[Objective] To compare the characteristics of platelet-rich plasma derived exosomes (PRP-Exos) under different activation conditions and their differential effects on the proliferation capacit of human microvascular endothelial cells (HMEC-1) and human skin fibroblasts (BJ). [Methods] Ten healthy volunteers were recruited, and 10 mL of venous blood anticoagulated with EDTA-K2 was collected. PRP-Exos were prepared and extracted by the secondary centrifugation method. Transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting (WB) detection techniques were used to compare the morphological characteristics, particle size distribution, concentration, and the expression of surface marker proteins of PRP-Exos. Through in vitro cell culture, the differences in morphological changes and proliferation abilities of HMEC-1 and BJ cells induced by PRP-Exos in different activator groups were compared. [Results] 1) TEM observation showed that the morphologies of PRP-Exos in different activator groups were different. 2) NTA analysis showed that compared with the particle size of (109.60±2.71) nm in the normal saline group, the particle sizes of the thrombin group [(104.93±1.55) nm] and the mixed agent group [(103.83±1.58) nm] were relatively smaller, while the particle size of the calcium gluconate group [(113.57±4.70) nm] was larger and its particle size distribution range was wider. There were statistically significant differences among different groups (F=7.019, P<0.05). The concentration of exosomes obtained in the group with the mixture of calcium gluconate and thrombin was the highest [(4.87±0.63)×10⁶ particles/mL, P<0.001]. Both the thrombin group [(2.75±0.13)×10⁶ particles/mL, P < 0.01] and the calcium gluconate group [(3.82±0.06)×10⁶ particles/mL, P<0.001] obtained higher concentrations of exosomes compared with the normal saline group. The concentration in the calcium gluconate group was slightly higher than that in the thrombin group, and there was a significant difference between the two groups (P<0.05). 3) WB analysis showed that CD41, CD81, and TSG101 were expressed on the surface of PRP-Exos, and the protein signal intensities of CD41 and TSG101 in the group with the mixture of thrombin and calcium gluconate were the strongest (P<0.001). 4) The results of in vitro cell culture showed that PRP-Exos in the group with the mixture of thrombin and calcium gluconate could significantly promote the proliferation of HMEC-1 and BJ cells (P<0.05). [Conclusion] The PRP treated with the thrombin and calcium gluconate mixture group yielded the highest concentration of exosomes; under in vitro culture conditions, PRP-Exos from this group significantly promoted the proliferation of HMEC-1 and BJ cells.

Objective To compare the accuracy of maxillary dentition defect models obtained by digital impression and traditional pressure impression,analyzing the influencing factors.Methods Twenty patients with maxillary dentition defects(25 free ends and 18 non-free ends)were selected.Digital impression and traditional pressure impression were utilized to fabricate models of maxillary denti-tion defects.Digital impressions were obtained through intraoral scanning(TRIOS2,3Shape).For the same patient,traditional pressure impression and perfusion plaster model were used for window scanning(SHINING 3D),and the resulting STL format digital model was exported.In Geomagic Control X software,conversion fit and best fit analyses were conducted on the two digital models using the remai-ning abutment as reference landmarks.The total deviation(T)between the two digital models was measured,and positional deviations of the alveolar crest in mesial(M),central(C),distal(D),and maxillary palate(P)regions of the defect area were calculated.A com-parison was made between free end defect area and non-free end defect area,followed by statistical analysis using t-test.Results When the remaining abutments were utilized as reference points for conversion fitting,the total deviation between the two digital models was measured at 0.03 mm,while the positional deviations of M,C,D,P positions amounted to 0.47 mm,0.65 mm,1.48 mm and 0.07 mm respectively.In the best fitting,the total deviation between the two digital models was 0.03 mm,while the positional devia-tions of M,C,D,P,were measured to be 0.50 mm,0.66 mm,1.43 mm and 0.08 mm respectively.The two fitting methods exhibited no statistically significant distinction(P＞0.05).The comparison results between the free end defect area and the non-free end defect ar-ea revealed that the mean deviations of C and D sites in the free end defect area were 1.07 mm and 2.38 mm,respectively,which ex-ceeded those observed in the non-free end defect area(0.08 mm and 0.11 mm,P＜0.05)with statistically significant difference.Conclusion The digital impression for maxillary dentition defect model exhibits a greater deviation compared to the traditional pressure impression model,particularly in the central and distal regions of the free end defect area.

