Cranial bone defect repair remains a significant challenge in craniomaxillofacial surgery， particularly when defects exceed the critical size defect （CSD） threshold， rendering them incapable of spontaneous healing without external intervention. Mechanical forces—including compression， tension， and shear stress—play a pivotal role in cranial development and regeneration. These forces regulate osteoblast differentiation and bone regeneration by activating key mechanotransduction pathways， such as the Wnt/β-catenin signaling pathway， the piezoelectric mechanosensitive ion channel Piezo1， and the transcriptional co-activators Yes-associated protein （Yes-Associated Protein，YAP） and Transcriptional co-activator with PDZ-binding motif （Transcriptional co-activator with PDZ-binding motif，TAZ）. Distinct types of mechanical forces exert specific effects on cellular behavior and the microenvironment. Clinically， applications such as Negative Pressure Wound Therapy （NPWT） have demonstrated efficacy in promoting angiogenesis-osteogenesis coupling， while tensile forces stimulate the dura mater to secrete osteogenic factors. Preliminary studies using artificial periosteum and other biomaterials have further validated that appropriate mechanical stimulation enhances bone repair. This review summarizes the effects of various mechanical forces and their associated signaling pathways on osteoblasts and their microenvironment， alongside an overview of current technological applications in this field.

Objective:The clinical symptoms of children with global developmental delay (GDD) were analyzed to provide the scientific basis for the intervention of children with GDD.Methods:The results of the neuro-psychobehavioral scale were collected from 32 511 children with GDD from June 2020 to November 2023. Inclusion criteria: Children diagnosed with GDD according to the Diagnostic and Statistical Manual of Mental Disorders-V, ages 0.0 to 4.9 years. Exclusion criteria: children with common hearing impairment and visual impairment. The Chi-square tests were used for statistical analysis.Results:There were more boys than girls with GDD in outpatient clinics (68.2% vs. 31.8%). Among the children, the proportion of developmental delay in 5, 4, 3, and 2 domains was 31.1%, 23.4%, 22.9% and 22.6% respectively. The rate of delay in 2-3 domains was lower in boys (41.9%) than in girls (53.1%). The rate of delay in 4-5 domains was higher in boys (58.1%) than in girls (46.9%) ( χ2=352.11, P<0.001). Overall, outpatient GDD decreased with age. From 1.0-1.9 to 4.0-4.9 years of age, the proportion of children with developmental delay in 5 domains increased with age (18.2%, 36.4%, 43.9%, 52.4%). Among children aged 0.0-0.9 years, the proportion of 2 domains of developmental delay was higher (33.4%).Among children aged 1.0-1.9 years, the proportion of 2-3 domains of developmental delay was higher (30.7%). Among children aged 2.0-, 3.0-, 4.0-4.9 years, the proportion of developmental delay in 5 domains was higher (36.4%, 43.9%, 52.4%). In children with GDD, the fine motor delay occurred most frequently (85.1%), followed by social self-care (83.9%), language (79.0%), adaptation (62.3%), and gross motor (52.8%). The frequency of developmental delays in fine motor, adaptability, language, and social self-care in boys was higher than that in girls ( χ2=161.37, χ2=41.10, χ2=320.90, χ2=238.54, all P<0.001). The age groups with the highest delay incidence of gross motor, fine motor, adaptability, language, and social self-care were: 4.0-4.9 years (70.6%), 3.0-3.9 years (97.4%), 4.0-4.9 years (81.2%), 2.0-2.9 years (90.9%),2.0-2.9 years (95.4%). The proportions of fine motor delay in GDD children aged 0.0-0.9, 3.0-3.9 and 4.0-4.9 years were (74.5%, 97.4%, 96.8%) and the proportions of social self-care delay in GDD children aged 1.0- and 2.0-2.9 years were (92.1%, 95.4%). Peripheral and mild developmental delays were predominant in children with GDD. The proportion of severe language delay (6.4%) was higher than that in other fields. Conclusions:The proportion of GDD children with developmental delay in 4-5 domains was 54.5%. The most frequent domain of delay was fine motor. The frequencies of developmental delays in fine motor skills, adaptability, language, and social self-care in boys were higher than in girls. Most of the developmental delays in GDD children were marginal and mild. The rate of severe developmental delay in language was higher than in other domains.

