Disrupted bone morphogenetic protein type 2 receptor (BMPR2) signaling in endothelial cells drives pulmonary arterial hypertension (PAH). However, targeted recovery of this signaling pathway by lipid nanoparticles (LNPs) has not been explored as a therapy. Here, we employed Design of Experiments to optimize the delivery efficiency of LNPs targeting pulmonary endothelial cells developed by our laboratory, resulting in a remarkable 35-fold increase in a simplified three-component formulation without helper lipids. Administration of BMPR2 mRNA LNPs effectively reversed established PAH in two experimental rat models (monocrotaline or SU5416-hypoxia) by reversing pulmonary vascular remodeling. Specifically, BMPR2 mRNA LNPs replenished the expression of BMPR2 protein and subsequently activated downstream pathways, as confirmed by elevated levels of p-SMAD1/5/9 and ID1 proteins. The relief of pulmonary arterial occlusion was demonstrated by thinned pulmonary arterial media and decreased proportion of full muscularized vessels. Alleviation of right ventricular hypertrophy was indicated by declined Fulton index, the cross-sectional area of right ventricular cardiomyocytes as well as collagen deposition. Effective recovery of right ventricular function was evidenced by increased pulmonary artery flow acceleration time/pulmonary artery flow ejection time ratio. These findings underscore the potential of restoring BMPR2 signaling through pulmonary endothelial cell-specific LNPs for treating PAH.

Objective To explore the effect of melatonin(MT)-modified PEEK implant assisted by polydopamine(PDA)coating on osteointegration in osteoporotic rats.Methods MT was adhered to PEEK implants with PDA coating as carrier.The physicochemical properties of the materials were analyzed by SEM image,water contact angle,FTIR and protein adsorption experiment.OVX-rBMSCs were inoculated on the surface of PEEK sheet and cultured.The cytoskeleton was stained and cell adhesion morphology was observed.Cell proliferation activity was evaluated by CCK-8 assay;key enzyme activities for osteogenic differentiation were analyzed by ALP stai-ning,and expression levels of osteoblast-related genes COL-1,Runx2,OPN,OCN,BMP-2 and ALP were detected by quantitative real-time PCR.In addition,implants were implanted into the femur of osteoporotic rats and bone volume on the implant surface was de-tected and quantified by Micro-CT.Results MT was successfully loaded on PEEK;the cell adhesion was better,and the proliferation activity and osteogenic differentiation ability were significantly higher than those of control group(P＜0.01).In the rat osteoporosis mod-el,there was more new bone formation around the modified PEEK implant(P＜0.01).Conclusion MT-modified PEEK implants have excellent biocompatibility and improve osteointegration in an osteoporotic environment.

In order to understand the prevalence and genetic variation of H9N2 subtype avian influ-enza virus in Shandong,a total 492 tracheal and lung tissue samples collected from chicken farms with respiratory symptoms in partial areas in Shandong were detected by H9 subtype AIV real-time RT-PCR,and the positive samples were inoculated with chicken embryos for two generations.Whole genome sequences of the positive strains by applying Illumina Miaseq platform,and genetic evolution and mutation at positions associating with viral pathogenicity and transmissibility were analyzed.The results showed that there were 72 samples were positive for H9 subtype AIV among the 492 samples,with a positive rate of 14.63％.Thirty-four strains of H9 subtype AIV were ob-tained from the positive samples after passing through chicken embryo,meanwhile,the 34 isolates were all H9N2 subtype AIV by whole genome sequencing analysis.By analyzing the evolutionary tree of HA and NA genes,HA and NA genes of the 34 H9N2 AIV strains belonged to Y280-like branch and F/98-like branch,respectively.Meanwhile,based on above branches,there were obvious time node subbranch,which one was"isolates before 2013",another one was"isolates after 2013".The HA cleavage sites of thirty-four H9N2 strains were all 325PSRSSR↓GLF333,which met the se-quence characteristics of the lowly pathogenic avian influenza virus,and the HA receptor binding site 226 amino acid was leucine,which had the characteristics of blinding to a-2,6 mammalian sialic acid receptors.Among the internal amino acid sites that are key to mammalian adaptation,all strains had an I368V mutation in the PB1 gene that enhanced viral transmissibility in mammals and the PB2 genes of some strains were mutated to enhance the mammalian adaptation of I292 V and A588 V.The above results illustrated that the H9N2 subtype AIV gene segments in Shandong have different degrees of recombination and gene variation,so it is necessary to strengthen the monito-ring of virus variation.