Objective:To compare the efficacy of 3D-printed guide plate assisted versus freehand placement of cannulated screws for the treatment of Sanders type II and III calcaneal fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 29 patients with Sanders type II and III calcaneal fractures admitted to Chonggang General Hospital from June 2020 to October 2022. Among them, there were 18 males and 11 females, with an age range of 22-69 years [(40.1±11.5)years]. Nineteen patients were treated with individualized 3D-printed guide plate assisted placement of cannulated screws (3D-printed group) and 10 were treated with freehand placement of cannulated screws (freehand group). The surgical time, fluoroscopy times, postoperative 6-month calcaneal morphology (length, width, height, B?hler angle and Gissane angle), and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Maryland functional score assessed at 3, 6 months after operation and at the final follow-up were compared between the two groups. The incision healing and complications were observed.Results:The patients were followed up for 6-24 months [(11.3±2.5)months]. The surgical time and fluoroscopy times in the 3D-printed group were (53.4±9.1)minutes and (7.3±1.1)times, respectively, which were shorter than (90.2±16.0)minutes and (16.0±3.2)times in the freehand group (all P<0.01). At 6 months after operation, there was no significant difference in calcaneal length between the two groups ( P>0.05); the calcaneal width, height, B?hler angle and Gissane angle in the 3D-printed group [(34.0±1.8)mm, (47.2±1.6)mm, (27.8±1.0)°, (129.2±2.8)°] were superior than those in the freehand group [(37.5±2.0)mm, (43.0±2.7)mm, (25.8±1.5)°, (125.9±2.5)°] (all P<0.01). At 3, 6 months after operation and at the final follow-up, the values of AOFAS ankle-hindfoot score in the 3D-printed group [(72.2±2.3)points, (79.7±2.3)points, (86.5±4.4)points] were higher than those in the freehand group [(64.2±6.9)points, (73.4±4.2)points, (81.8±3.1)points] (all P<0.05); the values of Maryland score in the 3D-printed group [(71.4±7.7)points, (84.7±2.6)points, (91.5±2.5)points] were higher than those in the freehand group [(65.2±5.6)points, (79.1±3.8)points, (87.1±2.9)points] (all P<0.05). All surgical incisions were healed in stage I. In the 3D-printed group, there were no complications regarding infection, iatrogenic vascular or nerve injury, or fixation failure after surgery. In the freehand group, one patient with lateral sural cutaneous nerve injury was resolved spontaneously without specific treatment. Conclusion:Compared with freehand placement of cannulated screws, 3D-printed guide plate assisted placement of percutaneous placement has the advantages of shorter surgical time, fewer fluoroscopy times, lower reduction loss, better ankle joint function recovery, and less complications in treating Sanders type II and III calcaneal fractures.

【Objective】 To share the experience of autologous platelet-rich plasma(PRP) combined therapy in successful treatment of refractory osteomyelitis with fractures in children. 【Methods】 One case of refractory osteomyelitis with fracture in children failed to respond to traditional treatment for more than 14 months. A total of 20 mL of whole blood was collected from the child, and 6 mL of PRP with 4 to 5 times concentration was prepared by secondary centrifugation. To prepare 2 cm×2 cm platelet concentrate gel (PG), 3 mL of PRP was mixed with a 0.3 mL activator which was then covered with an absorbable dressing. A three-way tube sprayed the remaining 3 mL of PRP and 0.3 mL activator into the surrounding tissues. 【Results】 The X-ray film of the patient followed up for 1 week showed that the fracture line was blurred, and the fracture end had obvious callus formation. The X-ray film reexamination at 4 months showed that the fracture end healed well, the fracture surface healed, and the osteomyelitis healed. 【Conclusion】 Autologous PRP has a good effect in the treatment of refractory osteomyelitis combined with fracture in children, which can provide a new method for clinical treatment.

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.

Objective:To summarize the clinical phenotype of patients with developmental and epileptic encephalopathy 85 caused by SMC1A gene truncating variation.Methods:The clinical data of 4 patients with epileptic encephalopathy caused by SMC1A gene truncating variation from August 2016 to June 2020 were analyzed retrospectively. Related literatures up to October 2021 with the key words "SMC1A" "Developmental and epileptic encephalopathy 85" "SMC1A, epilepsy" and "SMC1A, truncating" in PubMed, CNKI, and Wanfang databases were searched. Relevant literature was summarized and reviewed.Results:These 4 patients were all female. The onset age of seizure were all in the infantile period. They were admitted to the hospital at 3, 2, 11 and 18 months respectively. Focal seizures occurred in all 4 patients, while 1 of them experienced infantile spasm. The characteristic of cluster was observed in all of them with an interval of 14 days to 5.0 months. The seizures were all refractory to different kinds of anti-seizure medications. All 4 patients had severe developmental retardation with microcephaly (head circumference<-2 s). The interictal electroencephalogram (EEG) was characterized by diffuse slow wave. The 4 SMC1A gene variants were p.Gly655fs, p.Glu811fs, p.Arg412fs and p.Ile143fs, all of which were de novo frameshift variation after parental validation. There were another 17 cases with SMC1A gene truncating variation reported in 6 English articles and 1 Chinese article. Among these 21 patients, who were all female, the onset of seizures occurred between 0.5 and 18.0 months of age. Seventeen cases (81%) had the characteristics of cluster attacks, and the intervals of attack cycles were different. Seizure types included generalized tonic-clonic seizure (12 cases (57%)), focal seizure (11 cases(52%)), myoclonic(4 cases(19%)), spasm (4 cases(19%)), atypical absence (3 cases(14%)), tonic seizure (2 cases (10%)), and atonia (1 case(5%)). In addition, 4 cases (19%) had status epilepsy. All patients had moderate to severe mental retardation. Microcephaly was found in all patients. Among 18 cases,EEG in 8 cases had diffuse slow wave background. Brain magnetic resonance imaging (MRI) was normal in 13 cases (62%). Other MRI changes included cerebellar atrophy (3 cases), thin corpus callosum (3 cases), and lateral ventricular enlargement (2 cases). Twenty patients did not respond well to antiepileptic drugs. Conclusions:The clinical phenotypes of patients with epilepsy encephalopathy 85 caused by SMC1A gene truncating variation are characterized by female, early-onset, clustering of seizures, development delay and microcephaly. Diffuse slow waves are shown in interictal EEG in partial. Response to treatment and prognosis are poor.

