BACKGROUND:Autologous bone,allogeneic bone or artificial bone has been used to promote bone defect repair in the clinic,but the rate of non-healing is still high.The key is to ignore the importance of periosteum in the bone healing process.In the early stage of the project,the project team constructed an electrospinning membrane loaded with vascular endothelial growth factor to highly simulate the intramembranous osteogenesis of natural periosteum at the bone defect site,which promoted bone regeneration to a certain extent.However,the injured area often faces the dilemma of severe inflammatory response mediated by macrophages and lack of seed cells,resulting in the risk of inactivation or diffusion of delivered biological factors.Therefore,it is necessary to further optimize and coordinate the immune regulation and angiogenesis functions of biomimetic periosteum to promote bone repair.OBJECTIVE:To investigate the physicochemical properties of stem cell-engineered bionic periosteum and its role in regulating the inflammatory microenvironment to promote bone repair.METHODS:By combining L-polylactic acid-based microsol electrospinning,type Ⅰ collagen self-assembly and gel stem cell transplantation technology,a bionic periosteum(M@C-B)was constructed,in which the core layer loaded with vascular endothelial growth factor and the shell layer delivered bone marrow mesenchymal stem cells to regulate the immune microenvironment of bone defects.The physicochemical properties of the periosteum were characterized by scanning electron microscopy,transmission electron microscopy,and Fourier transform infrared spectroscopy.A co-culture system was established between the bionic periosteum and macrophages,bone marrow mesenchymal stem cells and human umbilical vein endothelial cells to explore immune regulation and in vitro osteogenic and angiogenic abilities.Finally,the osteogenic properties of the stem cell engineered bionic periosteum were further verified in a rat femoral condyle defect model.RESULTS AND CONCLUSION:(1)Transmission electron microscopy results showed that the micro-sol electrospinning(MS)formed a distinct core-shell structure.Scanning electron microscopy indicated that after the assembly of the collagen-l artificial periosteum(M@C)on the surface of the vascular endothelial growth factor-loaded micro-sol,a distinct"spider web-like"fibrous structure was deposited.Infrared spectroscopy further confirmed the successful self-assembly of collagen-l.Release experiments demonstrated that the M@C group mitigated the burst release phenomenon compared to the MS group,maintaining internal vascular endothelial growth factor activity and sustained release.(2)Live/dead cell staining and CCK-8 assay showed that bone marrow mesenchymal stem cells proliferated well and survived on three types of artificial periosteum:MS,purely aligned poly(L-lactic acid)(PLLA)surface self-assembled collagen-l artificial periosteum(PLLA@C),and vascular endothelial growth factor-loaded micro-sol fiber surface self-assembled collagen-l-bone marrow mesenchymal stem cells artificial periosteum(M@C-B).Among them,the M@C-B group had the highest number of live cells and the fastest proliferation rate.(3)Alkaline phosphatase staining,alizarin red staining,and osteopontin immunofluorescence staining showed that the PLLA@C and M@C-B groups significantly promoted osteogenic differentiation of bone marrow mesenchymal stem cells.Angiogenesis experiments demonstrated that the vascular endothelial growth factor-loaded groups(MS and M@C-B)had longer blood vessel lengths and more reticular vascular-like structures with more cross-linked nodes,with the M@C-B group being the most prominent.(4)Immunofluorescence and flow cytometry showed that artificial periosteum in the M@C-B group significantly inhibited the pro-inflammatory macrophage phenotype and promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype.(5)In vivo studies further confirmed that the M@C-B group showed superior bone mineral density,trabecular thickness,relative bone volume,and trabecular spacing compared to other groups.(6)These results indicate that bone marrow mesenchymal stem cell-engineered artificial periosteum,through the rapid regulation of the bone defect immune microenvironment by the collagen-l-bone marrow mesenchymal stem cells outer phase and the sustained release of vascular endothelial growth factor by the micro-sol electrospinning core-shell structure of the inner phase,synergistically promotes bone healing.

