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 analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB).Methods:This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children′s Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children′s Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher′s exact test.Results:Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P=0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs.40% (25/62), P=0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion:ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.

Objective:To evaluate the role of minimal residual disease (MRD) monitoring during early induction therapy for the treatment of childhood acute lymphoblastic leukemia (ALL).Methods:This was a multicenter retrospective cohort study. Clinical data of 1 164 ALL patients first diagnosed between October 2016 and June 2019 was collected from 16 hospitals in South China Children′s Leukemia Group. According to MRD assay on day 15 of early induction therapy, they were divided into MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group. According to MRD assay on day 33, they were divided into MRD<0.01% group, MRD 0.01%-<1.00% group and MRD≥1.00% group. Age, onset white blood cell count, central nervous system leukemia (CNSL), molecular genetic characteristics and other data were compared between groups. Kaplan-Meier method was used for survival analysis. Cox regression model was used to analyze prognostic factors.Results:Of the 1 164 enrolled patients, there were 692 males and 472 females. The age of diagnosis was 4.7 (0.5, 17.4) years. The white blood cell count at initial diagnosis was 10.7 (0.4, 1 409.0) ×10 9/L. Among all patients, 53 cases (4.6%) had CNSL. The follow-up time was 47.6 (0.5, 68.8) months. The 5-year overall survival (OS) and 5-year relapse-free survival (RFS) rates were (93.1±0.8) % and (90.3±1.1) %. On day 15 of early induction therapy, there were 466 cases in the MRD<0.10% group, 523 cases in the MRD 0.10%-<10.00% group and 175 cases in the MRD≥10.00% group. The 5-year OS rates of the MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group were (95.4±1.0) %, (93.3±1.1) %, (85.4±2.9) %, respectively, while the RFS rates were (93.2±1.6) %, (90.8±1.4) %, (78.9±4.3) %, respectively ( χ2=16.47, 21.06, both P<0.05). On day 33 of early induction therapy, there were 925 cases in the MRD <0.01% group, 164 cases in the MRD 0.01%-<1.00% group and 59 cases in the MRD≥1.00% group. The 5-year RFS rates in the MRD 0.01%-<1.00% group was lowest among three groups ((91.4±1.2) % vs. (84.5±3.2) % vs. (87.9±5.1) %). The difference between three groups is statistically significant ( χ2=9.11, P=0.010). Among ALL patients with MRD≥10.00% on day 15 of induction therapy, there were 80 cases in the MRD <0.01% group on day 33, 45 cases in the MRD 0.01%-<1.00% group on day 33 and 45 cases in the MRD≥1.00% group on day 33. The 5-year RFS rates of three groups were (83.9±6.0)%, (67.1±8.2)%, (83.3±6.9)% respectively ( χ2=6.90, P=0.032). Univariate analysis was performed in the MRD≥10.00% group on day 15 and the MRD 0.01%-<1.00% group on day 33.The 5-year RFS rate of children with CNSL was significantly lower than that without CNSL in the MRD≥10.00% group on day 15 ((50.0±20.4)% vs. (80.3±4.4)%, χ2=4.13, P=0.042). Patients with CNSL or MLL gene rearrangement in the MRD 0.01%-<1.00% group on day 33 had significant lower 5-year RFS rate compared to those without CNSL or MLL gene rearrangement ((50.0±25.0)% vs. (85.5±3.1)%, χ2=4.06, P=0.044;(58.3±18.6)% vs. (85.7±3.2)%, χ2=9.44, P=0.002). Multivariate analysis showed that age ( OR=0.58, 95% CI 0.35-0.97) and white blood cell count at first diagnosis ( OR=0.43, 95% CI 0.27-0.70) were independent risk factors for OS. The MRD level on day 15 ( OR=0.55,95% CI 0.31-0.97), ETV6-RUNX1 fusion gene ( OR=0.13,95% CI 0.03-0.54), MLL gene rearrangement ( OR=2.55,95% CI 1.18-5.53) and white blood cell count at initial diagnosis ( OR=0.52,95% CI 0.33-0.81) were independent prognostic factors for RFS. Conclusions:The higher the level of MRD in early induction therapy, the worse the OS. The MRD levels on day 15 is an independent prognostic factor for RFS.The MRD in early induction therapy guided accurate risk stratification and individualized treatment can improve the survival rate of pediatric ALL.

