Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis. However, nearly all nucleic acid delivery systems developed for atherosclerosis necessitate injection, which results in rapid elimination and poor patient compliance. Consequently, oral delivery strategies capable of targeting atherosclerotic plaques are imperative for nucleic acid therapeutics. Herein we report the development of yeast-derived capsules (YCs) packaging an antisense oligonucleotide (AM33) targeting microRNA-33 (miR-33) for the oral treatment of atherosclerosis. YCs provide stability for AM33, preventing its premature release in the gastrointestinal tract. AM33-containing YCs, defined as YAM33, showed high transfection in macrophages, thus promoting cholesterol efflux and inhibiting foam cell formation by regulating the target genes/proteins of miR-33. Orally delivered YAM33 effectively accumulated within atherosclerotic plaques in ApoE ^-/- mice, primarily by transepithelial absorption via M cells in Peyer's patches and subsequent translocation via macrophages through the lymphatic system. Inhibition of miR-33 by oral YAM33 significantly delayed the progression of atherosclerosis. Moreover, oral treatment with YCs co-delivering AM33 and atorvastatin afforded significantly enhanced anti-atherosclerotic effects. Our findings suggest that yeast-based microcapsules represent an effective carrier for oral delivery of nucleic acids, either alone or in combination with existing drugs, offering a promising approach for precision therapy of atherosclerotic diseases.

OBJECTIVE:External fixators and plate internal fixation are commonly used treatments for comminuted distal radius fractures,each with its own advantages and disadvantages in clinical practice. To systematically evaluate the clinical efficacy and safety of external fixator and plate internal fixation in the treatment of comminuted distal radius fractures,and to provide a basis for the development of guidelines for the diagnosis and treatment of distal radius fractures with integrated traditional Chinese and Western medicine. METHODS:PubMed,Web of Science,Embase,Cochrane Library,China National Knowledge Infrastructure,China Biomedical Literature Database,VIP,andWanFang databases were systematically searched to include randomized controlled trials on external fixators and internal plate fixation for the treatment of comminuted distal radial fractures published from October 2013 to October 2023. The literature was screened according to the inclusion and exclusion criteria. Review Manager was used for literature quality evaluation and meta-analysis.RESULTS:(1) Eight articles were included,including 4 in Chinese and 4 in English,with a total sample size of 648 cases,including 328 cases in the external fixation stent group and 320 cases in the internal fixation plate group. (2) At 3 months after operation,the internal fixation plate group was superior to the external fixation stent group in the range of dorsal extension,palmar flexion and supination. At 12 months after operation,the grip strength,palmar inclination,palmar flexion,pronation and supination in the internal fixation plate group were better than those in the external fixation stent group. The postoperative infection in the internal fixation plate group was better than that in the external fixation stent group,and there was no statistical difference in other outcome indicators.CONCLUSION:Eight evidences showed that in the choice of treatment for comminuted distal radius fracture,both external fixation stent and incision plate internal fixation had good therapeutic effect,and plate internal fixation was better than other factors. However,for some special patients with highly severe comminuted distal radius fractures,poor bone quality,severely contaminated open fractures,and soft tissue swelling that did not allow incision surgery,external fixation was the first choice. The results of this study have limitations,and more high-quality,large-sample,multi-center randomized controlled trials are needed in the future,emphasizing the observation of long-term efficacy and other secondary indicators,and supplementing and optimizing the current research results.

OBJECTIVE:External fixators and plate internal fixation are commonly used treatments for comminuted distal radius fractures,each with its own advantages and disadvantages in clinical practice. To systematically evaluate the clinical efficacy and safety of external fixator and plate internal fixation in the treatment of comminuted distal radius fractures,and to provide a basis for the development of guidelines for the diagnosis and treatment of distal radius fractures with integrated traditional Chinese and Western medicine. METHODS:PubMed,Web of Science,Embase,Cochrane Library,China National Knowledge Infrastructure,China Biomedical Literature Database,VIP,andWanFang databases were systematically searched to include randomized controlled trials on external fixators and internal plate fixation for the treatment of comminuted distal radial fractures published from October 2013 to October 2023. The literature was screened according to the inclusion and exclusion criteria. Review Manager was used for literature quality evaluation and meta-analysis.RESULTS:(1) Eight articles were included,including 4 in Chinese and 4 in English,with a total sample size of 648 cases,including 328 cases in the external fixation stent group and 320 cases in the internal fixation plate group. (2) At 3 months after operation,the internal fixation plate group was superior to the external fixation stent group in the range of dorsal extension,palmar flexion and supination. At 12 months after operation,the grip strength,palmar inclination,palmar flexion,pronation and supination in the internal fixation plate group were better than those in the external fixation stent group. The postoperative infection in the internal fixation plate group was better than that in the external fixation stent group,and there was no statistical difference in other outcome indicators.CONCLUSION:Eight evidences showed that in the choice of treatment for comminuted distal radius fracture,both external fixation stent and incision plate internal fixation had good therapeutic effect,and plate internal fixation was better than other factors. However,for some special patients with highly severe comminuted distal radius fractures,poor bone quality,severely contaminated open fractures,and soft tissue swelling that did not allow incision surgery,external fixation was the first choice. The results of this study have limitations,and more high-quality,large-sample,multi-center randomized controlled trials are needed in the future,emphasizing the observation of long-term efficacy and other secondary indicators,and supplementing and optimizing the current research results.