BACKGROUND:Autologous bone,allogeneic bone or artificial bone has been used to promote bone defect repair in the clinic,but the rate of non-healing is still high.The key is to ignore the importance of periosteum in the bone healing process.In the early stage of the project,the project team constructed an electrospinning membrane loaded with vascular endothelial growth factor to highly simulate the intramembranous osteogenesis of natural periosteum at the bone defect site,which promoted bone regeneration to a certain extent.However,the injured area often faces the dilemma of severe inflammatory response mediated by macrophages and lack of seed cells,resulting in the risk of inactivation or diffusion of delivered biological factors.Therefore,it is necessary to further optimize and coordinate the immune regulation and angiogenesis functions of biomimetic periosteum to promote bone repair.OBJECTIVE:To investigate the physicochemical properties of stem cell-engineered bionic periosteum and its role in regulating the inflammatory microenvironment to promote bone repair.METHODS:By combining L-polylactic acid-based microsol electrospinning,type Ⅰ collagen self-assembly and gel stem cell transplantation technology,a bionic periosteum(M@C-B)was constructed,in which the core layer loaded with vascular endothelial growth factor and the shell layer delivered bone marrow mesenchymal stem cells to regulate the immune microenvironment of bone defects.The physicochemical properties of the periosteum were characterized by scanning electron microscopy,transmission electron microscopy,and Fourier transform infrared spectroscopy.A co-culture system was established between the bionic periosteum and macrophages,bone marrow mesenchymal stem cells and human umbilical vein endothelial cells to explore immune regulation and in vitro osteogenic and angiogenic abilities.Finally,the osteogenic properties of the stem cell engineered bionic periosteum were further verified in a rat femoral condyle defect model.RESULTS AND CONCLUSION:(1)Transmission electron microscopy results showed that the micro-sol electrospinning(MS)formed a distinct core-shell structure.Scanning electron microscopy indicated that after the assembly of the collagen-l artificial periosteum(M@C)on the surface of the vascular endothelial growth factor-loaded micro-sol,a distinct"spider web-like"fibrous structure was deposited.Infrared spectroscopy further confirmed the successful self-assembly of collagen-l.Release experiments demonstrated that the M@C group mitigated the burst release phenomenon compared to the MS group,maintaining internal vascular endothelial growth factor activity and sustained release.(2)Live/dead cell staining and CCK-8 assay showed that bone marrow mesenchymal stem cells proliferated well and survived on three types of artificial periosteum:MS,purely aligned poly(L-lactic acid)(PLLA)surface self-assembled collagen-l artificial periosteum(PLLA@C),and vascular endothelial growth factor-loaded micro-sol fiber surface self-assembled collagen-l-bone marrow mesenchymal stem cells artificial periosteum(M@C-B).Among them,the M@C-B group had the highest number of live cells and the fastest proliferation rate.(3)Alkaline phosphatase staining,alizarin red staining,and osteopontin immunofluorescence staining showed that the PLLA@C and M@C-B groups significantly promoted osteogenic differentiation of bone marrow mesenchymal stem cells.Angiogenesis experiments demonstrated that the vascular endothelial growth factor-loaded groups(MS and M@C-B)had longer blood vessel lengths and more reticular vascular-like structures with more cross-linked nodes,with the M@C-B group being the most prominent.(4)Immunofluorescence and flow cytometry showed that artificial periosteum in the M@C-B group significantly inhibited the pro-inflammatory macrophage phenotype and promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype.(5)In vivo studies further confirmed that the M@C-B group showed superior bone mineral density,trabecular thickness,relative bone volume,and trabecular spacing compared to other groups.(6)These results indicate that bone marrow mesenchymal stem cell-engineered artificial periosteum,through the rapid regulation of the bone defect immune microenvironment by the collagen-l-bone marrow mesenchymal stem cells outer phase and the sustained release of vascular endothelial growth factor by the micro-sol electrospinning core-shell structure of the inner phase,synergistically promotes bone healing.

Objective To summarize the potential risk factors that may arise in the national drug sampling and testing inspection process in recent years,to focuse on the operation of the quality management system,and to put forward proposals on how to do a good job under the new drug regulatory model of sampling and testing work.Methods Focusing on the investigation of data integrity and authenticity,the analysis focuses on the analysis of risk points such as reagent management,standard substance management,instrument,and facility management,electronic data management and other issues,and carries out a comprehensive verification of the effectiveness of the operation of the quality management system and so on.Results National drug sampling and testing institutes should strengthen the overall quality management,according to the operation of the laboratory,combined with their respective risk characteristics,reagent management,standard substance management,instrument and facility management,electronic data management and other aspects of the risk of systematic sorting and the establishment of the risk alert function,the development of risk warning lists,and the implementation of the corresponding risk control strategy.Conclusion National drug sampling and testing institutes must strengthen the operation of the process of influencing factors in the effective control of the emphasis on the testing of the work of the key control points and continue to standardize and improve the inspection process of the quality system to ensure that the quality of the various activities in a controlled state.