Objective:To investigate the effects of fluoride exposure on kidney injury in rats and the sirtuin 3 (SIRT3)-fork head protein O3a (FOXO3a)-tensin homolog induced putative kinase 1 (PINK1)/E3 ubiquitin ligase (PARKIN) pathway.Methods:Twenty-four 4-week-old SD rats (clean grade, body mass 100 - 150 g) were selected and divided into three groups according to the randomized numeric table: control group, low fluoride group, and high fluoride group, with eight rats in each group (half male and half female). The control group was given free access to tap water (fluoride ion concentration < 0.5 mg/L), while the low fluoride and high fluoride groups were given free access to tap water and sodium fluoride solutions with fluoride ion concentrations of 5.0 and 50.0 mg/L, respectively, for a period of 180 days. The formation of dental fluorosis in rats was observed and recorded, and the femur, urine and blood samples of rats were collected to measure bone fluoride, urinary fluoride, and blood fluoride levels, and to detect kidney function related indicators (serum uric acid, creatinine, and urea nitrogen contents). Morphological changes of renal tissues stained with hematoxylin-eosin (HE) were observed under a light microscope. Real-time fluorescence quantitative PCR (qRT-PCR) and Western blotting were used to detect the mRNA and protein expression levels of renal SIRT3, FOXO3a, PINK1, PARKIN, microtubule associated protein 1 light chain 3 (LC3), autophagy receptor protein (P62), respectively.Results:Seven and one rats in the low and high fluoride groups were found to haveⅠdegree dental fluorosis, while zero and seven rats were found to haveⅡdegree dental fluorosis. Compared with the control group, rats in the low and high fluoride groups had higher levels of bone fluoride (μg/g: 1.18 ± 0.06, 2.16 ± 0.07 vs 0.52 ± 0.05), urinary fluoride (mg/L: 4.43 ± 0.11, 7.46 ± 0.09 vs 2.58 ± 0.14), blood fluoride (μg/ml: 0.77 ± 0.06, 1.68 ± 0.10 vs 0.52 ± 0.08), serum uric acid (μg/ml: 61.01 ± 4.17, 103.92 ± 5.43 vs 28.68 ± 2.91), creatinine (μg/ml: 74.82 ± 9.61, 132.05 ± 5.35 vs 22.38 ± 4.11), and urea nitrogen (μg/ml: 13.36 ± 1.27, 14.55 ± 0.34 vs 0.29 ± 0.07, P < 0.05). Under the light microscope, the kidneys of the control group showed tight and orderly arrangement of renal tubules and glomerular cells, with complete and clear cell contours. The low fluoride group was similar to the control group and no significant abnormalities were observed. The high fluoride group showed abnormal glomerular structure and atrophy, with some areas of renal tubules showing epithelial cell edema and unclear intercellular boundaries. The results of qRT-PCR assay showed that compared with the control group, the low and high fluoride groups had lower mRNA expression levels of SIRT3 (0.82 ± 0.03, 0.58 ± 0.02 vs 1.00 ± 0.08), P62 (0.75 ± 0.07, 0.28 ± 0.09 vs 1.00 ± 0.07, P < 0.05), and higher mRNA expression levels of FOXO3a (1.35 ± 0.04, 3.01 ± 0.23 vs 1.00 ± 0.08), PINK1 (1.58 ± 0.09, 3.28 ± 0.09 vs 1.00 ± 0.07), PARKIN (1.51 ± 0.04, 1.67 ± 0.10 vs 1.00 ± 0.05), LC3 (1.74 ± 0.07, 2.38 ± 0.18 vs 1.00 ± 0.08, P < 0.05). The results of Western blotting showed that compared with the control group, the low and high fluoride groups had lower protein expression levels of SIRT3 (0.91 ± 0.01, 0.55 ± 0.03 vs 1.00 ± 0.01), P62 (0.94 ± 0.27, 0.66 ± 0.38 vs 1.00 ± 0.19, P < 0.05), and higher protein expression levels of FOXO3a (1.14 ± 0.03, 1.22 ± 0.05 vs 1.00 ± 0.02), PINK1 (1.46 ± 0.03, 1.56 ± 0.03 vs 1.00 ± 0.05), PARKIN (1.98 ± 0.02, 2.33 ± 0.11 vs 1.00 ± 0.06), LC3 (4.10 ± 0.58, 4.93 ± 0.33 vs 1.00 ± 0.13, P < 0.05). Conclusion:Exposure to fluoride can cause renal tissue injury in rats, with downregulation of SIRT3 and P62 expression levels, and upregulation of FOXO3a, PINK1, PARKIN, and LC3 expression levels.

