Cells and exosomes derived from them are extensively used as biological carrier systems. Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins, while exosomes, due to their small size, cross barriers and penetrate tumors efficiently. However, challenges remain, cells' large size restricts tissue penetration, and exosomes have limited targeting accuracy and short circulation times. To address these challenges, we developed a novel concept termed exosomal spheres. This approach involved incorporating platelet-derived exosomes shielded with phosphatidylserine (PS) and linked via pH-sensitive bonds for drug delivery applications. The study demonstrated that, compared with exosomes, the exosomal spheres improved blood circulation through the upregulation of CD47 expression and shielding of phosphatidylserine, thereby minimizing immune clearance. Moreover, the increased expression of P-selectin promoted adhesion to circulating tumor cells, thereby enhancing targeting efficiency. Upon reaching the tumor site, the hydrazone bonds of exosome spheres were protonated in the acidic tumor microenvironment, leading to disintegration into uniform-sized exosomes capable of deeper tumor penetration compared to platelets. These findings suggested that exosome spheres addressed the challenges and offered significant potential for efficient and precise drug delivery.

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

Objective To evaluate the effect of red-blue light photon assisted therapy on wound healing after flap reconstruction of limb traumatic defects.Methods A total of 146 patients who were admitted to the Ward of Microsurgery of ⅢA hospital of Shanghai from January 2020 to December 2021 and received flap reconstruction surgery for soft tissue defects of limbs were included in this prospective observational study.According to the order of admission,patients were divided into a control group(n=70)and an trial group(n=76).In the control group,a 60W thermal lamp was offered to the patients for locally heating the flaps,with continuous irradiation for 24 hours with a maintaining power of 1-2W,at an approximately 30-45 cm in distance from the flap.In the trial group,based on the thermal irradiation applied to the control group,a combined red and blue light photon irradiation therapy was offered as an additional measure,by twice a day at 20 minutes per session of blue-red light photon irradiation,at 8-12cm in distance from the flap.The two groups were compared in terms of tension of tissues around flap,incidence of infection within 7 days after surgery and the survival of flap within 2 weeks after surgery.Results The two groups showed no significant difference in terms of tissue tension between the 1st and 3rd day after surgery(P<0.05),but with significant differences on the 5th and 7th day after surgery(P>0.05).The trial group exhibited significantly lower incidence of infection within 7 days after surgery compared to that of the control group(P<0.05),and with a significantly higher flap survival rate at 2 weeks after surgery(P<0.05).Conclusion After the flap reconstruction of soft tissue defects of limbs,a red-blue light assisted photon irradiation therapy can effectively improve postoperative tissue tension around a flap,reduce infection rate and improve the survival rate of a flap.It provides an effective and safe interventional measures for postoperative care of the transferred flap.

Objective:To evaluate the residual risk (RR) of transfusion transmitted HIV (TT-HIV) after the implementation of nucleic acid amplification test (NAT) in blood screening test among blood centers in China.Methods:The data of blood donors and HIV infection markers from 2017 to 2020 were collected from 28 blood centers via the Platform of Comparison of blood establishments Practice in Chinese Mainland. The new infection rate/window period mathematical model was used for two types of blood screening strategies, namely, two rounds ELISA plus individual NAT take turn with pooling NAT (2ELISA+ ID-NAT/MP-NAT) and two ELISA plus one round pooling NAT (2ELISA+ MP-NAT), and the RR of HIV infection was estimated also based on first donors (FDs) and repeated donors (RDs) in different blood donation years. T-test analyses were conducted for comparing TT HIV RR among FDs and RDs in different blood donation years with two blood screening strategies, and the variation trend of RR in HIV test was observed.Results:From 2017 to 2020, the RR of FDs in 2ELISA+ ID-NAT/MP-NAT blood screening strategy was 2.869/10 6 person-year, 3.795/10 6 persons-year, 3.879/10 6 person-year, and 2.890/10 6 person-year respectively. The RR of RDs was 1.797/10 6 person-year, 1.502/10 6 person-year, 1.857/10 6 person-year, and 1.483/10 6 person-year respectively. Significant difference exists between RR of FDs and RDs, with F=9.898 and p<0.05. In 2ELISA+ MP-NAT strategy, the RR of FDs was 3.508/10 6 person-year, 1.868/10 6 person-year, 2.204/10 6 person-year, and 1.765/10 6 person-year respectively. The RR of RDs was 0.948/10 6 person-year, 0.926/10 6 person-year, 0.748/10 6 person-year, and 0.682/10 6 person-year respectively. Statistical difference existed between RR of FDs and RDs, with F=17.126 and P<0.05. There was no significant difference between the RR of FDs in these two strategies with F=3.493 and P>0.05, while there was a difference between the RR of RDs in these two strategies with F=24.516 and P<0.05, and a difference between the RR of total donors (TDs) in these two strategies F=20.216 and P<0.05. Conclusions:The RR of TT HIV significantly decreased after the introduction of NAT into blood test among blood centers in China. There were some differences in the RR of HIV testing among different blood screening strategies. There could be significant differences in the RR of HIV testing among different groups of blood donors. Compared with FDs, RDs is the low risk group for HIV.