To summarize the nursing experience of a patient with relapsed/refractory diffuse large B-cell lymphoma who suffered from cytokine release syndrome after chimeric antigen receptor T-cell therapy.The main nursing experiences include:implementing emergency care for distributive shock caused by cytokine storm;carrying out the nursing of lung ventilation protection strategies;strengthening detailed skin care;prevention,control and care of hospital-acquired infections in an immunosuppressed state.After active treatment,the patient was transferred to the general ward 9 days later and discharged 27 days later.

Objective To analyze the epidemiological burden of age-related macular degeneration(AMD)in China and low-,middle-,and high-socio-demographic index(SDI)countries,thereby providing a theoretical foundation for the prevention and control of AMD.Methods The data published by Global Burden of Disease(GBD)from 1990 to 2021,in-cluding the number of cases,prevalence,disability-adjusted life years(DALYs),and DALYs rate,were utilized to analyze the characteristics of AMD in China and low-,middle-,and high-SDI countries and assess the burden of AMD and its corre-lation with SDI.Results In 2021,the number of patients with AMD and DALYs in China ranked first in the world.Be-sides,the age-standardized prevalence rate(ASPR)and age-standardized DALYs rate(ASDR)in China ranked 46th and 64th in the world,respectively.The number of patients with AMD and DALYs in high-SDI countries were significantly lower than those in middle-and low-SDI countries.The ASPR and ASDR in China were higher than those in high-SDI countries but lower than those in low-SDI countries,and both exceeded the global averages.The prevalence of AMD among people aged 55 years and above was significantly higher.In high-SDI countries,the highest prevalence of AMD was observed a-mong people aged 80 years or above.The prevalence of AMD in China and middle-SDI countries peaked among people aged 65-69 years;whereas that in low-SDI countries peaked among people aged 75-79 years.The AMD burden in females was significantly higher than that in males.The global number of AMD patients exhibited an increasing trend from 1990 to 2021,with the fastest increase observed in China(3.11-fold).The ASPR in China showed a wave-like increasing trend,while that in low-,middle-,and high-SDI countries showed a decreasing trend during the same period.The overall DALY showed an increasing trend,and the increase in the DALYs in China(2.84-fold)exceeded that in low-,middle-,and high-SDI countries.However,the overall ASDR declined,with the most significant decline observed in high-SDI countries.The AS-DR in China has recently rebounded after a wave-like decline from 1990 to 2021.The analysis results of the slope index of inequality(SII)and concentration index(CI)showed that the gap in the AMD burden between high-income and low-in-come countries widened progressively from 1990 to 2021,with the burden being more severe in low-SDI countries.Conclu-sion In 2021,the number of patients with AMD and DALYs in China ranked first in the world.The overall disease burden of AMD in China was between that of high-and low-SDI countries but was higher than global averages.The prevalence of AMD among people aged 55 years and above was significantly higher,and the burden was higher for females than for males.From 1990 to 2021,the number of patients with AMD and the prevalence of this disease in China exhibited an in-creasing trend,while those in low-,middle-,and high-SDI countries showed a decreasing trend.The overall DALYs in-creased,while the overall ASDR decreased.The gap in the AMD burden between high-income and low-income countries widened,and the burden was more severe in low-SDI countries.It was concluded that the burden of AMD was closely re-lated to age,gender,and SDI,and that its distribution characteristics and trends should be considered in the formulation of prevention and control strategies.

Ocular trauma is a leading cause of permanent visual impairment and loss of working a-bility.Among them,orbital foreign body injuries are often accompanied by multiple injuries to the eye-ball and surrounding tissues,adversely affecting the quality of life.This paper reported a 33-year-old male patient with right orbital foreign body resulting in eyeball contusion,extraocular muscle injury,and restricted ocular movement.After surgical removal of the foreign body combined with integrated traditional Chinese and western medicine treatment,the patient's visual acuity improved from 0.4 to 0.8,and ocular motility function significantly improved.This suggests that comprehensive treatment contributes to promoting functional recovery and enhancing clinical efficacy.