Objective:To learn about the infection and gene polymorphisms of hepatitis E virus (HEV) in murine-shaped animals of plague foci in Yunnan Province.Methods:From July to August 2019, around 16 natural villages (4 in Mile City, 6 in Mangshi and 6 in Lianghe County), which were the foci of domestic plague in Yunnan Province, the murine-shaped animals were captured by the night-time method. The liver RNA was extracted, and the target gene of rat HEV was detected by one-step real-time fluorescence quantitative PCR, and the positive rate of rat HEV was calculated. The rat HEV positive samples were amplified by PCR for further clone sequencing, and the resulting sequences were compared with the HEV sequences registered in the GenBank and a phylogenetic tree was constructed by using MegAlign and MEGA 7.0.Results:A total of 491 murine-shaped animals were captured from 3 orders, 5 families, 8 genera, 15 species, and the positive rate of rat HEV was 4.89% (24/491). Among them, the positive rate of Rattus tanezumi and Niviventer fulvescens was 9.39% (23/245) and 1/3, respectively; and other species were negative. There was a statistically significant difference in the positive rate of rat HEV between different habitats ( P = 0.014), and the positive rate of rat HEV in the habitats near the dwellings was higher than that in other habitats ( P < 0.05). The sequence comparison analysis showed that the gene sequence of P018 from Lianghe County was 100.0% homologous to the MG813927.1 sequence of the first patient with rat HEV in Hongkong, and it was clustered into the same branch with the sequences of MG813927.1 and LC549185.1 from rat, was the type HEV C. G024 from Mangshi shared a low homology (20.7% - 31.5%) with other virus strains, and it was clustered into the same branch with a HEV sequence from an avian (AY535004.1). Conclusions:Rat HEV is prevalent in murine-shaped animals of plague foci of Yunnan Province, and there may be gene polymorphisms of rat HEV. In addition, the difference infection rate may be related to the habitats.

Objective:To investigate the infection of spotted fever group Rickettsiae (SFGR) and Rickettsia mooseri ( R.mooseri) of wild rodents in the field of plague foci in Western Yunnan. Methods:The DNA of liver samples of 2 512 wild rodents captured from the plague foci in Lianghe County, Jianchuan County and Yulong County in Western Yunnan from 2015 to 2016 was extracted by magnetic bead method, and the heat shock protein groEL gene primers were used for nested PCR amplification. Gene sequence splicing and Blast homology comparison were performed using DNAStar 7.1 software and GenBank of the National Center for Biotechnology Information (NCBI) of the United States, respectively, and DNAStar 7.1 and MEGA 6.0 softwares were used to construct phylogenetic trees.Results:The wild rodents infected with SFGR were Mus pahari, Rattus steini, Crocidura attenuata and Suncus murinus (one for each), with a total infection rate of 0.16% (4/2 512); no R.mooseri infection was detected. The SFGR infection rates of wild rodents in the plague foci of Lianghe County and Jianchuan County were 0.49% (3/611) and 0.10% (1/1 029), respectively; no SFGR infection was detected in the wild rodents in the plague foci of Yulong County. The homology analysis showed that the homology between SFGR positive samples and reference sequences was 95.45%-100.00%; some of the groEL gene sequences were highly similar among the four positive samples, and the homology was 89.60%-97.40%. Sequence evolution analysis showed that the sequences of three SFGR positive samples from the plague focus in Lianghe County were clustered in the same branch, and the homology reached 94.40%-97.40%; one positive sample sequence from the plague focus in Jianchuan County was clustered in one branch. Conclusion:SFGR infection rate of wild rodents in the field of plague foci in Western Yunnan is low, and no R.mooseri infection is found.

Objective:To detect and analyze the contents of eight metal elements in water samples of plague foci in Yunnan Province.Methods:During the period from December 2015 to November 2016, the plague foci of Yulong, Jianchuan and Lianghe were selected as sampling sites, water samples were collected in areas with rodent activities in the 4 seasons of spring, summer, autumn and winter. The contents of eight metal elements calcium (Ca), iron (Fe), zinc (Zn), chromium (Cr), plumbum (Pb), manganese (Mn), cadmium (Cd) and cuprum (Cu) in water samples were measured by flame atomic absorption spectrometry (FAAS), and the data [median (interquartile distance)] were statistically analyzed.Results:Twenty-six, 58 and 54 water samples were collected from Yulong, Jianchuan and Lianghe plague foci, respectively. The contents of metal elements of Pb and Cd in water samples of the three plague foci [Yulong: 0.19 (0.78) and 0.08 (0.07) mg/L; Jianchuan: 0.23 (0.56) and 0.03 (0.06) mg/L; Lianghe: 0.13 (0.61) and 0.09 (0.08) mg/L] were higher than that of "Environmental Quality Standards for Surface Water" (Pb: 0.10 mg/L, Cd: 0.01 mg/L). There were significant differences in the contents of Ca and Cd elements among the three regions ( P < 0.05), but there was no significant difference in the contents of the other 6 metal elements among the three regions ( P > 0.05). The content of Ca element was the highest in Yulong plague foci, and the lowest in Lianghe plague foci ( P < 0.017). In the Yulong plague foci, there was no statistically significant difference in the content of Fe element in different seasons ( P > 0.05), and the differences in the contents of the other 7 metal elements were statistically significant ( P < 0.05). There was no significant difference in the content of Cr element in Jianchuan plague foci in different seasons ( P > 0.05), and the differences in the content of the other 7 metal elements were statistically significant ( P < 0.05). There was no significant difference in the content of Ca element in Lianghe plague foci in different seasons ( P > 0.05), and the differences in the content of the other 7 metal elements were statistically significant ( P < 0.05). Conclusion:The metal element contents of Pb and Cd are relatively abundant in water samples from 3 plague foci of Yunnan Province, and the seasonal variation trend of metal element content in water samples of Yulong and Jianchuan plague foci is similar.