Objective:To investigate the value of ultrasonography in diagnosis of transposition of great arteries of the fetus at 11-13 + 6 weeks gestation. Methods:A prospective study was conducted on fetuses screened by ultrasound in the first trimester in Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region between January 2015 and March 2022. Fetal heart structure was screened by three-section screening method. Fetuses with suspected transposition of the great arteries at 11-13 + 6 weeks gestation underwent followed-up ultrasound examination, chromosome and gene test results. The ultrasound characteristics and prognosis pregnancy outcomes were summarized. Results:Twenty-one cases of transposition of the great arteries were detected by ultrasonography, including complete transposition of great arteries (20 cases) and congenitaly corrected transposition of the great arteries (1 case). Two cases were miss diagnosed. Twenty-one cases showed parallel signs of two major arteries on grayscale outflow section at 11-13 + 6 weeks gestation. There were 6 cases with aneuploid ultrasonographic soft markers abnormality, 2 cases with extracardiac malformation. Chromosome and microarray analysis were performed in 13 cases. 4 cases with chromosomal abnormality. Four cases of chromosomal abnormalities were associated with ultrasonographic soft markers abnormality, and 1 case with extracardiac malformation.In the 23 cases, 20 cases were induced, 1 miscarried, and 2 delivered to term. Among the fetuses delivered at term, 1 case died before neonatal operation and 1 case survived. Conclusions:Standardized ultrasound scan at 11-13 + 6 weeks has high accuracy in diagnosis of transposition of the great arteries. And the incidence of chromosomal abnormality is high with ultrasonographic soft markers abnormality or extracardiac malformation.

Objective To investigate the clinical features, liver histological features, and diagnostic and treatment methods for patients with myeloproliferative neoplasms (MPN) with portal hypertension as the main manifestation. Methods A retrospective analysis was performed for related data of the patients who attended the hospital due to portal hypertension and were finally diagnosed with MPN in Liver Research Center, Beijing Friendship Hospital, from January 2019 to February 2022, including clinical manifestation, liver pathological features, treatment, and follow-up results. Results Nine patients were included in this study, and all the patients had splenomegaly and esophageal and gastric varices, while portal vein thrombosis was observed in eight patients. All patients had normal or slightly abnormal liver function and routine blood test results. Six patients underwent liver biopsy, without the formation of fibrous septum and pseudolobule, and hepatic extramedullary hematopoiesis was observed in two patients. All nine patients underwent bone marrow biopsy and genetic testing, among whom six had essential thrombocythemia and three had primary myelofibrosis, and genetic testing revealed JAK - 2V617F gene mutation in seven patients and CALR gene mutation in two patients. Conclusion MPN is one of the rare causes of portal hypertension and has the clinical manifestations of esophageal and gastric varices, splenomegaly, and even megalosplenia, without the manifestations of hypersplenism such as leukopenia and thrombocytopenia. Detection of the JAK - 2V617F and CALR genes can improve the diagnostic rate of MPN.

Portal hypertension is a serious complication of liver cirrhosis resulting from the increases in portal vascular resistance and portal blood inflow. Both etiological and non-etiological therapies can effectively reduce portal venous pressure to a certain degree, but with an unsatisfactory effect in improving prognosis. New therapeutic drugs targeting the reduction in intrahepatic vascular resistance may help to achieve the reversal of portal hypertension. Based on the pathogenesis of cirrhotic portal hypertension, this article summarizes the current pharmacotherapies from the aspects of etiological and non-etiological therapies, so as to provide a comprehensive theoretical and evidence-based basis for clinical treatment options.