Objective To assess the global,regional,and national burdens of eye cancer between 1990 and 2021,examine its change trends with the age,sex,geographic location,and socio-demographic index(SDI)level,and provide scientific evidence for the development of eye cancer prevention and control strategies.Methods Based on the data from the Global Burden of Disease(GBD)study,the global burden of eye cancer was evaluated using the indicator system inclu-ding incidence,prevalence,mortality,and disability-adjusted life years(DALYs).The change trend of the burden of eye cancer with time was quantified with Join-point regression.Frontier analysis methods were used to evaluate the relationship between the burdens of eye cancer with SDI.Results From 1990 to 2021,the global incidence,age-standardized inci-dence rate(ASIR),prevalence and age-standardized prevalence rate(ASPR)of eye cancer showed an upward trend over time.Conversely,the mortality,age-standardized mortality rate(ASMR),DALYs,and age-standardized DALY rate(ASDR)declined during the same period.All the above indicators in males were higher than those in females.Regionally,Eastern Sub-Saharan Africa bore the highest disease burden,while Oceania had the lowest.It should be noted that East Asia experienced the most significant increase in ASIR,and Southern Sub-Saharan Africa showed the greatest rise in ASPR.Meanwhile,Southern Latin America demonstrated the most pronounced decrease in both ASIR and ASPR.East Asia also re-corded the largest reductions in ASMR and ASDR.At the national level,Malawi had the highest disease burden in 2021.To-kelau exhibited the most substantial increase while Norway showed the greatest decrease in disease burden.Age-specific analysis revealed a bimodal distribution,with children under 5 years and adults over 80 being the most affected groups.Furthermore,SDI-based analysis indicated a wave-like relationship between SDI and ASIR/ASPR,and both ASMR and AS-DR declined with the increasing SDI.Conclusion The global burden of eye cancer shows a decline trend generally.The difference in the burden of eye cancer between regional and national levels may be related to medical resource allocation and public health policies.The results of this study provide scientific evidence for the development of tailored eye cancer prevention and control strategies.It is recommended that more attention should be paid to high-burden regions,resource distribution should be optimized,early screening should be enhanced,and targeted interventions for different age and gen-der groups should be implemented.

Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.

Objective:To analyze the effects of the disease and injury spectrum on health-adjusted life expectancy (HALE) among permanent residents aged 55 and above in Shenzhen from 2016 to 2030.Methods:Based on the mortality surveillance data and the permanent resident population data in Shenzhen from 2016 to 2022, the Sullivan method was used to calculate the HALE during 2016—2022. The Bayesian age-period-cohort model and the grey system model were used to predict the HALE during 2023—2030. The HALE changes in the two periods were decomposed into the contributions of 20 categories of diseases and injuries, respectively.Results:From 2016 to 2022, the HALE increased from 31.41 years (95% CI: 30.50-32.32) to 33.57 years (95% CI: 32.47-34.67). During this period, the mortality effect of neurological disorders slowed the increase of HALE, with a reduction of 0.27 years. By 2030, it is anticipated that the HALE will reach 36.40 years (95% CI: 34.78-38.01). This is expected to be influenced by the mortality effects of nutritional deficiencies (-0.40 years) and mental disorders (-0.29 years), as well as the disability effects of musculoskeletal disorders (-0.66 years), skin and subcutaneous diseases (-0.21 years) and nutritional deficiencies (-0.13 years). Conclusion:The HALE of permanent residents aged 55 years and above in Shenzhen demonstrated an increasing trend over time. Greater attention should be paid to the adverse effects of neurological disorders, nutritional deficiencies, mental disorders, musculoskeletal disorders, and skin and subcutaneous diseases on the continuous increase of HALE in this population.

Objective To study the therapeutic effect of hypothermic perfusion fluid in manual small incision cataract surgery(MSICS).Methods A total of 60 elderly patients with hard cataracts undergoing MSICS at Nanjing Central Hospital(Nanjing Municipal Government Hospital)from January to September 2024 were selected as subjects,they were divided into hypothermic group(n=29)and normal temperature group(n=31)by using a random number table method.Hypothermic group received 4℃intraocular perfusion fluid during surgery,while normal temperature group received 22 ℃ intraocular perfusion fluid.The study compared differences in best corrected visual acuity(BCVA),intraocular pressure,endothelial cell density(ECD),and central macular thickness(CMT)between two groups before and after surgery.Postoperative ocular complications within three months were also recorded for both groups.Results Hypothermic group showed significantly higher ECD levels at 1 day postoperative,1 week postoperative,and 3-month postoperative compared to normal temperature group,with statistically significant differences(P＜0.05).Hypothermic group exhibited lower rates of corneal edema on day 1 postoperative,reduced macular edema incidence at 3-month follow-up,and overall lower incidence of complications than normal temperature group,the difference was statistically significant(P＜0.05).Conclusion The use of hypothermic perfusion fluid in MSICS treatment of senile hard corneal cataract can protect corneal endothelial cells,reduce early postoperative corneal edema,and significantly reduce the incidence of common postoperative complications.