BACKGROUND:As the incidence of spinal cord injury increases with the years and axon regeneration after spinal cord injury was very difficult.How to promote the recovery from spinal cord injury and improve the transplantation efficiency of stem cells and other therapeutic cells after spinal cord injury has been the focus of clinical and scientific research. OBJECTIVE:To establish the efficient transplantation and replacement of mouse spinal cord microglia in the spinal cord injury model. METHODS:CX3CR1 creER-/+::LSL-BDNF-/+-tdTomato mice,CX3CR1+/GFP mice,β-actin GFP mice and C57 BL/6J wild-type mice at 8-10 weeks of age were selected.According to the requirements of the experiment,they were randomly divided into six groups.(1)Sham operation group:eight C57 BL/6J wild-type mice were used when only the lamina was removed without injury.(2)Spinal cord contusion injury group:eight C57 BL/6J wild-type mice were used.(3)Spinal cord crush injury group:eight C57 BL/6J wild-type mice were used.(4)Conjoined symbiotic spinal cord strike injury group:β-actin GFP mice with green fluorescent blood were surgically stitched together with C57 BL/6J wild-type mice,using eight β-actin GFP mice and eight C57 BL/6J wild-type mice.(5)Mr BMT-X Ray group(using PLX5622 to eliminate the spinal microglia and bone marrow transplantation with X-ray radiation):Bone marrow cells from four CX3CR1 creER-/+::LSL-BDNF-/+-tdTomato mice were extracted and transplanted into eight C57 BL/6J wild-type mice for spinal cord injury modeling.(6)Mr BMT-Busulfan group(using PLX5622 to eliminate the spinal microglia and bone marrow transplantation with Busulfan):Bone marrow cells from four CX3CR1+/GFP mice were transplanted into eight C57 BL/6J wild-type mice.The percentage of cell transplantation replacement in this group was observed,and the spinal cord injury model was not established in this group.The sham operation group,spinal cord contusion injury group and spinal cord crush injury group were sampled by perfusion on day 14 after spinal cord injury.The conjoined symbiotic spinal cord strike injury group was sampled by perfusion on day 7 after spinal cord injury.Mr BMT-X Ray group was sampled by perfusion on day 28 after spinal cord injury.Mr BMT-Busulfan group was sampled by perfusion on day 28 after transplantation.The sampling site was a 1.2 cm long spinal cord with the T10 segment as the center.In the Mr BMT-X Ray group and Mr BMT-Busulfan group,additional mouse brain tissue was retained to see if it would lead to brain transplantation and replacement.The number and proportion of transplanted and replaced cells in the damaged area were measured using transgenic mice,symbiosis and immunofluorescence. RESULTS AND CONCLUSION:Compared with the traditional peripheral blood transplantation(9.8%)of mice in the conjoined symbiotic spinal cord strike injury group,the new transplantation methods,Mr BMT-X Ray and Mr BMT-Busulfan,could greatly improve the proportion of spinal microglia transplantation and replacement,which could reach 84.8%and 95.6%,respectively.The difference was significant(P<0.05).The results showed that Mr BMT-X Ray and Mr BMT-Busulfan could achieve efficient replacement of spinal microglia cells,and could improve the problems of low cell transplantation efficiency,few survival numbers and unclear differentiation of the traditional cell transplantation methods.In addition,Mr BMT-X Ray can only replace the microglia in the spinal cord,while Mr BMT-Busulfan could avoid brain inflammation and injury caused by X-ray radiation transplantation.

Objective:In order to construct a multisectoral cooperation evaluation index system for chronic disease prevention and control in the Healthy China strategy,so as to provide a reference for the evaluation and improvement of multisectoral cooperation work.Methods:The initial indicator system was constructed based on D'Amour's cooperative structure model.Fifteen public health experts were selected to refine the evaluation indicators through two rounds of expert consultation using the Delphi method.Then weights of indicators were assigned according to AHP.Results:Experts'positive coefficient,level of authority and coordination of opinions were confirmed.The finalized evaluation index system for multisectoral cooperation in chronic disease prevention and control contains 5 first-level indicators,12 second-level indicators and 34 third-level indicators.According to the weight,the indicators in first level were Shared Goals and Vision(0.222 8),Internalization(0.158 7),Formalization(0.252 3),Governance(0.154 5)and Cooperation effects(0.211 8).Conclusions:The evaluation index system applicable to multisectoral cooperation in the prevention and control of chronic diseases in counties(cities/districts)is preliminarily established,which is highly scientific and operable,and lays the foundation for the next step of application and promotion.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Despite growing prevalence and incidence, the management of gout remains suboptimal. The intermittent nature of the gout makes the long-term urate-lowering therapy (ULT) particularly important for gout management. However, patients are reluctant to take medication day after day to manage incurable occasional gout flares, and suffer from possible long-term toxicity. Therefore, a safe and easy-to-operate drug delivery system with simple preparation for the long-term management of gout is very necessary. Here, a chitosan-containing sustained-release microneedle system co-loaded with colchicine and uricase liposomes were fabricated to achieve this goal. This microneedle system was confirmed to successfully deliver the drug to the skin and maintain a one-week drug retention. Furthermore, its powerful therapeutic potency to manage gout was investigated in both acute gouty and chronic gouty models. Besides, the drug co-delivery system could help avoid long-term daily oral colchicine, a drug with a narrow therapeutic index. This system also avoids mass injection of uricase by improving its stability, enhancing the clinical application value of uricase. In general, this two-drug system reduces the dosage of uricase and colchicine and improves the patient's compliance, which has a strong clinical translation.

