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Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery, as demonstrated by the approval of patisiran for amyloidosis therapy in 2018. To illuminate the unique superiority of lipid nanovehicles in RNA delivery, in this review, we first introduce various RNA therapeutics, describe systemic delivery barriers, and explain the lipid components and methods used for lipid nanovehicle preparation. Then, we emphasize crucial advances in lipid nanovehicle design for overcoming barriers to systemic RNA delivery. Finally, the current status and challenges of lipid nanovehicle-based RNA therapeutics in clinical applications are also discussed. Our objective is to provide a comprehensive overview showing how to utilize lipid nanovehicles to overcome multiple barriers to systemic RNA delivery, inspiring the development of more high-performance RNA lipid nanovesicles in the future.
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BACKGROUND:Most of the silver coating materials prepared using active screen plasma technology in the past do not involve the nanotechnology field.The formed silver coating is in a"thin film"form,which is coated on the surface of the substrate,and the distribution of silver particles on the surface is uneven.Its long-term antibacterial ability is challenged. OBJECTIVE:To prepare nano silver coatings capable of being"buried"within stainless steel(SS)substrates using active screen plasma surface modification(ASPSM)and to observe antibacterial activity. METHODS:The nano-silver coating was prepared by ASPSM technique on stainless steel substrate.Three groups of coating samples were prepared by adjusting the bombardment time(1,2,and 4 hours),which were denoted as 1 h-Ag-ASPSM@SS,2 h-Ag-ASPSM@SS and 4 h-Ag-ASPSM@SS,respectively.The antibacterial activity of the coatings was analyzed by antibacterial ring test and Gram staining.The antibiotic coating samples of gentamicin combined with vancomycin were prepared by using stainless steel as substrate and were recorded as ACNs.Stainless steel,2 h-Ag-ASPSM@SS,and ACNs were inserted into Staphylococcus aureus or Pseudomonas aeruginosa suspension,respectively.The long-acting(84 days)antibacterial activity of the samples was analyzed by coating plate method.Bone marrow mesenchymal stem cells were co-cultured with stainless steel,2 h-Ag-ASPSM@SS,and ACNs,respectively.CCK-8 assay,dead/alive staining,and lactate dehydrogenase activity of cell supernatant were detected.Stainless steel,2 h-Ag-ASPSM@SS,and ACNs were taken after continuous exposure to Staphylococcus aureus suspension for 12 weeks.The amount of residual viable bacteria on the surface of the material was evaluated by spread plate method.Vancomycin drug sensitive disk method was used to evaluate the resistance of residual live bacteria on the surface of materials. RESULTS AND CONCLUSION:(1)With increasing bombardment time,the diameter of nano silver on the sample surface and the silver content in the coating gradually increased.Among them,the 2 h-Ag-ASPSM@SS exhibited the highest surface silver content while forming uniformly spherical nanoparticles.(2)Antibacterial ring test and Gram staining results demonstrated that compared with 1 h-Ag-ASPSM@SS and 4 h-Ag-ASPSM@SS,the 2 h-Ag-ASPSM@SS exhibited better inhibitory effect on Staphylococcus aureus and pseudomonas aeruginosa.After co-culturing with bacteria for 42 and 84 days,the number of viable bacteria on the spread plate method was significantly lower in the 2 h-Ag-ASPSM@SS group compared to the stainless steel and ACNs groups.After co-culturing with Staphylococcus aureus for 84 days and Pseudomonas aeruginosa for 42 days,the number of viable bacteria on the surface of the eluate from the ACNs group was higher than that of the stainless steel group.(3)CCK-8 assay,live/dead staining and lactate dehydrogenase activity of cell supernatant displayed that 2 h-Ag-ASPSM@SS did not have obvious cytotoxicity.ACNs showed obvious cytotoxicity.(4)After co-culture with Staphylococcus aureus for 12 weeks,the residual viable bacteria on the surface of 2 h-Ag-ASPSM@SS group was less than that of stainless steel group,and the residual viable bacteria on the surface of the ACNs group was more than that of stainless steel group.Compared with the stainless steel group,the sensitivity to vancomycin was significantly decreased in the ACNs group(P<0.001),and there was no significant change in sensitivity to vancomycin in 2 h-Ag-ASPSM@SS group(P>0.05).(5)The above results indicate that the silver nanoparticle coated stainless steel greatly improves the deposition efficiency of silver nanoparticles on the stainless steel surface and has long-lasting antibacterial properties and good cell compatibility.
