Stable Blood Circulation Research Articles

Role of endothelial Raptor in abnormal arteriogenesis after lower limb ischaemia in type 2 diabetes.

Proper arteriogenesis after tissue ischaemia is necessary to rebuild stable blood circulation; nevertheless, this process is impaired in type 2 diabetes mellitus (T2DM). Raptor is a scaffold protein and a component of mammalian target of rapamycin complex 1 (mTORC1). However, the role of the endothelial Raptor in arteriogenesis under the conditions of T2DM remains unknown. This study investigated the role of endothelial Raptor in ischaemia-induced arteriogenesis during T2DM. Although endothelial mTORC1 is hyperactive in T2DM, we observed a marked reduction in the expression of endothelial Raptor in two mouse models and in human vessels. Inducible endothelial-specific Raptor knockout severely exacerbated impaired hindlimb perfusion and arteriogenesis after hindlimb ischaemic injury in 12-week high-fat diet fed mice. Additionally, we found that Raptor deficiency dampened vascular endothelial growth factor receptor 2 (VEGFR2) signalling in endothelial cells (ECs) and inhibited VEGF-induced cell migration and tube formation in a PTP1B-dependent manner. Furthermore, mass spectrometry analysis indicated that Raptor interacts with neuropilin 1 (NRP1), the co-receptor of VEGFR2, and mediates VEGFR2 trafficking by facilitating the interaction between NRP1 and Synectin. Finally, we found that EC-specific overexpression of the Raptor mutant (loss of mTOR binding) reversed impaired hindlimb perfusion and arteriogenesis induced by endothelial Raptor knockout in high-fat diet fed mice. Collectively, our study demonstrated the crucial role of endothelial Raptor in promoting ischaemia-induced arteriogenesis in T2DM by mediating VEGFR2 signalling. Thus, endothelial Raptor is a novel therapeutic target for promoting arteriogenesis and ameliorating perfusion in T2DM.

Application Effects of Light Lumbar Anesthesia and Nerve Block Anesthesia in Elderly Hip Joint Surgery

Objective: To analyze the application effects of light lumbar anesthesia and nerve block anesthesia in elderly hip joint surgery. Methods: A total of 40 patients indicated for hip joint surgery from February 2021 to February 2022 were randomly divided into the control group and the observation group, each with 20 patients. The control group received nerve block anesthesia and the observation group was given light lumbar anesthesia. Results: Based on the results, the anesthetic effect in the observation group was better than that in the control group (P < 0.05), the difference was statistically significant. Conclusion: Compared with nerve block anesthesia, light lumbar anesthesia can achieve better analgesic effects and stable blood circulation in elderly patients undergoing hip joint surgery.

Dynamic precise dual-drug-backboned nano-prodrugs for selective chemotherapy

To achieve an ideal drug delivery platform with precise composition and high tumor selectivity, the PEGylated dual-drug backboned prodrug was synthesized via the copolymerization between diamine monomer of ortho ester and cisplatin- demethylcantharidin conjugate (Pt(IV)-1), and then terminated by mPEG550-active ester. The amphipathic prodrug could self-assemble into nano-prodrugs, which endowed the precise structure and high drug loading. Moreover, the nano-prodrugs exhibited physicochemical stability at physiological pH (7.4) for stable blood circulation, DePEGylation and dynamic size change for selective tumor accumulation and enhanced cellular internalization at tumoral extracellular pH (6.8), and efficient drug release for synergetic apoptosis and cytotoxicity at tumoral intracellular pH (5.0)/glutathione. Thus, the precise dual-drug backboned nano-prodrugs with detachable PEGylation, dynamic size change and efficient drug release could be potentially translated for clinically selective cancer treatment. Statement of significanceFew nanomedicines have been clinically used for cancer treatment and little progress has been made in the last decades due to the unprecise composition and unsatisfactory tumor selectivity. Herein, the PEGylated dual-drug backboned nano-prodrugs were successfully constructed by rational design and endowed the defined structure, precise drug ratio, extraordinary high drug loading and reduction/pH dual sensitivity. The nano-prodrugs further exhibited the stable storage and blood circulation through PEGylation and low critical micelle concentration, enhanced tumor accumulation and cellular uptake via extracellular DePEGylation and dynamic size translation, and synergetic cytotoxicity via intracellular efficient drug release, respectively. This study can open a new avenue for easy industrial manufacture and quality control, and highly selective chemotherapy appealing for clinical translation..