Objective: To compare the characteristics of children's pulmonary tuberculosis (PTB) cases reported from 2019 to 2021 before and during the implementation of the Action Plan to Stop Tuberculosis. Methods: Based on the reported incidence data and population data of child pulmonary tuberculosis (PTB) notified to the Chinese Center for Disease Control and Prevention (CDC) Tuberculosis Information Management System (TBIMS) from 2019 to 2021, the population information and clinically relevant information in different years were compared. Results: From 2019 to 2021, the reported cases of PTB in children were 363, 664 and 655, respectively. The number of reported cases increased significantly. The median age of the cases in children increased from 10.4 years in 2019 to 11.7 years in 2021 (P=0.005) over a three-year period. The etiological positive rate increased significantly from 11.6% (42/363) in 2019 to 32.2% (211/655) in 2021 (P<0.001). The positive rate of molecular testing increased most significantly, which became the main means of etiological detection and accounted for 16.7% (7/42), 62.0% (57/92) and 75.4% (159/211) of the children with positive etiological results, respectively. The resistance rates of isoniazid and rifampicin were analyzed in children with PTB who underwent drug sensitivity tests. The results showed that the resistance rates of isoniazid and/or rifampicin were 2/9, 3.9% (2/51) and 6.7% (11/163), respectively, with an average of 6.7% (15/223) over three years. The median patients' delay was 27 (12, 49) days in 2019. It was reduced to 19 (10, 37) days in 2020 and 15 (7, 34) days in 2021, both significantly lower than 2019 (P=0.009 and 0.000 2, respectively). Conclusion: From 2019 to 2021, the reported numbers of children with PTB and children with positive etiological results increase significantly in Liangshan Prefecture, while the diagnosis delay of patients significantly reduces.
Humans ; Child ; Rifampin/therapeutic use* ; Isoniazid/therapeutic use* ; Tuberculosis, Pulmonary/drug therapy* ; Tuberculosis ; China/epidemiology*

Objective: To compare the characteristics of children's pulmonary tuberculosis (PTB) cases reported from 2019 to 2021 before and during the implementation of the Action Plan to Stop Tuberculosis. Methods: Based on the reported incidence data and population data of child pulmonary tuberculosis (PTB) notified to the Chinese Center for Disease Control and Prevention (CDC) Tuberculosis Information Management System (TBIMS) from 2019 to 2021, the population information and clinically relevant information in different years were compared. Results: From 2019 to 2021, the reported cases of PTB in children were 363, 664 and 655, respectively. The number of reported cases increased significantly. The median age of the cases in children increased from 10.4 years in 2019 to 11.7 years in 2021 (P=0.005) over a three-year period. The etiological positive rate increased significantly from 11.6% (42/363) in 2019 to 32.2% (211/655) in 2021 (P<0.001). The positive rate of molecular testing increased most significantly, which became the main means of etiological detection and accounted for 16.7% (7/42), 62.0% (57/92) and 75.4% (159/211) of the children with positive etiological results, respectively. The resistance rates of isoniazid and rifampicin were analyzed in children with PTB who underwent drug sensitivity tests. The results showed that the resistance rates of isoniazid and/or rifampicin were 2/9, 3.9% (2/51) and 6.7% (11/163), respectively, with an average of 6.7% (15/223) over three years. The median patients' delay was 27 (12, 49) days in 2019. It was reduced to 19 (10, 37) days in 2020 and 15 (7, 34) days in 2021, both significantly lower than 2019 (P=0.009 and 0.000 2, respectively). Conclusion: From 2019 to 2021, the reported numbers of children with PTB and children with positive etiological results increase significantly in Liangshan Prefecture, while the diagnosis delay of patients significantly reduces.
Humans ; Child ; Rifampin/therapeutic use* ; Isoniazid/therapeutic use* ; Tuberculosis, Pulmonary/drug therapy* ; Tuberculosis ; China/epidemiology*

