Objective: To investigate the trend in disease burden of injuries among children and adolescents in China from 1990 to 2021, so as to provide a basis for formulating prevention and control strategies and reducing this disease burden. Methods: Data on mortality, disability-adjusted life years (DALY) rate, incidence, and prevalence of injuries among children and adolescents aged <20 years in China from 1990 to 2021 were collected from the Global Burden of Disease (GBD) 2021 database. All rates were standardized using the GBD 2021 world standard population. The trend in incidence of disease burden of injuries among children and adolescents across differents genders and ages from 1990 to 2021 was evaluated using average annual percent change (AAPC). Results: From 1990 to 2021, the standardized mortality (AAPC=-5.435%), standardized DALY rate (AAPC=-5.311%), standardized incidence (AAPC=-0.466%), and standardized prevalence (AAPC=-0.810%) of injuries among children and adolescents in China showed downward trends (all P<0.05). Among these, the standardized mortality of animal contact (AAPC=-9.138%) and the standardized DALY rate of medical side effects (AAPC=-8.389%) decreased at a relatively fast pace, while the standardized incidence of falls (AAPC=0.083%) and the standardized prevalence of exposure to natural forces (AAPC=2.656%) showed upward trends (all P<0.05). The standardized mortality, standardized DALY rate, standardized incidence and standardized prevalence of injuries were higher in males than in females. The trend in males showed a downward trend (all P<0.05), consistent with the total population. The crude incidence of injuries in the group aged 15-<20 years showed an upward trend (AAPC=0.391%, P<0.05), while the trend in the group aged 10-<15 years was not statistically significant (P>0.05). The crude incidence of injuries in the groups aged 5-<10 years and <5 years showed downward trends (AAPC=-0.488% and -2.275%, both P<0.05). In 2021, the <5 years age group had the highest crude mortality and crude DALY rate of injuries, at 13.94/100 000 and 1 257.26/100 000, respectively. The 15-<20 years age group exhibited the highest crude incidence and crude prevalence, at 4 874.05/100 000and 4 050.35/100 000, respectively. Drowning and falls were major components of the disease burden across all age groups. Conclusions From 1990 to 2021, the disease burden of injuries among children and adolescents in China showed an overall downward trend. The disease burden was consistently higher in males than in females. Children aged <5 years face a high risk of fatality and disability, while adolescents aged 15-<20 years experience a high incidence and frequency of injuries. Drowning and falls were key priorities for prevention and control.

Objective:To explore the neuroprotective effects and mechanisms of memantine on sepsis-associated encephalopathy (SAE) model mice.Methods:Totally 90 male C57BL/6J mice aged 8-12 weeks were randomly divided into 3 groups (with 30 mice in each group) : sham group, model group and memantine group. The SAE mouse model was established by cecum ligation and puncture while mouse in sham group received open and closed abdomen only. The mice in the memantine group were irrigation with memantine (15 mg · kg -1· d -1) 3 hours before surgery and 7 consecutive days after modeling. The mice in the model group and sham group were irrigation with an equal volume of 0.9% sodium chloride solution. The 7-day survival rate was observed, neurobehavioral and cognitive function scores of each group of mice after modeling were assessed.Blood-brain barrier permeability was measured by detecting the content of Evans blue. Immunofluorescence staining was used to detect the expression of astrocytes. Enzyme linked immunosorbent assay was conducted to detect cellular inflammatory factors and the glutamic acid content detection kit was used to detect the expression of glutamic acid. All data were analyzed by Graphpad Prism 8.3.0 software, survival rate was analyzed using Kaplan-Meier survival curve.Multigroup comparisons were conducted by one-way ANOVA or Kruskal-Wallis test. Results:(1) There was a statistically significant difference in the 7-day survival rate among the three groups of mice after modeling ( F=24.11, P<0.01), and the 7-day survival rate of the memantine group was higher than that of the model group (57% (17/30), 27% (8/30), P<0.01). (2)The behavioral results showed that after 7 days of modeling, there were statistically significant differences in the total distance of the open field test, central area stay time, four corner area stay time, neurobehavioral scores, pole climbing test, and preference index for new object recognition test among the three groups of mice ( F/ χ2=17.67, 17.30, 9.39, 14.06, 10.36, 14.81, all P<0.05).The neurobehavioral score, pole climbing test score, preference index for new object recognition test, total distance of open field test, and central area stay time of the model group were all lower than those of the sham group (all P<0.05), while four corner area stay time of the model group was higher than that of the sham group ( P<0.05).The total distance of open field test (1 564.07(1 363.24, 1 988.19) cm, 913.91 (574.32, 1 096.23) cm), central area stay time (5.21 (4.91, 8.76) s, 1.09 (0.25, 1.64) s), neurobehavioral scores (9.75±0.50, 8.25±0.50), pole climbing test scores (5.67±0.52, 4.56±0.53), and preference index for new object recognition test (56.50±10.59, 26.84±2.91) of the memantine group were all higher than those of the model group (all P<0.05). The four corner area stay time was lower than that of the model group ((480.30±50.64) s, (529.80±36.20) s, P<0.05).(3)The comparison of molecular indicators showed that there were statistically significant differences in the content of Evans blue in the brain, the number of astrocytes in the hippocampus and cerebral cortex, pro-inflammatory cytokines (TNF-α、IL-1β、IL-6), anti-inflammatory cytokines (IL-10), and glutamic acid among the three groups of mice ( F/ χ2=8.84, 6.43, 28.46, 23.63, 12.23, 16.04, 69.22, 6.65, all P<0.05).The content of Evans blue, the number of astrocytes in the hippocampus and cerebral cortex, the expression of TNF-α、IL-1β、IL-6, and glutamate in the model group were all lower than those in the sham group(all P<0.05). The levels of IL-10 in the model group was lower than that in the sham group ( P<0.05).The content of Evans blue ((5.67±1.38)μg/g, (11.08±2.79)μg/g), the number of astrocytes in the hippocampus (16.50 (13.75, 22.25)/μm 2), 80.00 (73.50, 83.50)/μm 2) and the cerebral cortex (40.00 (29.00, 48.00)/μm 2, 81.50 (72.25, 89.00)/μm 2) in the memantine group were lower than those in the model group (all P<0.05).The pro-inflammatory factor TNF-α, IL-1β, IL-6 and glutamic acid expression in the memantine group were lower than those in the model group (all P<0.05), and the anti-inflammatory cytokine IL-10 was higher than that in the model group ( P<0.05). Conclusions:Memantine can improve the neurobehaviors and cognitive functions of SAE mice through improving the integrity of the damaged blood-brain barrier, alleviating inflammation in the brain, as well as reducing glutamate levels in the brain.

Objective To investigate the current status of frailty in patients on maintenance hemodialysis(MHD),and explore the correlation of frailty with anxiety and depression.Methods General information,clinical data and blood biochemical data of 101 cases who underwent MHD in Department of Nephrology,Shunde Hospital Affiliated to Jinan University from January 2023 to January 2024 were collected.FRAIL scale was applied to evaluate the frailty of the patients,and they were accordingly classified into frailty group and non-frailty group(including pre-frail and non-frail participants).Anxiety and depression were evaluated by GAD-7 and PHQ-9 scale.Univariate analysis and logistic regression were used to explore the association of frailty with anxiety,depression and other possible influencing factors.Results Among the 101 cases,29 cases(28.71%)were includedin frailty group and 72 cases(71.29%)in non-frailty group.There were 42 patients with depression(41.58%)and 25 with anxiety(24.75%).In the frailty group,the prevalence of depression was 65.52%and that of anxiety 55.17%.There were significant differences in age,grip strength,exercise,stroke and coronary heart disease,anxiety and depression,ferritin and CRP between the two groups(P＜0.01).Multivariate regression analysis showed that depression,anxi-ety,no exercise,stroke and high ferritin concentration were independent risk factors for frailty in MHD patients(P＜0.05).Conclusion In patients on MHD,frailty is closely associated with depression,anxiety,and lack of exercise,and stroke as well as high ferritin concentration are independent risk factors for frailty.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