Dynamic methotrexate nano-prodrugs with detachable PEGylation for highly selective synergistic chemotherapy

To promote the highly selective synergistic chemotherapy, the pH-ultra-sensitive dynamic methotrexate nano-prodrugs with detachable PEGylation were successfully prepared via facile method, and the synergistic nanodrugs could be further constructed through encapsulating Doxorubicin (DOX) following the self-assembly process. The nano-prodrugs exhibited the low critical micelle concentration (CMC), negative zeta potential and stability for 5 days in PBS and FBS at physiological pH (7.4) for stable blood circulation, DePEGylation and dynamic size change at tumoral extracellular pH (6.8) for improved tumor accumulation and cellular internalization, and efficiently synergistic drug release at tumoral intracellular pH (5.0) for enhanced tumor apoptosis and cytotoxicity. Moreover, in vivo experiment suggested that the synergistic nanodrugs could significantly improve tumor accumulation and restrain tumor growth while decreasing adverse effects. Therefore, the dynamic methotrexate nano-prodrugs with detachable PEGylation are easy to clinically transform for highly selective synergistic chemotherapy.

A Modified Design of the Pectoralis Major Myocutaneous Flap for Reconstruction of Head and Neck Defect.

Even though the pectoralis major myocutaneous flap (PMMF) still has an important role in the free flaps ear, it is reported to have drawbacks such as the limited cephalad extension and high incidence of total or partial flap necrosis. Various modifications have been attempted to augment the limited cephalad extension and a stable blood supply.The aim of this study is to describe a modified design of the skin paddle and preparation of the PMMF, to achieve stable blood circulation and sufficient pedicle length. The priority skin paddle is the medial part for its stable blood supply, and the lateral margin should be adjusted as needed. During the harvesting, the lateral thoracic artery (LTA) is preserved to protect the perforating branches, and the anterior sheath of the rectus abdominis muscle is used as a suture margin to prevent damage of the thin muscle of the PMMF. The skin paddles in this study are larger than those previously reported. All of the 21 patients in our study, the skin paddles show complete survival with no partial necrosis of skin paddle, fistula, or wound dehiscence.It is worthwhile to consider and preserve the LTA as a major contributor to a lateral and distal PMMF. This study would be useful in future and preparation of the PMMF in head and neck reconstruction.

Sequentially dynamic polymeric micelles with detachable PEGylation for enhanced chemotherapeutic efficacy

To achieve enhanced cancer therapy, a sequentially dynamic polymeric drug delivery system (ortho ester-linked PEGylated poly(disulfide)s-based micelle-doxorubicin (PS-g-OEMPEG-DOX)) is successfully constructed. The PEGylated micelle can keep stable in sodium dodecyl sulfate (SDS) solution at pH 7.4, but be prone to DePEGylation and dynamic size changes via the hydrolysis of ortho ester linkages in side chains at tumoral extracellular pH value (6.5). Moreover, the micelle can rapidly release DOX via the cleavage of poly(disulfide)s in backbone at intracellular reductive milieu (10 mmol/L of dithiothreitol (DTT)). The dynamic micelle with detachable PEGylation achieves the stable blood circulation, improved cellular uptake and cytotoxicity, stronger in vitro penetration and inhibition of tumoral multicellular spheroids, and significant in vivo tumor accumulation and inhibition while decreasing side effects. Thus, the sequentially dynamic polymeric micelle with detachable PEGylation can be considered as a promising and effective drug delivery system in cancer therapy.

The role of human serum albumin therapy in the post-operative management of patients with hepatocellular carcinoma associated with cirrhosis

Objective To determine the role of human serum albumin therapy in the post-operative management of patients with hepatocellular carcinoma (HCC) associated with cirrhosis.Methods Between January 2011 and December 2012,we treated 171 consecutive cirrhotic patients with HCC.88 patients were treated with 5％ human serum albumin for 48 hours followed by 20％ human serum albumin in the post-operative period (the observer group) ; 81 patients were only treated with 20％ human serum albumin during the same time duration (the control group).The prognosis,complications,average amount of human serum albumin and plasma used as well as the in-hospital stay were observed.Results There were no deaths or major complications in either of these 2 groups.After treatment,the observer group was lower than the control group in the amount of intravenous fluid infused,the volume of peritoneal drainage,the amount of human serum albumin and plasma used as well as the mean post-operative hospitalization days (P ＜ 0.05).At the same time,the daily urine output,the central venous pressure and the mean arterial pressure within 48 hours after surgery were higher in the observer group than the control group.Furthermore the observer group had a smoother post-operative recovery in liver function,and the difference was significant between the two groups (P ＜ 0.05).Conclusion Not only did treatment with 5 ％ and 20％ human serum albumin gave the advantages of a more stable blood circulation,better organ perfusion and improved liver function recovery but it also reduced the amount of consumption of human serum albumin and plasma and shortened the hospital stay. Key words: Hepatocellular carcinoma; Liver function; Albumin; Liver neoplasm; Cirrhosis