Objective:The clinical symptoms of children with global developmental delay (GDD) were analyzed to provide the scientific basis for the intervention of children with GDD.Methods:The results of the neuro-psychobehavioral scale were collected from 32 511 children with GDD from June 2020 to November 2023. Inclusion criteria: Children diagnosed with GDD according to the Diagnostic and Statistical Manual of Mental Disorders-V, ages 0.0 to 4.9 years. Exclusion criteria: children with common hearing impairment and visual impairment. The Chi-square tests were used for statistical analysis.Results:There were more boys than girls with GDD in outpatient clinics (68.2% vs. 31.8%). Among the children, the proportion of developmental delay in 5, 4, 3, and 2 domains was 31.1%, 23.4%, 22.9% and 22.6% respectively. The rate of delay in 2-3 domains was lower in boys (41.9%) than in girls (53.1%). The rate of delay in 4-5 domains was higher in boys (58.1%) than in girls (46.9%) ( χ2=352.11, P<0.001). Overall, outpatient GDD decreased with age. From 1.0-1.9 to 4.0-4.9 years of age, the proportion of children with developmental delay in 5 domains increased with age (18.2%, 36.4%, 43.9%, 52.4%). Among children aged 0.0-0.9 years, the proportion of 2 domains of developmental delay was higher (33.4%).Among children aged 1.0-1.9 years, the proportion of 2-3 domains of developmental delay was higher (30.7%). Among children aged 2.0-, 3.0-, 4.0-4.9 years, the proportion of developmental delay in 5 domains was higher (36.4%, 43.9%, 52.4%). In children with GDD, the fine motor delay occurred most frequently (85.1%), followed by social self-care (83.9%), language (79.0%), adaptation (62.3%), and gross motor (52.8%). The frequency of developmental delays in fine motor, adaptability, language, and social self-care in boys was higher than that in girls ( χ2=161.37, χ2=41.10, χ2=320.90, χ2=238.54, all P<0.001). The age groups with the highest delay incidence of gross motor, fine motor, adaptability, language, and social self-care were: 4.0-4.9 years (70.6%), 3.0-3.9 years (97.4%), 4.0-4.9 years (81.2%), 2.0-2.9 years (90.9%),2.0-2.9 years (95.4%). The proportions of fine motor delay in GDD children aged 0.0-0.9, 3.0-3.9 and 4.0-4.9 years were (74.5%, 97.4%, 96.8%) and the proportions of social self-care delay in GDD children aged 1.0- and 2.0-2.9 years were (92.1%, 95.4%). Peripheral and mild developmental delays were predominant in children with GDD. The proportion of severe language delay (6.4%) was higher than that in other fields. Conclusions:The proportion of GDD children with developmental delay in 4-5 domains was 54.5%. The most frequent domain of delay was fine motor. The frequencies of developmental delays in fine motor skills, adaptability, language, and social self-care in boys were higher than in girls. Most of the developmental delays in GDD children were marginal and mild. The rate of severe developmental delay in language was higher than in other domains.