Objective:To investigate the value of atrioventricular valve regurgitation in predicting atrioventricular septal defect (AVSD) in the first trimester.Methods:Fetuses were examined prospectively by ultrasound at 11-13 + 6 weeks in Maternity & Child Healthcare Hospital of Guangxi Zhuang Autonomous Region between February 2016 and February 2021. Congenital heart disease was screened and atrioventricular valve regurgitation was observed in fetuses of gestational age 11 to 13 + 6 weeks using color Doppler in four-chamber view and three vessels and trachea view. Results:Totally 43 549 fetuses of gestational age 11 to 13 + 6 weeks were screened by echocardiography, of whom 37 cases were screened out with AVSD, including complete atrioventricular septal defect (31 cases), partial atrioventricular septal defect(3 cases) and intermediate atrioventricular septal defect(1 cases), 2 cases were misdiagnosed, and ultrasonic scanning in the second trimester found 2 missed cases of intermediate atrioventricular septal defect. Atrioventricular valve regurgitation was observed in 91.89% of atrioventricular septal defects (34/37) in the first trimester, 59.46% (22/37) nuchal translucency greater than 95th percentile, 29.73% (11/37) absence of nasal bone, 32.43% (12/37) ductus venosus A wave inversion, and 40.54% (15/37) had tricuspid regurgitation. The sensitivity of common atrioventricular valve regurgitation in predicting atrioventricular septal defect is better than other ultrasonic indexes. Conclusions:Atrioventricular regurgitation can be used as a clue to predict atrioventricular septal defect in the first trimester, which is beneficial to detect atrioventricular septal defect in the first trimester.

Objective:To assess the value of ultrasonography in the diagnosis of fetal isomerism syndrome in the first trimester.Methods:Sonographic features of 15 fetuses with isomerism syndrome diagnosed in the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from January 2015 to March 2020 were reviewed. Ultrasonic characteristics in the first trimester were analyzed, and the ultrasonic characteristics of early mid-trimester and pathological anatomical results were combined for comparison.Results:There were 6 cases of left isomerism syndrome (LIS) and 9 cases of right isomerism syndrome (RIS) in the 15 fetues.Increased nuchal translucency(NT) (≥3.0 mm, 6 cases), reversed A wave in ductus venosus (10 cases), and atrio-ventricular valve regurgitation (14 cases) were found during the first trimester. There were 14 cases with abnormal visceral laterality. Of the 15 fetues, 14 cases with cardiac malformations, including 6 cases of functional single ventricle, 8 cases of complete atrioventricular septal defect (CAVSD), and 12 cases with great artery abnormalities. All of the 6 LIS cases had bradycardia, 3 cases had interruption of inferior vena cava (IVC). Six cases of RIS had juxtaposition of descending aorta and IVC, and 1 case of RIS had total anomalous pulmonary vein drainage. The major structural malformations were consistent with the early mid-trimester ultrasound examination or autopsy. Karyotype and chromosomal microarray were available in 12 cases and all were normal.Conclusions:Isomerism syndrome has high positive rate of fetal aneuploidies ultrasonographic marker, especially with the atrio-ventricular valve regurgitation, but the risk of chromosome abnormality is low. Ultrasound screening for fetal cardiac structural abnormalities is beneficial to the early diagnosis of isomerism syndrom in the first trimester.

Objective:To explore the feasibility and prognosis of prenatal ultrasonic diagnosis of fetal isolated vascular ring at 11-13 + 6 weeks. Methods:A total of 36 996 fetuses were selected to compare the results of ultrasound screening at 11-13 + 6 weeks and 20-24 weeks of pregnancy in Guangxi Maternity & Child Healthcare Hospital from January 2016 to January 2020, the reasons for missed diagnosis and misdiagnosis of fetal isolated vascular ring by ultrasonography in the first trimester were summarized. Results:Thirty-five cases were diagnosed as isolated vascular ring in the first trimester, including 19 cases right aortic arch combined with aberrant left subclavian artery with "U-shaped" vascular ring, 7 cases double aortic arch with "O-shaped" vascular ring, and 9 cases aberrant right subclavian artery with "C-shaped" vascular ring. While 155 cases were diagnosed as isolated vascular ring at 20-24 weeks of pregnancy, consisting of 18 cases of combined with aberrant left subclavian artery, 9 cases of double aortic arch, 126 cases of aberrant right subclavian artery and 2 cases of pulmonary artery sling, the diagnosis coincidence rates were 94.74%, 77.78%, 7.14%, 0(Kappa value were 0.97, 0.88, 0.13, 0). For the diagnosis of right aortic arch combined with aberrant left subclavian artery, double aortic arch and aberrant right subclavian artery in the first trimester, the specificities were 99.99%, 100%, 100%, the sensitivities were 100%, 77.78%, 7.14%, the false-positive rates were 0.01%, 0, 0, the false-negative rates were 0, 22.22%, 92.86%, and the Youden′s indices were 0.99, 0.78, 0.07.Conclusions:Right aortic arch combined with aberrant left subclavian artery and double aortic arch have high coincidence rate by ultrasonography in the first trimester, while the diagnostic coincidence rate of isolated aberrant right subclavian artery was low. Ultrasound screening for isolated vascular ring in the first trimester still needs ultrasound examination in the second trimester to exclude the minor cardiac malformations that are difficult to diagnose in the first trimester.