Uncontrolled and persistent inflammation is closely related to numerous acute and chronic diseases. However, effective targeting delivery systems remain to be developed for precision therapy of inflammatory diseases. Herein we report a novel strategy for engineering inflammation-accumulation nanoparticles via phenolic functionalization. Different phenol-functionalized nanoparticles were first developed, which can undergo in situ aggregation upon triggering by the inflammatory/oxidative microenvironment. Phenolic compound-decorated poly (lactide-co-glycolide) nanoparticles, in particular tyramine (Tyr)-coated nanoparticles, showed significantly enhanced accumulation at inflammatory sites in mouse models of colitis, acute liver injury, and acute lung injury, mainly resulting from in situ cross-linking and tissue anchoring of nanoparticles triggered by local myeloperoxidase and reactive oxygen species. By combining a cyclodextrin-derived bioactive material with Tyr decoration, a multifunctional nanotherapy (TTN) was further developed, which displayed enhanced cellular uptake, anti-inflammatory activities, and inflammatory tissue accumulation, thereby affording amplified therapeutic effects in mice with colitis or acute liver injury. Moreover, TTN can serve as a bioactive and inflammation-targeting nanoplatform for site-specifically delivering a therapeutic peptide to the inflamed colon post oral administration, leading to considerably potentiated in vivo efficacies. Preliminary studies also revealed good safety of orally delivered TTN. Consequently, Tyr-based functionalization is promising for inflammation targeting amplification and therapeutic potentiation of nanotherapies.

Cerebrolysin is an aqueous mixture of amino acids extracted from porcine brain, and mainly composed of 85% free amino acids and 15%small peptides. Cerebrolysin increase the metabolism of amino acids and glucose transport in the brain, improve the anti-anoxia ability of cells, and to enhance the brain's resistance to various types of malignant stimulation like stress and damage. Cerebrolysin can also promote synapse formation, induce neuronal differentiation, and help reverse brain injury. Because of its efficacy and safety, cerebrolysin has been widely used in the pediatric clinical practice, and primarily to treat neonatal hypoxic ischemic encephalopathy, childcerebral palsy, hyperactivity disorder, speech communication disorders, etc.The clinical symptoms were improved to some extent after the treatment of cerebrolysin. The recovery of consciousness, enhancement of comprehensionand memory, and improvement of the extremity motor function were observed. The treatment of cerebrolysincan not only enhance the cure rate, but also reduce the incidence of sequelae. This paper systematically summarized the clinical application of cerebrolysin in the pediatric population and relevant preclinical studies, to provide more guidance for clinical application of cerebrolysin in the treatment of pediatric diseases.

Objective Systematic evaluation of cerebrolysin in the treatment of neonatal hypoxic -ischemic encephalopathy.Methods Computer search Cochrane Library, EMBase, PubMed, Chinese Journal Full-text Database (CNKI), Chinese Biomedical Literature Database (CBM), Wanfang Database ( each database retrieval time from its creation to May 2016 ) About cerebrolysin Randomized controlled clinical trial of neonatal hypoxic -ischemic encephalopathy.According to the inclusion and exclusion criteria of the literature, the methodological quality of the included research was evaluated and the data were extracted.Metadata was analyzed by RevMan 5.3 software.Results A total of 41 RCT patients were enrolled, with a total of 3695 patients, the experimental group was 1932 cases, the control group was 1763 cases.Meta analysis showed, the efficacy of cerebrolysin in the treatment of neonatal hypoxic-ischemic encephalopathy was significantly higher than that in the control group [OR=3.85, 95% CI (3.15,4.70), P<0.000001], for the impact of clinical symptoms, the number of primitive reflexes of neonatal hypoxic-ischemic encephalopathy in the treatment group was significantly higher than that in the control group [MD=-1.22, 95% CI ( -2.06,-0.38), P=0.004], muscle tension recovery days[MD=-1.69, 95% CI ( -1.80,-1.58), P<0.00001], conscious state recovery days[MD=-1.32, 95% CI ( -2.25,-0.40), P=0.005], seizure recovery days [MD=-2.36, 95% CI ( -3.70, -1.03), P =0.0005], and other indicators were shorter than the control group, the difference between the experimental group and the control group was statistically significant.Conclusion Cerebrolysin havean effective in treating HIE.

Cerebrolysin is an aqueous mixture of amino acids extracted from porcine brain.Cerebrolysin, contains a variety of amino acids and low molecular weight peptides, are permeable to the blood-brain barrier and blood-ocular barrier and can directly act on neurons in the CNS.As amino acid-based neuroprotective reagents, cerebrolysin can improve the neuronal metabolism, promote synapse formation and induce neuronal differentiation, and thus elicit neuroprotective efffectagainst insults such as ischemia , neurotoxins and so on.Cerebrolysin is clinicly used to treat eye diseases such as traumatic eye damage, glaucoma, optic atrophy ect.This paper systematically summarizes the studies on preclinical and clinical application of cerebrolysin in ophthalmology.