Objective:To evaluate the efficacy and safety of high-dose injectable dexlansoprazole in the treatment of acute upper gastrointestinal ulcer hemorrhage.Methods:This study was a randomized, double-blind, positive drug parallel controlled, multicenter clinical trial led by the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital), with participation from 43 hospitals such as Yichun People′s Hospital, Army Medical Center of PLA (Chongqing Daping Hospital), etc. From August 31, 2019 to May 25, 2020, 346 patients with upper gastrointestinal hemorrhage caused by acute gastric and (or) duodenal ulcer were selected. The subjects were randomly divided into experimental group and control group according to a 2 to 1 stratification scheme using the SAS 9.4 software. The medication regimen for the experimental group was intravenous injection of dexlansoprazole 30 mg/times, once every 12 h, while the medication regimen for the control group was intravenous injection of lansoprazole and dexlansoprazole mimetics, 30 mg/times, once every 12 h; the treatment course was 5 days. The primary efficacy indicator (72 h effective hemostasis rate), the secondary efficacy indicator(clinical hemostasis rate at 24, 48, and 120 h, and the proportion of subjects who underwent endoscopic treatment or surgical procedures again due to hemorrhage within 5 days), and the incidence of adverse reactions were compared between the 2 groups. Binomial distribution normal approximation method was performed to calculate the 95% confidence interval (95% CI) of the difference in hemostasis rate between the experimental group and the control group. Fisher′s exact test was used for statistical analysis. Results:A total of 329 patients (219 cases in the experimental group and 110 cases in the control group) were enrolled. The 72 h effective hemostasis rate (95% CI) of the experimental and control group was 95.9%(210/219, 92.3% to 98.1%) and 93.6%(103/110, 87.3% to 97.4%), respectively, and the difference was not statistically significant ( P>0.05). The difference in the 72-hour effective hemostasis rate(95% CI) between the experimental and the control group was 2.3% (-3.0% to 7.5%). The clinical hemostasis rates at 24, 48, and 120 h of the treatment were 82.2% (176/214), 99.1%(210/212), and 100.0%(210/210) in the experimental group, and 85.2%(92/108), 98.1%(104/106), and 100.0%(105/105) in the control group, respectively, and the differences were not statistically significant (all P>0.05). The proportion of subjects who underwent endoscopic treatment and surgical procedure again within 5 days (95% CI)of the experimental group and control group was 0 (0 to 1.7%) and 1.9% (0.2% to 6.5%), respectively, and the difference was not statistically significant ( P>0.05). The result of safety evaluation showed that the overall incidence of adverse reactions of the experimental group and the control group was 6.4% (14/219) and 11.8% (13/110), respectively, and the difference was not statistically significant ( P>0.05). Conclusion:High dose injectable dexlansoloprazole is an effective and safe treatment for upper gastrointestinal ulcer hemorrhage, and suitable for clinical application.

BACKGROUND:Ankylosing spondylitis is a chronic inflammatory disease with chronic rheumatic immunity.Soft tissue ossification and fusion and spinal stiffness can cause biomechanical changes. OBJECTIVE:To reconstruct the lumbar-sacral intervertebral disc in ankylosing spondylitis patients with lumbar kyphosis by finite element analysis,and to study the range of motion of each segment of T11-S1 and the biomechanical characteristics of annulus fibrosus and nucleus pulposus. METHODS:The imaging data were obtained from an ankylosing spondylitis patient with lumbar kyphosis.The original CT image data of continuously scanned spine were imported into Mimics 21.0 in DICOM format,and T11-S1 was reconstructed respectively.The established model was imported into 3-Matic software in the format of"Stl"to reconstruct the intervertebral disc,and the fibrous intervertebral disc model was obtained.The improved model was further imported into Hypermesh software,and the vertebra,nucleus pulposus,annulus fibrosus and ligament were mesh-divided.After the material properties were given,the model was imported into ABAQUS software to observe the range of motion of each vertebral body in seven different working conditions of T11-S1,and analyze the biomechanical characteristics of each segment of annulus fibrosus and nucleus pulposus. RESULTS AND CONCLUSION:(1)The range of motion of L1 vertebrae was higher than that of other vertebrae under six different working conditions:extension,forward flexion,rotation(left and right),and lateral flexion(left and right).The maximum range of motion was 2.18° during L1 vertebral flexion,and the minimum range of motion was 0.12° during L5 vertebral extension.(2)The annular fiber flexion at L2-L3 segments was greater than the extension(P<0.05),and the annular fiber flexion at L3-L4 and L4-L5 segments was less than the extension(P<0.05).The left rotation of L1-L2 annular fibers was greater than the right rotation(P<0.05).The left flexion of the annulus was greater than the right flexion in L1-L2,L2-L3,L3-L4,L4-L5 and L5-S1 segments(P<0.05).(3)The nucleus pulposus stresses of T11-L12,L1-L2,L2-L3,L3-L4 and L4-L5 segments in forward flexion were greater than in extension(P<0.05).The left rotation of T12-L1 and L3-L4 segments was smaller than the right rotation(P<0.05),and that of T11-T12,L1-L2,and L2-L3 segments was larger than the right rotation(P<0.05).The left flexion was larger than the right flexion in the T11-S1 segment.(4)It is concluded that in ankylosing spondylitis patients with lumbar kyphosis,the minimum range of motion of the vertebral body is located at the L5 vertebral body in extension.To prevent fractures,it is recommended to avoid exercise in the extension position.During the onset of lumbar kyphosis in patients with ankylosing spondylitis,the maximum stress of the annulus fibrosus and nucleus pulposus is located in the L1-L2 segment,which is fixed and will not alter with the change of body position.The late surgical treatment and correction of deformity should focus on releasing the pressure of the annulus fibrosus and nucleus pulposus in this segment to avoid the rupture of the annulus fibrosus and the injury of the nucleus pulposus.

