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 possibility of using a inferior gluteal artery perforator flap (IGAPF) for breast reconstruction in the patient who did not have suitable donor site in back and abdomen.Methods:In November 2024, a 25-year-old unmarried and childless woman with right breast cancer received immediate right breast reconstruction by a right free IGAPF after modified right mastectomy in the Department of Breast and Thyroid Surgery, Second Affiliated Hospital of Hainan Medical University. The locations of perforators were confirmed by both Multi-detector computed tomography angiography (MDCTA) and portable Doppler blood flow detector before surgery. The IGAPF was designed to take the inferior gluteal wrinkle as the lower edge, the axis of the flap was parallel to the inferior gluteal wrinkle, and the width of the flap was estimated where the incision could be directly closed. The size of right IGAPF was 6.0 cm×19.0 cm. Sharp dissection was performed between the sarcolemma and muscle fibres of gluteus, then the perforators were dissected along the direction of muscle fibres of gluteus. The vascular pedicle was kept at about 8.0 cm in length. The diameter of artery was about 2.0 mm and that for the veins was about 1.5 mm. End-to-end anastomoses with the right thoracodorsal artery and vein were successfully carried out. The donor site was directly closed, and it was hidden in the inferior gluteal wrinkle. Postoperative outpatient clinical review was made.Results:Pathological examination reported: an invasive carcinoma of right breast, axillary lymph node metastasis (2/10). The patient recovered well and the flap survived without any complication, i.e. ischemic necrosis, infection and haematoma. The patient was off-bed at 3 days and discharged at 13 days after surgery. At the 40 days of postoperative follow-up, the patient achieved a good recovery and the lower limb activity was not affected by the surgery. The patient was satisfied with the reconstructed breast and donor site recovery. The patient followed with scheduled chemotherapy and subsequent radiotherapy. The volume of reconstructed breast was smaller than the other breast, of which the patient was fully informed before the surgery.Conclusion:A free IGAPF provides an alternative donor sites for achieving a breast reconstruction due to the reliable pedicle vessels and invisible donor scars.

Objective:To explore the possibility of using a inferior gluteal artery perforator flap (IGAPF) for breast reconstruction in the patient who did not have suitable donor site in back and abdomen.Methods:In November 2024, a 25-year-old unmarried and childless woman with right breast cancer received immediate right breast reconstruction by a right free IGAPF after modified right mastectomy in the Department of Breast and Thyroid Surgery, Second Affiliated Hospital of Hainan Medical University. The locations of perforators were confirmed by both Multi-detector computed tomography angiography (MDCTA) and portable Doppler blood flow detector before surgery. The IGAPF was designed to take the inferior gluteal wrinkle as the lower edge, the axis of the flap was parallel to the inferior gluteal wrinkle, and the width of the flap was estimated where the incision could be directly closed. The size of right IGAPF was 6.0 cm×19.0 cm. Sharp dissection was performed between the sarcolemma and muscle fibres of gluteus, then the perforators were dissected along the direction of muscle fibres of gluteus. The vascular pedicle was kept at about 8.0 cm in length. The diameter of artery was about 2.0 mm and that for the veins was about 1.5 mm. End-to-end anastomoses with the right thoracodorsal artery and vein were successfully carried out. The donor site was directly closed, and it was hidden in the inferior gluteal wrinkle. Postoperative outpatient clinical review was made.Results:Pathological examination reported: an invasive carcinoma of right breast, axillary lymph node metastasis (2/10). The patient recovered well and the flap survived without any complication, i.e. ischemic necrosis, infection and haematoma. The patient was off-bed at 3 days and discharged at 13 days after surgery. At the 40 days of postoperative follow-up, the patient achieved a good recovery and the lower limb activity was not affected by the surgery. The patient was satisfied with the reconstructed breast and donor site recovery. The patient followed with scheduled chemotherapy and subsequent radiotherapy. The volume of reconstructed breast was smaller than the other breast, of which the patient was fully informed before the surgery.Conclusion:A free IGAPF provides an alternative donor sites for achieving a breast reconstruction due to the reliable pedicle vessels and invisible donor scars.

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.

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.

Background:alpha-fetoprotein-producing gastric cancer(AFPGC)is relatively rare and special type of gastric cancer,and its clinical symptoms are lack specificity.Aims:To summarize the clinical characteristics and prognosis of AFPGC.Methods:The data of patients with AFPGC from July 2017 to June 2023 at Shaanxi Provincial People's Hospital were retrospectively analyzed,including clinical manifestations,laboratory and examination results,endoscopic results,pathology and treatment.Results:In 17 patients with AFPGC,14 were male and 3 were female.The clinical manifestations were mainly abdominal pain,hematochezia,upper abdominal discomfort,fatigue,etc.AFP was 200-2000 ng/mL.The laboratory examination tests showed that anemia in 16 patients,elevated CEA in 1 patient,abnormal liver function in 2 patients,Hepatitis B Virus-positive in 1 patient,CT showed liver metastasis in 11 patients,lymph node metastasis in 12 patients,cirrhosis in 1 patient.Conclusions:For patients with gastric cancer indicated by examination,if AFP is elevated,AFPGC should be considered.Early detection and surgical treatment can improve the prognosis of AFPGC.

Background:alpha-fetoprotein-producing gastric cancer(AFPGC)is relatively rare and special type of gastric cancer,and its clinical symptoms are lack specificity.Aims:To summarize the clinical characteristics and prognosis of AFPGC.Methods:The data of patients with AFPGC from July 2017 to June 2023 at Shaanxi Provincial People's Hospital were retrospectively analyzed,including clinical manifestations,laboratory and examination results,endoscopic results,pathology and treatment.Results:In 17 patients with AFPGC,14 were male and 3 were female.The clinical manifestations were mainly abdominal pain,hematochezia,upper abdominal discomfort,fatigue,etc.AFP was 200-2000 ng/mL.The laboratory examination tests showed that anemia in 16 patients,elevated CEA in 1 patient,abnormal liver function in 2 patients,Hepatitis B Virus-positive in 1 patient,CT showed liver metastasis in 11 patients,lymph node metastasis in 12 patients,cirrhosis in 1 patient.Conclusions:For patients with gastric cancer indicated by examination,if AFP is elevated,AFPGC should be considered.Early detection and surgical treatment can improve the prognosis of AFPGC.

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 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.

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