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Objective:To evaluate the efficacy and safety of total aortic arch replacement in elderly patients with Stanford type A aortic dissection(TAAD).Methods:In this retrospective study, a total of 481 TAAD patients treated with total arch replacement in our hospital from January 2016 to January 2020 were divided into three groups: aged≤59 years, 60-69 years and ≥70 years.The differences between three groups in surgical method, extracorporeal circulation time, blocking time, circulatory time, stopping time, surgical time, ventilator use time, ICU time, hospitalization time, treatment rate of continued renal replacement, fatality rate, and cause of death were statistically analyzed and compared.Results:There were statistically significant differences in the stopping time between any two groups of the three groups(all P<0.05). The older the age, the shorter the circulatory arrest time.The difference of ventilator time and ICU time between ≤59 and 60-69 years was statistically significant( P<0.01). Patients with continuous renal replacement(CRRT)were 19.0%(71/373)in ≤59 years, 23.1%(18/78)in 60~69 years, and 26.7%(8/30)over 70 years.In-hospital mortality was 35/373(9.4%)in the group of ≤59 years old, 11/78(14.1%)in the group of 60~69 years old, and 5/30(16.7%)in the group of ≥70 years old.There was no death in patients undergoing type Ⅱ hybrid surgery. Conclusions:Age is one of the important death factors after total aortic arch replacement in TAAD patients.Total aortic arch replacement is an acceptable surgical method for elderly patients with TAAD.Hybridization may reduce hospitalization death in elderly patients.
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Objective:To compare the short-term clinical effect of arthroscopic and open reduction and internal fixation with Herbert screws in treatment of Mason type II radial head fractures.Methods:A retrospective case-control study was conducted to analyze the clinical data of 38 patients with unilateral radial head fractures (Mason type II) admitted to Shanghai Zhongye Hospital from January 2017 to December 2018, including 22 males and 16 females, aged from 20 to 65 years [(37.4±12.6)years]. Twenty patients were treated by arthroscopic reduction and internal fixation with Herbert screw (Group A), and eighteen by open reduction and internal fixation with Herbert screw (Group B). The operation time and fracture healing time were recorded. The visual analogue scale (VAS), elbow flexion and extension range, forearm rotation range and Mayo elbow function score were compared between the two groups before and at 1, 3, 6, and 12 months after operation. The results of Mayo elbow performance score (MEPS) and upper limb function assessment using the disabilites of the arm, shoulder, and hand (DASH) score were compared between the two groups. Complications including screw breakage or fracture displacement were also evaluated.Results:All patients were followed up for 12-14 months [(12.3±2.3)months]. There was no significant difference in operation time between the two groups ( P>0.05). The fracture healing time was (8.9±0.6)weeks in Group A and (8.7±0.6)weeks in Group B ( P>0.05). There was no significant difference in VAS between the two groups before operation ( P>0.05). The VAS was (4.8±0.5)points at 1 month after operation in Group A, lower than (6.0±0.7)points in Group B ( P<0.05). There was no significant difference in VAS between Group A and Group B at 3, 6, and 12 months after operation ( P>0.05). There was no significant difference in elbow flexion and extension range between the two groups before operation ( P>0.05). The elbow flexion and extension range in Group A was (110.4±3.8)° and (137.1±4.0)° at 1, 3 months after operation, which was significant greater than (90.6±4.7)° and (125.1±3.5)° in Group B ( P<0.05). There was no significant difference in elbow flexion and extension range between the two groups at 6 and 12 months after operation ( P>0.05). There was no significant difference in the range of forearm rotation between the two groups before operation ( P>0.05). The range of forearm rotation in Group A was (107.1±2.8)° and (138.1±2.9)° at 1, 3 months after operation, significantly greater than (95.5±3.9)°, (121.5±3.0)° in Group B ( P<0.05). There was no significant difference in forearm rotation range between the two groups at 6 and 12 months after surgery ( P>0.05). There was no significant difference in MEPS between the two groups before operation ( P>0.05). The MEPS in Group A was (50.4±3.8)points at 1 month after operation, higher than (40.6±4.7)points in Group B ( P<0.05). There was no significant difference in MEPS between the two groups at 3, 6, and 12 months after operation ( P>0.05). There was no significant difference in DASH score between the two groups before operation ( P>0.05). The DASH score was (57.1±2.8)points at 1 month after surgery in Group A, higher than (42.5±3.9)points in Group B ( P<0.05). The DASH score was not significantly different between the two groups at 3, 6, and 12 months after operation ( P>0.05). There was no screw loosening or fracture after operation, and one patient in each group had fracture displacement ( P>0.05). Conclusion:For Mason type II radial head fractures, arthroscopic Herbert screw fixation has the advantages of less trauma, less pain and faster functional recovery of the affected limb compared with open reduction and Herbert screw fixation.