Objective:To evaluate the efficacy and safety of high-dose injectable dexlansoprazole in the treatment of acute upper gastrointestinal ulcer hemorrhage.Methods:This study was a randomized, double-blind, positive drug parallel controlled, multicenter clinical trial led by the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital), with participation from 43 hospitals such as Yichun People′s Hospital, Army Medical Center of PLA (Chongqing Daping Hospital), etc. From August 31, 2019 to May 25, 2020, 346 patients with upper gastrointestinal hemorrhage caused by acute gastric and (or) duodenal ulcer were selected. The subjects were randomly divided into experimental group and control group according to a 2 to 1 stratification scheme using the SAS 9.4 software. The medication regimen for the experimental group was intravenous injection of dexlansoprazole 30 mg/times, once every 12 h, while the medication regimen for the control group was intravenous injection of lansoprazole and dexlansoprazole mimetics, 30 mg/times, once every 12 h; the treatment course was 5 days. The primary efficacy indicator (72 h effective hemostasis rate), the secondary efficacy indicator(clinical hemostasis rate at 24, 48, and 120 h, and the proportion of subjects who underwent endoscopic treatment or surgical procedures again due to hemorrhage within 5 days), and the incidence of adverse reactions were compared between the 2 groups. Binomial distribution normal approximation method was performed to calculate the 95% confidence interval (95% CI) of the difference in hemostasis rate between the experimental group and the control group. Fisher′s exact test was used for statistical analysis. Results:A total of 329 patients (219 cases in the experimental group and 110 cases in the control group) were enrolled. The 72 h effective hemostasis rate (95% CI) of the experimental and control group was 95.9%(210/219, 92.3% to 98.1%) and 93.6%(103/110, 87.3% to 97.4%), respectively, and the difference was not statistically significant ( P>0.05). The difference in the 72-hour effective hemostasis rate(95% CI) between the experimental and the control group was 2.3% (-3.0% to 7.5%). The clinical hemostasis rates at 24, 48, and 120 h of the treatment were 82.2% (176/214), 99.1%(210/212), and 100.0%(210/210) in the experimental group, and 85.2%(92/108), 98.1%(104/106), and 100.0%(105/105) in the control group, respectively, and the differences were not statistically significant (all P>0.05). The proportion of subjects who underwent endoscopic treatment and surgical procedure again within 5 days (95% CI)of the experimental group and control group was 0 (0 to 1.7%) and 1.9% (0.2% to 6.5%), respectively, and the difference was not statistically significant ( P>0.05). The result of safety evaluation showed that the overall incidence of adverse reactions of the experimental group and the control group was 6.4% (14/219) and 11.8% (13/110), respectively, and the difference was not statistically significant ( P>0.05). Conclusion:High dose injectable dexlansoloprazole is an effective and safe treatment for upper gastrointestinal ulcer hemorrhage, and suitable for clinical application.