Humans ; SARS-CoV-2 ; COVID-19 ; Antibodies ; Antibodies, Viral/therapeutic use* ; Antibodies, Neutralizing/therapeutic use*

Objective To investigate the characteristics of liver deformation and changes in abdominal vascular diameter under artificial pneumoperitoneum based on CT images,and also to reveal the impact of intestinal adhesion on these characteristics.Methods A retrospective study was conducted on 61 patients who underwent abdominal CT scan and artificial pneumoperitoneum CT.Eight cases did not meet the inclusion criteria.The sample included 41 patients with postoperative intestinal adhesion(POIA)and 12 patients without POIA.A three-dimensional post-processing software was used to quantify the gas volume,liver volume,liver surface area,and lumen of the abdominal aorta,inferior vena cava,and portal vein on CT images of patients who underwent abdominal CT scan and artificial pneumoperitoneum CT.The measured indices were compared before and after artificial pneumoperitoneum in all patients,and the impact of intestinal adhesion on the aforementioned indices was evaluated.Results At equivalent levels of pneumoperitoneum pressure,no statistically significant difference was observed in the quantity of gas in the abdominal cavity between patients with and without POIA(P=0.753).In the absence of pneumoperitoneum,POIA patients exhibited a significantly higher liver volume than non-adhesion patients(P＜0.01).Following the application of artificial pneumoperitoneum pressure,both liver volume and liver surface area were reduced in all patients,with a more pronounced decrease in POIA group(P=0.003,P=0.002).In addition,the reductions in the internal diameters of the inferior vena cava at three locations and the portal vein position 1 were also observed in all patients(P＜0.05).Notably,the POIA group exhibited more significant decrease in the internal diameters of inferior vena cava position 1 and the portal vein position 1(P=0.022,P=0.038).No significant differences were observed in the changes of internal diameter of other blood vessels or in the intergroup comparison.Conclusion Artificial pneumoperitoneum can reduce the volum,the surface area of liver,and the inner diameter of some abdominal vessels,which provides a scientific basis for navigation and real-time correction in laparoscopic abdominal surgery for patients,especially for patients with POIA.

Marinesco-Sj?gren syndrome (MSS), also known as hereditary ataxia-dwarf-mental retardation syndrome, is a rare autosomal recessive ataxia syndrome. This article reviews the recent advance in clinic characteristics, pathogenic gene mutation sites, pathogenesis and clinic diagnosis and treatment of MSS, in order to improve clinicians' understanding of the disease and diagnosis and treatment level, and reduce the missed diagnosis and misdiagnosis of the disease.

Sialidosis is a rare lysosomal storage disease caused by NEU1 gene mutation at 6p21.33. It is characterized by myoclonic, ataxia, epilepsy, and decreased vision. A pair of twins with sialidosis type 1 are reported to enrich clinicians ′ understanding of the disease, so as to improve the diagnosis and treatment. The proband was a 16-year-old male. The main symptom was intermittent limb involuntary trembling for 2 years, with paroxysmal loss of consciousness. Fundus examination showed cherry-red spots. His twin brother had similar symptoms, but the overall performance was mild. Whole exome sequencing results showed that both patients carried compound heterozygous mutations of c.239C>T (p.P80L) and c.803A>G (p.Y268C) in NEU1 gene, which were from their normal phenotype mother and father.

Objective　To investigate the protective effect and mechanism of the derivative NIM811 on hypoxia/reoxygenation injury of rat hippocampal neuron (HT22) induced by sodium disulfite (Na2S2O4).Methods　The hypoxia/reoxygenation cell model was prepared with mouse HT22 cultured cells.The experiment was divided into normal control group,Na2S2O4 group,Na2S2O4+NIM811 group,and NIM811 group.Cell survival rate was detected by CCK-8,flow cytometry was used to detect apoptosis,mitochondrial membrane potential was detected by JC-1 reagent,calcium ion level in mitochondria was observed by Rhod-2 AM,and reactive oxygen species (ROS) was detected by DCFH-DA method.Results　Compared with the Na2S2O4 group,after NIM811 treatment:(1)Cell activity increased by 38% (P<0.01);(2)Apoptosis decreased by 27% (P<0.01);(3)Mitochondrial membrane potential increased (P<0.01);(4)The level of calcium ions in the mitochondria decreased (P<0.01);(5)The level of reactive oxygen species (ROS) decreased (P<0.01).Conclusion　NIM811 has a protective effect on the hypoxia/reoxygenation injury of mouse hippocampal neurons caused by Na2S2O4.The mechanism may be related to the maintenance of mitochondrial homeostasis and inhibition of cell apoptosis.NIM811 has therapeutic potential for future clinical treatment of ischemic stroke.

