ObjectiveTo analyze the characteristics of plantar pressure of diabetic patients during gait cycle, and to design a offloading insole with variable stiffness. MethodsThe plantar pressure experiment was carried out and a database including 157 subjects was established. The differences of plantar pressure distribution were analyzed among diabetic patients with and without peripheral neuropathy, and healthy people. The insole pressure area was divided, and porous units were filled in different insole areas according to the pressure gradient. The fed-calf-insole finite element model of diabetic patients was constructed. The simulation analysis of different insole schemes was carried out under the conditions of push-off, footheel-strike and dynamic neutrality posture, and to explore the most reasonable insole stiffness design. ResultsCompared with the healthy group, the percentage of peak pressure and high pressure in the left and right heel areas of diabetic neuropathy patients showed a decreasing trend, in which the left peak pressure was significantly reduced by 11% (P = 0.026) and the percentage of high pressure was significantly reduced by 9.8% (P = 0.02). When the porous elements of 2.5 MPa and 1.9 MPa were used in the high pressure area of the insole metatarsal and high pressure area of the heel, the peak plantar pressure of footheel-strike, dynamic neutral and push-off was reduced by 42.4%, 27.4% and 26.4%, and the peak stress of the soft tissue was reduced by 49.8%, 43.6% and 25.1%, respectively. ConclusionThere is a higher risk of ulcer in the metatarsal region than in the heel region for diabetic patients. The variable stiffness insoles based on the optimization of plantar pressure and internal stress under multi-posture can effectively reduce the peak pressure of plantar and peak stress of soft tissue during walking, which provides a reference for the design of variable stiffness insoles.

Objective An X-shaped cushioning insole with variable stiffness was designed to explore its effects on plantar pressure and internal stress of diabetic patients with toe amputation. Methods Based on CT images, the feet-calf finite element model of diabetic patients with toe amputation was established, and the insole was divided into different areas according to distribution characteristics of the planter pressure. The three-dimensional (3D) printed cushioning insole with an X-shaped sandwich structure was designed. The modulus of the sandwichstructure was changed by changing thickness of the sandwich structure panel. For simulation analysis, the divided area was filled with the X-shaped sandwich structure with different modulus. Results The peak plantar pressure of diabetic patients with toe amputation was in calcaneal region, and the combined insoles with 1. 2 mpanel thickness in toe area, 1. 4 mm panel thickness in metatarsal area, 2. 0 mm panel thickness in middle area and 1. 6 mm panel thickness in heel area had the best decompression effect. Compared with bare feet, the peak pressure in heel area of the insole, the peak pressure in phalangeal head area and the stress in plantar softissues were reduced by 40. 18% , 31. 7% , and 50. 44% , respectively. Conclusions The 3D printed insoles with variable stiffness can effectively reduce surface pressure and internal stress of the sole and reduce probability of the 2nd toe amputation

Objective:To standardize the management of pediatric Investigator-Initiated Trails (IIT) and improve the execution quality, this study takes a tertiary hospital for children in Shanghai as an example to analyze and summarize the main quality problems in the implementation of pediatric IIT projects and provide appropriate suggestions.Methods:From 2020 to 2022, based on the quality indicators of the IIT project of Shanghai Jiao Tong University School of Medicine, and combined with the characteristics of pediatrics, a centralized monitoring method was used to conduct spot checks and evaluations on the IIT project of a tertiary hospital for children in Shanghai.Results:From 2020 to 2022, a total of 77 IIT projects were inspected, including 27 in the initiation stage, 36 in the execution stage, and 14 in the conclusion stage. In terms of ethical compliance, there are issues with researchers′ weak ethical awareness and non-standard signing of informed consent in the pediatric IIT project. The main problems in terms of execution quality and science include non-standard CRF table design, insufficient awareness of safety management, lack of emphasis on research registration and specialized data management, randomization and blind methods. There are issues with low enrollment rate and low funding execution rate in terms of execution progress.Conclusions:There are certain quality problems during the execution of pediatric IIT projects. Strengthen the establishment of an effective process management and supervision system to improve the quality management of pediatric IIT research processes is needed.