Astragalosides are the main active constituents of traditional Chinese medicine Huang-Qi, of which cycloastragenol-type glycosides are the most typical and major bioactive compounds. This kind of compounds exhibit various biological functions including cardiovascular protective, neuroprotective, etc. Owing to the limitations of natural sources and the difficulties encountered in chemical synthesis, re-engineering of biosynthetic machinery will offer an alternative and promising approach to producing astragalosides. However, the biosynthetic pathway for astragalosides remains elusive due to their complex structures and numerous reaction types and steps. Herein, guided by transcriptome and phylogenetic analyses, a cycloartenol synthase and four glycosyltransferases catalyzing the committed steps in the biosynthesis of such bioactive astragalosides were functionally characterized from Astragalus membranaceus. AmCAS1, the first reported cycloartenol synthase from Astragalus genus, is capable of catalyzing the formation of cycloartenol; AmUGT15, AmUGT14, AmUGT13, and AmUGT7 are four glycosyltransferases biochemically characterized to catalyze 3-O-xylosylation, 3-O-glucosylation, 25-O-glucosylation/O-xylosylation and 2'-O-glucosylation of cycloastragenol glycosides, respectively. These findings not only clarified the crucial enzymes for the biosynthesis and the molecular basis for the structural diversity of astragalosides in Astragalus plants, also paved the way for further completely deciphering the biosynthetic pathway and constructing an artificial pathway for their efficient production.

Objective::The size and morphology of the right ventricular outflow tract (RVOT) in patients suffering from long-term pulmonary regurgitation (PR) after native RVOT (NRVOT) reconstruction are important factors affecting the feasibility, safety, and effectiveness of transcatheter pulmonary valve replacement. The purpose of this study was to evaluate the feasibility, safety, and effectiveness of a transthoracic Salus valve (Balance Medical Technology Co., Ltd, Beijing, China) in patients with moderate-to-severe PR after NRVOT reconstruction.Methods::Patients with moderate-to-severe PR after NRVOT reconstruction were selected between June 2021 and November 2021 at Beijing Anzhen Hospital. Demographic data as well as preoperative, intraoperative, and follow-up data were reviewed.Results::Ten patients with moderate-to-severe PR after NRVOT reconstruction underwent physical examination, transthoracic echocardiography, and cardiovascular magnetic resonance imaging. Seven patients were selected for transthoracic Salus valve replacement. Six patients underwent implantation of the Salus valve successfully. One valve migrated and was embolized during recovery of the delivery device; the Salus valve was surgically explanted and sutured to the inner wall of the main pulmonary artery. At a mean follow-up of (5.5 ± 1.1) months, dysfunction or migration of the Salus valve embolism was not observed.Conclusions::This early feasibility study demonstrates the feasibility, safety, and effectiveness of transthoracic implantation of a Salus valve in patients with moderate-to-severe PR after NRVOT reconstruction. The short-term effectiveness is clear, medium and long-term effectiveness requires longer follow-up.

Objective::The size and morphology of the right ventricular outflow tract (RVOT) in patients suffering from long-term pulmonary regurgitation (PR) after native RVOT (NRVOT) reconstruction are important factors affecting the feasibility, safety, and effectiveness of transcatheter pulmonary valve replacement. The purpose of this study was to evaluate the feasibility, safety, and effectiveness of a transthoracic Salus valve (Balance Medical Technology Co., Ltd, Beijing, China) in patients with moderate-to-severe PR after NRVOT reconstruction.Methods::Patients with moderate-to-severe PR after NRVOT reconstruction were selected between June 2021 and November 2021 at Beijing Anzhen Hospital. Demographic data as well as preoperative, intraoperative, and follow-up data were reviewed.Results::Ten patients with moderate-to-severe PR after NRVOT reconstruction underwent physical examination, transthoracic echocardiography, and cardiovascular magnetic resonance imaging. Seven patients were selected for transthoracic Salus valve replacement. Six patients underwent implantation of the Salus valve successfully. One valve migrated and was embolized during recovery of the delivery device; the Salus valve was surgically explanted and sutured to the inner wall of the main pulmonary artery. At a mean follow-up of (5.5 ± 1.1) months, dysfunction or migration of the Salus valve embolism was not observed.Conclusions::This early feasibility study demonstrates the feasibility, safety, and effectiveness of transthoracic implantation of a Salus valve in patients with moderate-to-severe PR after NRVOT reconstruction. The short-term effectiveness is clear, medium and long-term effectiveness requires longer follow-up.