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@#Objective To summarize the clinical feature and treatment experience of patients with acute type A aortic dissection involving coronary arteries. Methods The clinical data of 107 patients with acute type A aortic dissection involving coronary arteries, who received operation between June 5, 2012 and December 31, 2019 in our hospital, were analyzed retrospectively. There were 80 males and 27 females at age of 24-83 (49.8±11.2) years. Results The right coronary artery was involved in 65 patients, the left in 17 patients, and both coronary arteries in 25 patients. There were 48 (44.9%) patients undergoing coronary artery bypass grafting, 49 (45.8%) patients undergoing coronary artery plasty. Fifteen patients died 30 d after the operation, with a mortality rate of 14.0%. Patients with preoperative cardiogenic shock and postoperative acute renal failure had increased risk of death (P<0.05). Eighty-two (88.2%) patients were followed up for 2 to 71 months, and 1 patient had sudden cardiac death during the follow-up period. Conclusion Acute type A aortic dissection with coronary involvement is associated with high misdiagnosis rate and mortality rate. Taking proper strategies for surgical treatment of involved coronary arteries based on precise diagnosis may improve the prognosis of patients.
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BACKGROUND: The avulsion fracture of tibial Insertion of anterior cruciate ligament needs to be operated and fixed as early as possible. At present, the open reduction (absorbable screw, hollow screw, steel wire, and titanium cable) Is commonly used in the clinical treatment plan for internal fixation, which is more traumatic and has many postoperative complications. Arthroscopic reduction and elastic (suture) Internal fixation of anterior cruciate ligament fracture has the advantages of minimally invasive, clear surgical field, high fixation accuracy, few complications, good fracture reduction and healing, meeting the biomechanical requirements, and allowing rapid recovery of joint function, but also has the disadvantages of Insufficient strength, and osteotomy. OBJECTIVE: To compare the treatment efficacy of arthroscopic technique with Fiber Tape circular fixation and open reduction and fixation for the avulsion fracture of tibial Insertion of anterior cruciate ligament. METHODS: Thirty-two patients with tibial eminence fracture at Department of Orthopedics of Shanghai China Metallurgical Hospital from January 2017 to December 2018 were enrolled. All patients signed the informed consents and the study was approved by the Ethics Committee. The patients were divided into two groups based on surgical methods: Minimally Invasive group (n=17, arthroscopic reduction and Fiber Tape circular fixation) and open group (n=15, open reduction and hollow tension screw fixation). The operation time, blood loss, and postoperative complications were recorded. The range of motion of knee joint, Lysholm score, and International Knee Documenting Committee score before operation, 1 and 6 months after surgery were recorded. X-ray film was used to evaluate fracture healing. RESULTS AND CONCLUSION: (1) All patients were followed up for 6-13 months. (2) There were no significant differences in age composition, fracture type, cause of injury or preoperative score between two groups. (3) X-ray film showed satisfactory fracture reduction after operation. There were no neurological, vascular injury or fracture displacement after surgery. The fractures healed well after 6 months. (4) There was no significant difference In the operation time and postoperative complications between two groups. The blood loss showed significant difference between two groups (P=0.036). (5) The range of motion of knee joint at postoperative 1 month In both groups was significantly larger than that at baseline (P < 0.05). The range of motion of knee joint at postoperative 6 months was significantly larger than that at postoperative 1 month (P < 0.05). The range of motion of knee joint at postoperative 1 and 6 months in the minimally invasive group was significantly larger than that in the open group (P < 0.05). (6) The Lysholm and International Knee Documenting Committee scores at postoperative 1 month in both groups were significantly higher than those at baseline (P < 0.05). The scores at postoperative 6 months were significantly higher than those at postoperative 1 month (P < 0.05). The scores at postoperative 1 and 6 months in the minimally invasive group were significantly higher than those in the open group (P < 0.05). (7) These findings suggest that the patients in both groups after undergoing surgical methods had restored motion of range with time going. Compared with open fixation, arthroscopic reduction and Fiber Tape circular fixation for treating tibial eminence fracture has less blood loss, less trauma, shorter recovery time and higher functional recovery.