Objective: To learn the effects of Dendrobium officinale flowers on testivular tissue morphology and sperm quality in parent and offspring rats,so as to provide reference for safety evaluation of Dendrobium officinale flowers. Methods: The 40 SD rats was randomly divided into the low-,middle-,high-dose and the control group,given 2.0,4.0,6.4 and 0 g/kgbw Dendrobium officinale flowers,respectively. After three months,the body weight,mass and organ/body coefficients of testis and epididymis of parent （P） and offspring （F1,F2） rats were measured;the number,activity and deformity of sperms were observed under microscope;the changes of testis and epididymis were observed by hematoxylin eosin staining. Results: There were no significantly statistical differences in the body weight,mass and organ/body coefficients of testis and epididymis,sperm quantity,sperm motility rate among four groups of P、F1、F2 male rats （P>0.05）. There were no significantly statistical differences in sperm malformation rate between the high-dose group and the control group （P>0.05）. There was no significant change in testis and epididymis of P,F1 and F2 male rats. Conclusion Dendrobium officinale flowers did not show obviously adverse effects on testivular tissue morphology and sperm quality in parent and offsping rats.

Objective: To learn the toxicity of Dendrobium officinale flowers to pregnant rats ( P, F1 ) and offspring rats ( F1, F2 ) before birth, so as to provide toxicological evidence for the safety assessment. Methods : The rats were divided into four groups with 20 female rats and 10 male each. The rats in three dose groups were fed with Dendrobium officinale flowers at the dose of 2.0, 4.0, 6.4g/kgbw. After two generation, the F1a and F2a rats were fed with basal diet; F1b and F2b rats were fed with Dendrobium officinale flowers. The body weights and total weight gains during the gestation, the conception rates, the pregnancy rates, the birth weights and survival rates of offspring rats were examined. Results: There were no statistically significant differences in the body weights and total weight gains during the gestation, the conception rates, and the pregnancy rates in pregnant rats ( P, F1 ) among the four groups ( P>0.05 ). There were also no statistically significant differences in the survival rates and live birth rates in offspring rats (F1, F2) between the dose groups and the control group ( P>0.05 ). Conclusions Dendrobium officinale flowers did not show obviously adverse effects on pregnant rats ( P, F1 ) and offspring rats ( F1, F2 ) before birth.

Objective To study the association between blood glucose control and mild cognitive impairment (MCI) in patients with diabetes mellitus and small-artery occlusion (SAO).Methods A screening study of cognitive impairment was conducted in the 676 patients diagnosed with SAO who had been treated at Department of Neurology,Huanhu Hospital from January 2010 through June 2017.They were divided into a normal cognition group (n=629) and an MCI group (n=47) according to the screening results.They were also divided into 4 groups according to their history of diabetes and levels of hemoglobin Alc:normal blood glucose group (n=398),stringent goals group (n=59),general goals group (n=46) and goals-not-met group (n=173).The differences were compared in terms of Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment Scale (MoCA) scores between the normal blood glucose,stringent goals,general goals and goals-not-met groups.We also analyzed the general clinical data and risk factors between the normal cognition and MCI groups.Variables of confounders that were identified as significant were entered into logistic regression.Results There were significant differences in MMSE and MoCA scores between the 4 groups (P＜0.05).Between the normal cognition and MCI groups,significant differences were found in proportion of smokers,blood glucose level and severity of stroke (P＜0.05).Logistic regression analysis showed that compared with the normal blood glucose group the incidence of MCI was 2.707-fold higher in the stringent goals group (OR=2.707,95％ CI:1.035～7.083,P=0.042),2.963-fold higher in the general goals group (OR=2.963,95％ CI:1.064～8.277,P=0.038) and 2.604-fold higher in the goals-not-met group (OR=2.604,95％ CI:1.269～5.341,P=0.009).Conclusions MCI is more likely to occur in acute phase in patients with diabetes and SAO stroke.The patients can benefit from joint managements of diabetes,stroke and cognitive dysfunction in clinical practice.