BACKGROUND:Recent studies have shown that research on naringin anti-osteoporosis mostly stays in in vitro and in vivo experiments.Understanding the mechanism of related signaling pathways and the expression of related proteins and some specific genes is an important way to deeply understand naringin anti-osteoporosis.At present,traditional Chinese medicine has been confirmed to have a significant role in anti-osteoporosis.Naringin is one of the main active ingredients in Rhizoma Drynariae.Its effectiveness and mechanism of action against osteoporosis have been gradually recognized by scholars,and its clinical and basic research has been gradually emphasized. OBJECTIVE:To analyze and summarize the research progress of naringin in anti-osteoporosis in vitro and in vivo,thereby providing some ideas for the next step to study its related mechanism of action. METHODS:The relevant literatures included in CNKI and PubMed database were searched with the Chinese search terms of"naringin,osteoporosis,traditional Chinese medicine compound,pathogenesis,signaling pathway,bone marrow mesenchymal stem cells,osteoblasts,osteoclasts"in Chinese and English,respectively.The corresponding criteria were established according to the research needs,and finally 69 articles were included for review. RESULTS AND CONCLUSION:Naringin blocks the increase in the number of osteoclasts and adipocytes,the decrease in the number of osteocytes and osteocalcin(+)cells induced by fructose-rich diet,and promotes the secretion of Sema3A from osteoblasts and osteocytes,thereby enhancing local bone formation and inhibiting osteoclast production by activating the Wnt/β-catenin pathway.Naringin is an important way to induce autophagy of osteoblasts,but autophagy-related proteins participate in osteoblast differentiation and bone formation.Lack of autophagy in osteoblasts reduces mineralization and leads to an imbalance in the number of osteoblasts and osteoclasts,which results in bone loss and decreased bone density.The composite scaffold loaded with naringin can be used as a necessary carrier for bone defect repair and has excellent bone repair properties.Naringin can also accelerate the growth of new bone tissue by increasing the local contents of bone morphogenetic protein 2 and vascular endothelial growth factor.Naringin can regulate bone metabolism and inhibit oxidative stress via ERK,PI3K/Akt and Wnt signaling pathways to improve osteoporosis,which can play a good role in preventing and controlling the disease.However,the depth and breadth of the relevant research is insufficient.Based on the mechanism of the current study,we should investigate the specific mechanisms by which naringin regulates different pathways and inter-pathway interactions in the future,which will be beneficial to the multifaceted development of naringin used in the treatment of osteoporosis..

Objective:To prepare rabbit polyclonal antibodies against respiratory syncytial virus (RSV) N protein and use them as the detection antibodies to establish a N-ELISA-based method for rapid detection of neutralizing antibodies.Methods:A plasmid of pET30a-N for the expression of RSV N protein was constructed. After purification, the protein was immunized into New Zealand rabbits to prepare polyclonal antibodies, which were used as the detection antibodies. Positive serum samples were diluted and used to neutralize RSV (100 TCID 50/well). Hep-2 cells were inoculated and cultured, and then the cells were fixed with 80% acetone. ELISA was performed to detect RSV N protein in infected cells. When the absorbance value of a well was below the cut-off value, it was regarded as the positive well in the neutralization test. The highest dilution of a positive well serum was the neutralizing antibody titer. After optimizting the antibody dilution, detection time, cell density and the duration of neutralization, the method for neutralizing antibody detection was established based on N-ELISA. The established method was verified by analyzing the influences of different cell generations and edge effects, and calculating the accuracy, repeatability and precision. The correlation between the established method and microneutralization method was analyzed by detecting human RSV IgG-positive serum. Results:The plasmid pET30a-N was successfully constructed, and the expressed N protein showed high purity and good specificity. After the third immunization, the antibody titer in rabbit serum was 1∶51 200, and the antibodies could specifically bind to RSV. The prepared rabbit anti-RSV N polyclonal antibodies had a titer of 1∶51 200, and showed good specificity. The neutralizing antibodies could be detected on day 4 with the established method, and the duration of neutralization was shortened to 30 min. Cell generations and the position of wells in the 96-well plate (edge well and non-edge well) had no significant effect on the method, and the repeatability, precision and accuracy of the method were good. In the detection of 64 RSV IgG-positive human serum samples by the established method and microneutralization method, the correlation coefficient was 0.929 6, indicating a good positive correlation between the two methods.Conclusions:A N-ELISA-based method for rapid neutralizing antibody detection is successfully established, which can be used to evaluate the serum antibody level after RSV vaccination.