Objective:To evaluate the distribution and drug sensitivity of pathogenic bacteria in patients with bacterial keratitis in recent 40 years in China.Methods:A Meta-analysis was conducted.Five databases including PubMed, ScienceDirect, Embase, CNKI and Wanfang Data Knowledge Service Platform were searched.The research was limited to the hospital-based cross-sectional studies published in Chinese and English between 1980 and 2020, without limitations of subject.Two researchers followed the inclusion and exclusion criteria to complete literature retrieval, data extraction and methodological quality evaluation.The literature quality was assessed with reference to a methodological scoring system for rates. Q test and I2 test were used to quantify the degree of heterogeneity of the included literature.According to the heterogeneity, the fixed effects model or random-effects model was used to calculate the combined rates indicators to perform the Meta-analysis. Results:Twenty-seven original studies were incorporated, including 50 046 cases of bacterial keratitis.A random-effects model for the Meta-analysis showed that the positive rate of bacterial culture in bacterial keratitis was 28% (95% CI: 0.24-0.32). Among the culture-positive bacteria, the percentages of gram-positive cocci and gram-negative bacilli were 57% (95% CI: 0.52-0.62) and 32% (95% CI: 0.28-0.37), respectively.The percentages of gram-positive bacilli and gram-negative cocci were 8% (95% CI: 0.06-0.10) and 1% (95% CI: 0.01-0.02), respectively.In the recent 40 years, the proportion of gram-positive cocci isolated from corneas in China was on the rise, and the proportion of gram-negative bacilli was on the decline.Among them, coagulase-negative Staphylococcus accounted for 23% (95% CI: 0.17-0.30), followed by Pseudomonas aeruginosa 18% (95% CI: 0.14-0.23), Streptococcus pneumoniae 8% (95% CI: 0.06-0.12), Staphylococcus aureus 6% (95% CI: 0.04-0.08), Corynebacterium 4% (95% CI: 0.03-0.07), and Escherichia coli 4% (95% CI: 0.02-0.06). The results of the drug sensitivity test showed that gram-positive cocci were highly sensitive to vancomycin, moxifloxacin, levofloxacin and ofloxacin. Pseudomonas aeruginosa was most sensitive to tobramycin, and Escherichia coli was most sensitive to ofloxacin. Conclusions:This Meta-analysis indicates that the proportion of gram-positive cocci isolated from corneas in China has been on the rise, while the proportion of gram-negative bacilli was on the decline during the recent 40 years.Coagulase-negative Staphylococcus and Pseudomonas aeruginosa have become the most common pathogens of bacterial keratitis in China.The sensitivity of various bacteria to commonly used antibiotics shows a downward trend.The sensitive antibiotics should be selected correctly according to the drug sensitivity results.

Objective Aiming at the problem that mechanical properties for the continuum of muscle tissues cannot be considered in active and passive behaviors of different structurally coupled muscles, a method of passive and active coupling in the same constitutive equation was proposed to construct ahyperelastic active and passive constitutive model of skeletal muscle continuum. Methods In order to calibrate parameters of the passive constitutive model, the uniaxial tensile experiment method and conditions were given, and through theoretical derivation, the specific method of using experimental data to solve the passive model parameters was introduced. In order to verify effectiveness of the active model, the model was verified with an example. Results The curves predicted by the model were in good agreement with the experimental output stress-stretch ratio curves. At the same strain, the maximum error of passive stress and total stress were only 20 kPa and 40 kPa. Conclusions The continuum hyperelastic constitutive model can better simulate active and passive behavior of skeletal muscles, which is beneficial for modeling and simulation of human muscles in further study.

Inflammatory immune response runs through the course of ischemic stroke. Different subgroups of CD4 + T cells play a complex and important role in the course of ischemic stroke. Among them, the balance of pro-inflammatory effect of T helper cell 17 (Th17) and anti-inflammatory effect of regulatory T cells (Treg) is closely associated with the outcome of stroke. This article reviews the role of Th17/Treg balance in ischemic stroke, in order to deepen the understanding of the mechanism of immune inflammation after ischemic stroke and explore possible therapeutic targets in the course of ischemic stroke.

The clinical data of a newborn with Kleefstra syndrome combined with SLC2A1 gene mutation in the Department of Newborn Infants, Children′s Hospital of Nanjing Medical University were retrospectively analyzed.The laboratory examination, genetic characteristics, diagnosis and treatment progress were analyzed.This is the first report of a newborn with Kleefstra syndrome combined with SLC2A1 gene mutation, presenting with an early-onset epilepsy.Gene analysis is the most reliable method to make a definitive diagnosis.

Objective:To investigate the regulatory effects of sphingosine kinase-2 (SphK2) on the function of activated astrocytes and the progression of experimental autoimmune encephalomyelitis (EAE) in mice.Methods:Primary mouse astrocytes were isolated from wild-type (WT) C57BL/6 mice and sphk2 gene knock-out ( sphk2 -/-) mice and stimulated in vitro with interleukin 17 (IL-17). Real-time PCR was used to measure the expression of inflammatory cytokines and chemokines at mRNA levels. Western blot and immunofluorescence were used to detect the expression of glial fibrillary acidic protein (GFAP) and the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3). An EAE mouse model was constructed using myelin oligodendrocyte glycoprotein 35-55 (MOG 35-55) polypeptide. Western blot was used to detect the expression of GFAP and p-STAT3 at protein level and real-time PCR was used to detect the expression of inflammatory cytokines and chemokines at mRNA level in spinal cords. Hematoxylin-Eosin (HE) and Luxol fast blue (LFB) staining were used to observe the changes in inflammatory cell infiltration and demyelination in spinal cords. Results:Compared with the WT group, the phosphorylation of STAT3 was obviously reduced in in vitro activated mouse astrocytes of sphk2 -/- mice, and the expression of inflammatory cytokines and chemokines including monocyte chemotactic protein 1 (MCP-1), TNF-α and IL-6 at mRNA level was also significantly decreased. Compared with the WT EAE group, changes in the above-mentioned cytokines and relative proteins in sphk2 -/- EAE mice in vivo were similar to those in vitro. Moreover, inflammatory cell infiltration and demyelination were significantly reduced in spinal cords of sphk2 -/- EAE mice. However, no significant difference in in vitro or in vivo GFAP expression was observed between WT and sphk2 -/- mice. Conclusions:SphK2 might regulate the function of reactive astrocytes through STAT3 molecular pathway, thereby regulating the production of inflammatory cytokines and chemokines and participating in the pathological process of EAE.

