tolerate this treatment regimen.</p>
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0.05).Conclusions:Concurrent chemoradiotherapy can be well tolerated even though the acute side-effects less than grade 2 were higher in concurrent chemoradiotherapy than other group.Immediate response was very encouraging in the concurrent group.There was no advantage in terms of survival rate in the concurrent group compared to the sequential group.
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Background and Purpose:In recent years,along with marked rise in the incidence of lung cancer,the incidence of brain metastasis from lung cancer has increased year by year.The main treatment strategy of lung cancer with brain metastasis is irradiation,while so far there are only few researches concerning chemotherapy combined with radiotherapy for these patients.The aim of this study is to evaluate the therapeutic effect,survival rate and toxicity of chemotherapy with VM_(26)+DDP regimen given concurrently with whole-brain radiotherapy in lung cancer with brain metastasis.Methods:From Sep.2000 to Oct.2001,forty-one patients with lung cancer with brain metastasis were divided randomly into two groups: 20 patients(14 male,6 female) received concurrent chemoradiotherapy(chemoradiotherapy group),the other 21 patients(14 male,7 female) received only radiotherapy(radiotherapy group).In the chemoradiotherapy group,the average age was 50 years with range 40 to 70 years,16 patients were non-small-cell lung cancer,4 patients were small-cell lung cancer.In the radiotherapy group,the average age was 52 years with range 40 to 73 years and 19 patients were non-small-cell lung cancer,2 patients were small-cell lung cancer.For both groups,the same radiation technique was given with conventional fraction.Radiotherapy was delivered by 6MV.Fractionations of 3Gy/fraction/day was delivered 10Gy/5 factions/week.The total dose was 30Gy/10Fr/2W.For chemoradiotherapy group,the patients were also given concurrent chemotherapy(VM_(26) 60mg/m~(2)/ day iv on days 1-3,cisplatin 60 mg/m~(2) iv on the 1~(st)day).Results:The response rate and complete response in the chemoradiotherapy group was significantly higher than that in the radiotherapy group(75% ?? 38.10%,P
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Objective Objective To evaluate the response,survival and toxicity of concurrent chemoradiotherapy for patients with inoperable esophageal cancer. Methods Eighty-eight patients with inoperable esophageal cancer were divided randomly into two groups, 43 patients in group R+C received chemoradiotherapy, while 45 patients in group R received radiotherapy only. For both groups, the same radiation technic was carried out by conventional fractionation, to a total dose of 60-65Gy/30-33Fr/6.0-6.5W. For group R+C patients, concurrent chemotherapy(5-Fu 500mg/d1-4,DDP 20mg/d1-4) was given. Results Complete response rate in group R+C was 33%,while in group R, it was 13% (P