Children with certain comorbidities and immunocompromising conditions are highly vulnerable to SARS-CoV-2 infection. Vaccination against SARS-CoV-2 is an important strategy to reduce death， critical illness and overall disease burden. With the evolving and increasing transmission of SARS-CoV-2， universal vaccination is essential to achieve this goal. Children with special medical conditions are considered as the priorities for SARS-CoV-2 vaccination. However， vaccine hesitancy towards the implementation of SARS-CoV-2 vaccination currently remains an urgent challenge. In order to promote the sustainable vaccination for those children in Shanghai as well as China， Shanghai municipal center for disease control and prevention， together with the national children’s medical center， children’s hospital of Fudan university and the expert group on immunization planning of the Shanghai preventive medicine association， organized a consensus expert working group to formulate the evidence-based recommendations and implementation suggestions for children with common chronic diseases， allergy history， diseases involving adverse events related to vaccination， and immunocompromising conditions， based on the published evidence of SARS-CoV-2 vaccination for populations and children with special medical conditions.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

This study aimed to identify the direct pharmacological targets of Jingfang Granules in treating infectious pneumonia via "target fishing" strategy. Moreover, the molecular mechanism of Jingfang Granules in treating infectious pneumonia was also investigated based on target-related pharmacological signaling pathways. First, the Jingfang Granules extract-bound magnetic nanoparticles were prepared, which were incubated with lipopolysaccharide(LPS)-induced mouse pneumonia tissue lysates. The captured proteins were analyzed by high-resolution mass spectrometry(HRMS), and the target groups with specific binding to the Jingfang Granules extract were screened out. Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis was used to identify the target protein-associated signaling pathways. On this basis, the LPS-induced mouse model of infectious pneumonia was established. The possible biological functions of target proteins were verified by hematoxylin-eosin(HE) staining and immunohistochemical assay. A total of 186 Jingfang Granules-specific binding proteins were identified from lung tissues. KEGG pathway enrichment analysis showed that the target protein-associated signaling pathways mainly included Salmonella infection, vascular and pulmonary epithelial adherens junction, ribosomal viral replication, viral endocytosis, and fatty acid degradation. The target functions of Jingfang Granules were related to pulmonary inflammation and immunity, pulmonary energy metabolism, pulmonary microcirculation, and viral infection. Based on the in vivo inflammation model, Jingfang Granules significantly improved the alveolar structure of the LPS-induced mouse model of infectious pneumonia and down-regulated the expressions of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6). Meanwhile, Jingfang Gra-nules significantly up-regulated the expressions of key proteins of mitochondrial function COX Ⅳ and ATP, microcirculation-related proteins CD31 and Occludin, and proteins associated with viral infection DDX21 and DDX3. These results suggest that Jingfang Gra-nules can inhibit lung inflammation, improve lung energy metabolism and pulmonary microcirculation, resist virus infection, thus playing a protective role in the lung. This study systematically explains the molecular mechanism of Jingfang Granules in the treatment of respiratory inflammation from the perspective of target-signaling pathway-pharmacological efficacy, thereby providing key information for clinical rational use of Jingfang Granules and expanding potential pharmacological application.
Animals ; Mice ; Lipopolysaccharides ; Pneumonia ; Inflammation ; Anti-Infective Agents ; Biological Assay ; Disease Models, Animal ; Interleukin-6

Growth hormone deficiency (GHD) has become a serious healthcare burden, and presents a huge impact on the physical and mental health of patients. Here, we developed an actively separated microneedle patch (PAA/NaHCO₃-Silk MN) based on silk protein for sustained release of recombinant human growth hormone (rhGH). Silk protein, as a friendly carrier material for proteins, could be constructed in mild full-water conditions and ensure the activity of rhGH. After manually pressing PAA/NaHCO₃-Silk MN patch to skin for 1 min, active separation is achieved by absorbing the interstitial fluid (ISF) to trigger HCO₃ ^‒ in the active backing layer to produce carbon dioxide gas (CO₂). In rats, the MN patch could maintain the sustained release of rhGH for more than 7 days, and produce similar effects as daily subcutaneous (S.C.) injections of rhGH in promoting height and weight with well tolerated. Moreover, the PAA/NaHCO₃-Silk MN patch with the potential of painless self-administration, does not require cold chain transportation and storage possess great economic benefits. Overall, the PAA/NaHCO₃-Silk MN patch can significantly improve patient compliance and increase the availability of drugs, meet current unmet clinical needs, improve clinical treatment effects of GHD patients.