Objective:To investigate the effects of anterolateral wide pedicled double dynamic flap of the calf in repair of soft tissue defects of mid-and forefoot.Methods:From September 2015 to Septemler 2020, 15 cases with severe soft tissue defects of mid-and forefoot were repaired with the anterolateral wide pedicled double dynamic flap of the calf. There were 11 males and 4 females with an average age of 37(range, 22-53)years old. Of the 15 cases, the defects were caused by traffic accident in 6 cases and objects smash in 9 cases. Three cases were simple soft tissue defect, and 12 cases combined with fracture or dislocation and bone defect. The size of soft tissue defects ranged from 4 cm×5 cm to 7 cm×12 cm. All wounds of donor sites were repaired by skin grafting. All patients entered follow-ups at the outpatient clinic or through WeChat. The appearance of flaps and limb recovery were recorded after surgery.Results:All cases followed-up for 6-24 (mean, 16) months. Two days after surgery, 1 case had flap swelling and cyanosis, which was improved after pedicle suture removal and surface bloodletting. The pedicle of the flap was slightly bloated in 4 cases, and the texture and appearance were good in 11 cases. The ankle function of all cases recovered satisfactorily. The ranges of ankle motion were 15°-20° for dorsiflexion and 30°-40° for plantar flexion. The donor site healed well and all the skin grafts survived.Conclusion:The anterolateral wide pedicled double dynamic flap of the calf is one of the ideal flaps for repairing the soft tissue defects of the mid-and forefoot with reliable blood supply, sufficient venous return, simple operation and no require a vascular anastomosis.

Objective:To observe the effect of hyaluronidase injection into tendon sheath under muscle bone ultrasound guidance in the treatment of tenosynovitis of long head of biceps brachii.Methods:134 patients with tenosynovitis of the long head of biceps brachii treated in SSL Central Hospital of Dongguan from April 2019 to April 2020 were selected as the research objects. All patients were randomly divided into ordinary injection group and ultrasound-assisted injection group, 67 cases in each group. The general injection group was treated with intra-articular injection of hyaluronidase, and the ultrasound-assisted injection group was treated with intra-tendon sheath injection of hyaluronidase under the guidance of muscle and bone ultrasound. Visual Analog Scales (VAS) score, active flexion joint motion (AFROM), shoulder range of motion (ROM), functional score, flexion strength score, nuclear magnetic resonance imaging (MRI) and local tenosynovitis of the long head of biceps brachii (TLHBB)were measured to evaluate the clinical effect and postoperative complications after treatment.Results:There was no significant difference in gender, age, course of disease, periarthritis of shoulder and disuse atrophy of muscles around shoulder between ordinary injection group and ultrasound-assisted injection group ( P>0.05). After treatment, the AFROM, ROM, function score, forward flexion strength score, and middle wedge angle (MWA) of the two groups were significantly higher than those before treatment ( P<0.05), while the VAS score, humeral head diameter (HHD), biceps long head tendon diameter (BTD), and TLBBB were significantly lower than those before treatment ( P<0.05). The AFROM, ROM, function score, and forward flexion strength score, MWA of the ultrasound-assisted injection group were significantly higher than those of the ordinary injection group ( P<0.05), and the VAS score, HHD, BTD, and TLHBB were significantly lower than those of the ordinary injection group ( P<0.05). The total effective rate of the ultrasound-assisted injection group was higher than that of the ordinary injection group (97.01% vs 85.07%, P<0.05). Conclusions:Intra-tendon sheath hyaluronidase injection guided by ultrasound can effectively treat tenosynouitis of the long head of biceps brachii, relieve shoulder pain and improve shoulder motion.