New Method of Preparing a Pectoralis Major Myocutaneous Flap with a Skin Paddle that Includes the Third Intercostal Perforating Branch of the Internal Thoracic Artery

Although the use of free flaps has become a major option for head and neck reconstruction, the pectoralis major myocutaneous flap still plays an important role because of its advantages and its convenience as a pedicle flap located adjacent to head and neck lesions. However, there remain two problems with the pectoralis major myocutaneous flap, namely, the difficulty in preparing a small, thin skin paddle with stable blood circulation for small defects and, particularly for female cases, sacrifice of the breast. The authors report a new method of preparing a pectoralis major myocutaneous flap to solve these problems. A skin paddle is designed just above the third intercostal perforating branch of the internal thoracic artery. The pectoralis major myocutaneous flap, including the muscular branch of the third intercostal perforating branch in its muscle, is elevated. The pectoralis major myocutaneous flap is moved to the reconstruction site through the subclavian route. This method was used for 11 cases with small defects in the head and neck caused by lesions. Slight marginal necrosis was observed in one case, but the other skin paddles took completely. There was no infection or fistula formation, and almost satisfactory functional results were obtained in all cases. Deformity in donor sites that included a breast was also minimal. With this method, it was possible to prepare the pectoralis major myocutaneous flap using a small, thin skin paddle with stable blood circulation. Breast deformation, particularly in female cases, was also kept to a minimum.

Preparation and in vivo imaging of PEG-poly(L-lysine)-based polymeric micelle MRI contrast agents

A polymeric micelle drug carrier system was applied to the targeting of an MRI (magnetic resonance imaging) contrast agent. A block copolymer, PEG- b-poly(L-lysine), was used for conjugation of gadolinium ions through chelating moieties, DOTA. The DOTA moieties were successfully conjugated to all primary amine groups of the lysine residues. The obtained block copolymer, PEG- b-poly(L-lysine-DOTA), formed a polymeric micelle. The polymeric micelle structure was maintained even after partial gadolinium chelation (∼ 40%) to the DOTA moieties. The prepared polymeric micelle MRI contrast agent was injected into a mouse tail vein at a dose of 0.05 mmol Gd/kg. The polymeric micelle-based MRI contrast agent exhibited stable blood circulation. A considerable amount (6.1 ± 0.3% of ID/g of the polymeric micelle) was found to accumulate at solid tumors 24 h after intravenous injection by means of the EPR effect. An MRI analysis revealed that the signal intensity of the tumor was enhanced 2.0-fold by the use of this contrast agent.

The post-burn elbow medial flexion scar contracture treatment with trapeze-flap plasty

A medial flexion elbow contracture is characterized by the presence of a fold which has a semi-lunar shape, the sheets of which are scars. The shortage in skin length and the excess in width occurs in the sheets. To estimate the size and form of length deficiency in the fold is the section from the top of the fold to the rotation axis of the joint. As a rule, the wound receives a trapeze form. To convert the sheets of the fold into trapeze-shaped flaps, several radial cross-sections from the tops of the fold to joint rotation axis are used. The flaps are mobilized with the full fat layer, and then transposed toward one another causing tension, therefore, covering the wound on the flexion surface of the joint. Flaps and the adjacent skin, displaced forward from lateral and back surfaces of the joint, participate in wound coverage. Trapezoid flaps have a wide end, stable blood circulation; they do not undergo rotation, therefore, do not undergo necrosis. Contractures are eliminated in full without relapse. As a rule, in all 35 patients the functional outcome was perfect.

A New Modified Forked Flap With Subcutaneous Pedicles for Adult Cases of Bilateral Cleft Lip Nasal Deformity

In adult cases of bilateral cleft lip nasal deformity, an esthetically satisfying result can not be obtained only by manipulation inside the nose with the nasal tip pointing upward. The nasal tip should be made in a more anterior direction for nasal esthetic improvement. Additional tissue beyond the nose is needed, and the forked flap is a useful method in such cases. However, the blood circulation of long and narrow flaps containing the scar, especially after open rhinoplasty, is unstable. We have developed a new long and narrow forked flap that has a more stable blood circulation. The forked flap was made using two subcutaneous pedicles attached to the periphery of the each flap. We applied this flap to five adult cases of bilateral cleft lip nasal deformity. Four of the cases had the scar associated with the flying bird incision, and one case required no treatment after the primary repair. All the flaps took without signs of partial necrosis. In all cases, the nasal tip was projected forward with adequate columella elongation, and the profile was esthetically improved. In the final stage of correction for adult cases of bilateral cleft lip nasal deformity, this method, making maximum use of the tissue containing the scar in not only the white lip but also the vermilion, is very effective. It is very important to obtain nasal esthetic improvement for the adult patient with bilateral cleft lip nasal deformity.