Objective To evaluate the role of sarcolemmal ATP-sensitive potassium ( sarcKATP ) channel in sevoflurane-induced maintenance of electrophysiological stability of ventricular myocardium in di-abetic rats. Methods Clean-grade healthy male Sprague-Dawley rats, aged 3 months, weighing 280-320 g, in which diabetes mellitus ( DM) was induced by intraperitoneal streptozotocin 60 mg/kg and confirmed by blood glucose ≥16. 7 mmol/L, were used in this study. Their hearts were excised after anesthesia and retrogradely perfused in a Langendorff apparatus at 4 weeks after establishing the DM model. Twenty-four Langendorff-perfused hearts were divided into 3 groups ( n=8 each) using a random number table method:DM group ( group D) , DM plus sevoflurane group ( group DS) and DM plus sevoflurane plus HMR-1098 group (group DSH). Another 8 Langendorff-perfused hearts of normal rats were selected as control group ( group C) . Hearts were perfused with 37℃ K-H solution via the aorta in each group, 15 min of equilibra-tion later hearts were continuously perfused for 30 min with K-H solution in C and D groups, with K-H solu-tion saturated with 2. 5％ sevoflurane in group DS, or with K-H solution saturated with 10 μmol/L HMR-1098 and 2. 5％ sevoflurane in group DSH. Monophasic action potential (MAP) duration at 50％ and 90％repolarization ( MAPD50 and MAPD90 ) in the endocardium and epicardium of the left ventricular anterior wall were recorded at 15 min of equilibration ( T0 ) and 15 and 30 min of reperfusion ( T1,2 ) , transmural dispersion of repolarization ( TDR) was calculated. S1S2 program-controlled stimulation was performed at the end of perfusion to record the effective refractory period (ERP), ventricular arrhythmia (VA) induced and the longest pacing cycle length ( PCL) of ventricular fibrillation threshold ( VFT) induced. ERP/MAPD90 ratio was calculated. Results Compared with group C, TDR was significantly increased at T0 , ERP/MADP90 ratio was decreased, the incidence of VA induced was increased, and the longest PCL of VFT induced was prolonged in group D ( P＜0. 05) . Compared with group D, TDR was significantly decreased at T2 in group DS (P＜0. 05), and ERP/MADP90 ratio was significantly increased, the incidence of VA in-duced was decreased, and the longest PCL of VFT induced was shortened in DS and DSH groups ( P＜0. 05). TDR was significantly smaller at T2 in group DSH than in group DS (P＜0. 05). Conclusion sarcKATP channel is involved in sevoflurane-induced maintenance of electrophysiological stability of ventricu-lar myocardium in diabetic rats.

Objective: To evaluate the effect of sevoflurane on phosphorylation of connexin 43 (Cx43) at Ser368 (Cx43 Ser368) in ventricular myocardium in isolated hearts of diabetic rats. Methods: Twenty-four clean-grade healthy adult male Sprague-Dawley rats, aged 3 months, weighing 180-220 g, were used in this study.The diabetic model was established by intraperitoneally injecting streptozotocin 60 mg/kg.The hearts were rapidly excised and retrogradely perfused with K-H solution saturated with 95% O₂-5% CO₂ at 37 ℃ in a Langendorff apparatus.Sixteen Langendorff-perfused diabetic hearts were divided into 3 groups (n=8 each) using a random number table method: diabetes mellitus group (group D) and sevoflurane group (group DS). Another 8 Langendorff-perfused normal hearts of rats were selected and served as control group (group C). After 15 min equilibration with K-H solution, the hearts were continuously perfused for 30 min with K-H solution in group C and group D and with K-H solution saturated with 2.5% sevoflurane in group DS.S1S2 program-controlled stimulation was performed at the end of perfusion, the occurrence of induced ventricular arrhythmia (VA) and the maximal pacing cycle length (PCL) of induced VA were recorded, and conduction velocity (CV) was calculated.The expression of phosphorylated Cx43 at Ser368 (p-Cx43 Ser368) in ventricular myocytes was determined by Western blot. Results: Compared with group C, the incidence of induced VA was significantly increased, the maximal PCL of induced VA was prolonged, the CV was decreased, and the expression of p-Cx43 Ser368 was up-regulated in group D (P<0.05). Compared with the incidence of induced VA was significantly decreased, the maximal PCL of induced VA was shortened, the CV was increased, and the expression of p-Cx43 Ser368 was down-regulated in group DS (P<0.05). Conclusion The mechanism by which sevoflurane stabilizes the ventricular electrical conduction is associated with decreasing the phosphorylation of Cx43 at Ser368 in diabetic rats.