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BACKGROUND:The therapeutic regimen of intraarticular calcaneal comminuted fractures commonly selects plate and screw fixation. However, for case of posterosuperior calcaneal fracture, the weakness of achil es tendon stretch and plate screw fixation results in difficulty or maintenance of reduction. OBJECTIVE:To investigate the therapeutic effects of open reduction and internal fixation with steel screw and Steinmann pins for comminuted calcaneal intra-articular and posterosuperior fractures. METHODS:From December 2009 to December 2013, forty patients with fractures of comminuted calcaneal posterosuperior fractures were randomly divided into two groups. In the control group, patients were treated by open reduction and internal fixation by plate screw only. In the experimental group, patients were treated by open reduction and internal fixation by combination of plate screw and Steinmann pin. The Gissane and Bohler angles of the calcaneus were measured from lateral radiograph before and 4 weeks after surgery, and the MARYLAND score was assessed at the last fol ow-up. Gissane and Bohler angle and MARYLAND score were compared in each group and among different groups. RESULTS AND CONCLUSION:Al patients were fol owed up for 9-23 months. BOHLER and GISSANE angles were significantly bigger at 4 weeks after surgery compared with pre-treatment in both groups (P<0.05). BOHLER and GISSANE angles were significantly bigger in the experimental group than in the control group at 4 weeks after surgery (P<0.05). During final fol ow-up, the average score by MARYLAND Foot Score was 78 in the experimental group and 67 in control group, with their excellent and good rate of 80%and 73%. The excellent and good rate was significantly higher in the experimental group than in the control group (P<0.05). These data indicated that open reduction and internal fixation with combination of plate screw and Steinmann pin has better efficacy in treatment of the comminuted calcaneal intra-articular and posterosuperior fractures compared with plate and screw fixation alone. Their fixation is firm. Functional exercise can be performed earlier. Postoperative recovery of function of the affected limbs is better than plate and screw fixation alone.
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BACKGROUND:Scaffolds made of chitosan and its derivatives play an important role in cellmigration and axonal regeneration. Chitosan and its derivatives have good histocompatibility, which is easy to make stem cells grow on the surface, thereby having a more broad application prospect in the nerve tissue engineering. OBJECTIVE:To fabricate a thermosensitive hydrogel scaffold using chitosan/hydroxypropyltrimethyl ammonium chloride chitosan/sodium glycerophosphate (CS/HACC/GP), which is suitable for cellgrowth, and then, to observe the growth and proliferation of bone marrow mesenchymal stem cells on the scaffold. METHODS:Chitosan was modified using quaternary ammonium salt and confirmed by Fourier transform infrared spectroscopy. The chitosan and quaternary ammonium salt of chitosan was mixed at a ratio of 8:1 to successful y prepare stable CS/HACC/GP thermosensitive hydrogel scaffold. Then, the gel ing was observed, and biosafety test was conducted. RESULTS AND CONCLUSION:Fourier transform infrared spectroscopy showed the characteristic peak of quaternary ammonium groups. Cytotoxicity test showed that rat bone marrow mesenchymal stem cells cultured in hydrogel extracts had no toxicity. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test showed that hydrogel extracts exerted no significant effect on the increase in body weight, and the biological safety of the scaffold was good. Under the scanning electron microscopy, bone marrow-derived mesenchymal stem cells grew and proliferated normal y in the scaffold. The results confirmed that the CS/HACC/GP thermosensitive hydrogel scaffold was successful y prepared in the experiment, which is suitable for the growth and proliferation of bone marrow mesenchymal stem cells.
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BACKGROUND:In recent years, chitosan-based thermosensitive hydrogel, as scaffold materials, have received more and more attentions in the field of tissue repair because of good biocompatibility, biodegradability and drug-sustained release. OBJECTIVE:To explore the directed differentiation and growth of rat bone marrow mesenchymal stem cells on the quaternary chitosan thermosensitive hydrogel scaffold and to look for more ideal tissue engineering materials for the treatment of nervous system damage. METHODS:The thermosensitive hygrogel scaffold was prepared using hydroxypropyltrimethyl ammonium chloride chitosan (HACC) andβ-glycerophosphate (β-GP). The spatial structure of scaffold was observed by scanning electronic microscope. Effect of leaching liquor from the HACC/β-GP scaffold on the viability of bone marrow mesenchymal stem cells was detected by (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The albumin from bovine serum was combined with the scaffold, and the slow-release effect of the scaffold was detected by ultraviolet absorption spectrometry. Bone marrow mesenchymal stem cells were incubated onto the compound scaffold at 3 passages. The adhesion, growth and differentiation of bone marrow mesenchymal stem cells on the compound scaffold were observed by the scanning electron microscope. Neuron-specific enolase was detected by immunofluorescence. RESULTS AND CONCLUSION:The porosity and thermal sensitivity of HACC/β-GP scaffold and slow-release effect of glial cellline-derived neurotrophic factor were apparent. The results of MTT showed that the compound scaffold cannot take apparent negative effects to the proliferation of bone marrow mesenchymal stem cells. After inoculation, bone marrow mesenchymal stem cells permeated the porous structure of the scaffold and adhered to the scaffold. Under the role of glial cellline-derived neurotrophic factor, bone marrow mesenchymal stem cells showed neuron-like cellmorphology and cells co-cultured with the compound scaffold expressed the marker of neurons, neuron-specific enolase. Under the role of slow-release glial cellline-derived neurotrophic factor, bone marrow mesenchymal stem cells can grow wel in vitro and differentiate into neuron-like cells on the HACC/β-GP scaffold.