Objective:To summarize the clinical characteristics of children with interleukin-1 receptor associated kinase 4 (IRAK4) deficiency.Methods:The clinical data of a child with IRAK4 deficiency who was admitted to the Department of Neurology of Shenzhen Children′s Hospital for several times from June 2019 to August 2020 were retrospectively analyzed. Related literature up to January 2021 with the key words "IRAK4 gene variation", and "interleukin-1 receptor-associated kinase 4 deficiency" in PubMed, CNKI, Wanfang, and CQVIP databases were searched. The clinical characteristics of this disease were summarized and analyzed.Results:The boy was 6 years of age and had recurrent respiratory tract infections. He was improved after antibiotic treatment. His clinical manifestation included Streptococcus pneumoniae meningoencephalitis, multiple sclerosis, invasive discitis and inflammatory bone destruction. Family-based whole exome sequencing showed that the boy had a homozygous frameshift variation in the IRAK4 gene, NM_016123.3:C.540del (p.Phe180leufs*26), and both parents were heterozygous. A total of 23 cases were reported in ten English articles. Together with this case, there were 24 cases, including 13 males and 11 females. The age of onset was 8 days to 7 years. The main manifestations were recurrent invasive bacterial infection, including 11 cases with Streptococcus pneumoniae meningitis, 9 cases with Streptococcus pneumoniae and (or) Staphylococcus aureus septicemia, 1 case with Pseudomonas aeruginosa meningitis, 1 case of salmonella infection, and 1 case with Staphylococcus aureus skin abscess. Only 1 case had recurrent virus infection. There were 2 patients with autoimmune diseases, 1 with autoimmune encephalitis and the other one with juvenile idiopathic arthritis. Among the 24 cases, 10 died (9 in infancy). Most of the surviving children were diagnosed early and received antibiotics preventively and intravenous immunoglobulin (IVIG). Their susceptibility to infection decreased year by year, and could be close to normal children at the age of 14 years. Among the 24 cases, 21 cases had homozygous variation of IRAK4 gene and 3 cases had complex heterozygous variation. There were 15 kinds of variation, including 9 kinds of frameshift variation, 4 kinds of nonsense variation and 2 kinds of missense variation. One candidate variation hotspot was c.877 c>T (3 cases). Conclusions:IRAK4 deficiency mainly manifest as recurrent and invasive bacterial infection, with Streptococcus pneumoniae meningitis or septicemia being the most common. A few patients are complicated with autoimmune diseases. The mortality rate is high in infancy, early diagnosis and treatment can avoid severe illness or death.

Objective:To investigate the safety and efficacy of venetoclax with low-dose cytarabine (LDAC) in Chinese patients with acute myeloid leukemia (AML) who are unable to tolerate intensive induction chemotherapy.Methods:Adults ≥ 18 years with newly diagnosed AML who were ineligible for intensive chemotherapy were enrolled in this international, randomized, double-blind, placebo-controlled trial. Globally, patients ( n=211) were randomized 2∶1 to either venetoclax with LDAC or placebo with LDAC in 28-d cycles, with LDAC on days 1-10. The primary endpoint was OS; the secondary endpoints included response rates, event-free survival, and adverse events. Results:A total of 15 Chinese patients were enrolled (venetoclax arm, n=9; placebo arm, n=6) . The median age was 72 years (range, 61-86) . For the primary analysis, the venetoclax arm provided a 38% reduction in death risk compared with the placebo[hazard ratio ( HR) , 0.62 (95% CI 0.12-3.07) ]. An unplanned analysis with an additional 6 months of follow-up demonstrated a median OS of 9.0 months for venetoclax compared with 4.1 months for placebo. The complete remission (CR) rates with CR with incomplete blood count recovery (CRi) were 3/9 (33%) and 0/6 (0%) , respectively. The most common non-hematologic adverse effects (venetoclax vs placebo) were hypokalemia[5/9 (56%) vs 4/6 (67%) ], vomiting[4/9 (44%) vs 3/6 (50%) ], constipation[2/9 (22%) vs 4/6 (67%) ], and hypoalbuminemia[1/9 (11%) vs 4/6 (67%) ]. Conclusion:Venetoclax with LDAC demonstrated meaningful efficacy and a manageable safety profile in Chinese patients consistent with the observations from the global VIALE-C population, making it an important treatment option for patients with newly diagnosed AML who are otherwise ineligible for intensive chemotherapy.