Objective:To explore whether barium chloride (BaCl 2) preconditioning has the protective effect on lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) model in mice and the possible mechanism. Methods:Sixty 8-12 week old healthy C57BL/6 male mice were randomly divided into control group, ARDS model group and BaCl 2 pretreatment group, with 20 mice in each group. The BaCl 2 pretreatment group was continuously injected with BaCl 2 (4 mg/kg through the tail vein) for 3 days before ARDS model establishment. ARDS model was established by intratracheally injecting (3 mg/kg) LPS. The control group was intratracheally given the same volume of 0.9% normal saline. On 24th hour after ARDS model establishment, some mice were sacrificed for obtaining fresh lung tissue. And the right lower lobe of the lung was separated for observing the pathological changes of lung tissue while the left lung tissue was used to measure the wet/dry weight ratio (W/D) of the lung. Some mice were sacrificed for observing pulmonary microvascular permeability at 2nd hours after injecting Evans blue (EB) through tail vein. The left mice were killed for alveolar lavage to measure the levels of tumor necrosis factor-α (TNF-α) via enzyme linked immunosorbent assay (ELISA). Results:Comparing with the control group, ARDS model group showed typical ARDS pathological changes, which included the increased W/D ratio (4.951±0.161 vs. 3.449±0.299, P < 0.01) and the content of EB in the lung tissue (μg/g: 0.130±0.027 vs. 0.085±0.011, P < 0.01), the damaged alveolar wall structure, lung congestion and exudates in the alveoli, as well as amounts of inflammatory cells. The pathological score of lung injury (10.33±1.15 vs. 1.67±0.58) and the level of TNF-α in BALF (ng/L: 900.85±247.80 vs. 68.21±5.79) were significantly increased in the ARDS model group (both P < 0.01). Comparing with the ARDS model group, the lung W/D ratio (4.620±0.125 vs. 4.951±0.161) and the EB content in the lung tissue (μg/g: 0.108±0.011 vs. 0.130±0.027) of BaCl 2 pretreatment group were significantly reduced (both P < 0.01). And the damaged pulmonary structural BaCl 2 pretreatment group were significantly alleviated. In addition, the pulmonary pathological score (5.00±1.00 vs. 10.33±1.15) and the level of TNF-α in BALF (ng/L: 169.16±73.33 vs. 900.85±247.80) were significantly decreased (both P < 0.01). Conclusion:Barium chloride pretreatment can improve the lung histopathological changes of ARDS model mice induced by LPS by reducing the permeability of pulmonary capillaries and local inflammatory reaction.Barium chloride has the protective effect against LPS attack in mice model of ARDS.

Objective:To observe the correlation between the frontal P-wave axis and the severity of chronic obstructive pulmonary disease (COPD) and the prognosis evaluation system.Methods:Patients with COPD>45 years old who were followed up in the outpatient department of Hunan Chest Hospital from January to July 2022 were continuously selected as subjects. At the same time, the healthy people who examined in the health management center of our hospital were in the control group. Both groups of subjects completed electrocardiogram and pulmonary function tests. The level of frontal P-wave axis and the results of pulmonary function examination were recorded, and the differences of frontal P-wave axis between the COPD group and the control group were compared, so as to clarify the value of frontal P-wave axis in the diagnosis, disease severity and prognosis evaluation of COPD.Results:The level of forced expiratory volume in the first second/forced vital capacity(FEV1/FVC )in the COPD group was significantly lower than that in the control group, while the level of P-wave axis was significantly higher than that in the control group (all P<0.05). The receiver operating characteristic (ROC) curve of P-wave axis showed that the AUC of P-wave axis in predicting COPD was 0.96 ( P<0.001), the best cut-off value was 63.80, the sensitivity was 0.89, and the specificity was 0.93. There were significant difference in P-wave axis level, the forced expiratory volume in one second to forced vital capacity ratio (FEV 1%pred), body mass index (BMI) and BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index between groups according to the degree of airflow limitation (all P<0.05). Correlation analysis showed that P-wave axis level was positively correlated with BODE index ( r=0.77, P<0.001), and negatively correlated with pulmonary function FEV 1%pred ( r=-0.76, P<0.001). Conclusions:There is a good correlation between the level of frontal P-wave axis and the severity of COPD and the prognosis evaluation system, which has clinical application value.

Objectives:To investigate the clinical and genetic features of young Chinese patients with myeloproliferative neoplasms (MPN) .Methods:In this cross-sectional study, anonymous questionnaires were distributed to patients with MPN patients nationwide. The respondents were divided into 3 groups based on their age at diagnosis: young (≤40 years) , middle-aged (41-60 years) , and elderly (>60 years) . We compared the clinical and genetic characteristics of three groups of MPN patients.Results:1727 assessable questionnaires were collected. There were 453 (26.2%) young respondents with MPNs, including 274 with essential thrombocythemia (ET) , 80 with polycythemia vera (PV) , and 99 with myelofibrosis. Among the young group, 178 (39.3%) were male, and the median age was 31 (18-40) years. In comparison to middle-aged and elderly respondents, young respondents with MPN were more likely to present with a higher proportion of unmarried status (all P<0.001) , a higher education level (all P<0.001) , less comorbidity (ies) , fewer medications (all P<0.001) , and low-risk stratification (all P<0.001) . Younger respondents experienced headache (ET, P<0.001; PV, P=0.007; MF, P=0.001) at diagnosis, had splenomegaly at diagnosis (PV, P<0.001) , and survey (ET, P=0.052; PV, P=0.063) . Younger respondents had fewer thrombotic events at diagnosis (ET, P<0.001; PV, P=0.011) and during the survey (ET, P<0.001; PV, P=0.003) . JAK2 mutations were found in fewer young people (ET, P<0.001; PV, P<0.001; MF, P=0.013) ; however, CALR mutations were found in more young people (ET, P<0.001; MF, P=0.015) . Furthermore, mutations in non-driver genes (ET, P=0.042; PV, P=0.043; MF, P=0.004) and high-molecular risk mutations (ET, P=0.024; PV, P=0.023; MF, P=0.001) were found in fewer young respondents. Conclusion:Compared with middle-aged and elderly patients, young patients with MPN had unique clinical and genetic characteristics.

To evaluate the association between serum anti-tissue transglutaminase antibody (anti-tTG) titers and the severity of histological damage to the duodenal mucosa and to predict a possible anti-tTG cutoff value for diagnosing celiac disease (CD) and villous atrophy in the domestic population. Clinical and pathological data from 76 adult CD patients with positive anti-tTG titers and duodenal biopsy results who were treated at the People′s Hospital of Xinjiang Uygur Autonomous Region from July 2017 to January 2022 were retrospectively analyzed. The correlation between anti-tTG titers and the severity of duodenal mucosal damage was statistically assessed to predict the optimal anti-tTG titer cut-off value for diagnosing CD and villous atrophy. Of the 76 patients, 10 had underlying CD, and of the 66 patients with duodenal histopathology, four were Marsh Ⅰ, six were Marsh Ⅱ, and 56 were Marsh Ⅲa-c grade. In adults with CD, anti-tTG titers were shown to be associated with the severity of histological damage to the duodenal mucosa. When the anti-tTG level was ≥5 times the upper limit of normal (ULN), the sensitivity and specificity for diagnosing CD were 83.9% and 92.9%, respectively. When the anti-tTG titer was ≥8 times the ULN, the sensitivity and specificity for diagnosing villous atrophy were 67.9% and 90.0%, respectively. Anti-tTG levels had a strong predictive value for diagnosing CD in adults when titers exceeded 10 times the ULN. Thus, the anti-tTG cut-off value can be combined with clinical judgment to diagnose CD, limiting the use of invasive endoscopy.