PKM2 Nuclear Translocation Promotes Glial Cell Activation and Aggravates the Brain Injury of Intracerebral Hemorrhage.

BACKGROUND: The purpose of this study was to investigate the potential involvement of pyruvate kinase M2 (PKM2), an enzyme acting as a rate-limiting enzyme in the final phase of glycolysis, in the regulation of glial activation and brain damage of intracerebral hemorrhage (ICH). METHODS: Western blotting and immunofluorescence were performed to investigate PKM2 expression, terminal deoxynucleotidyl transferase deoxyurinary triphosphate (dUTP) nick end labeling staining, hematoxylin and eosin staining, and behavioral tests were employed to evaluate the brain damage of ICH mice, and RNA-seq and bioinformatic analyses were performed to detect gene expression changes in ICH mice treated with TEPP-46. RESULTS: Increased PKM2 levels in perihematomal brain tissue were found starting from 3 days following ICH and peaked at 5 and 7 days post ICH. The increased expression of PKM2 was mainly co-localized with glial fibrillary acidic protein (GFAP)+ astrocytes and ionized calcium binding adaptor molecule-1 (IBA-1)+ microglia. Furthermore, we observed a notable increase in the nuclear translocation of PKM2 in glial cells following ICH. TEPP-46 treatment significantly reduced PKM2 nuclear translocation, and effectively attenuated glial activation and brain injury, and improved functional recovery of mice with ICH. RNA-seq data indicated that 91.1% (205/225) of differentially expressed genes (DEGs) were down-regulated in the TEPP-46 treated groups compared with the vehicle-treated groups in ICH brains. Furthermore, bioinformatic analyses revealed that these down-regulated DEGs were involved in a variety of biological processes, including autophagy and metabolic processes. In addition, the majority of these downregulated DEGs had a primary high expression in neurons, with subsequent expression seen in endothelial cells, microglia, and astrocytes. CONCLUSIONS: These results indicate that increased PKM2 nuclear translocation promotes the activation of glial cells after ICH, hence aggravating ICH-induced brain damage, and aggravates the brain injury induced by ICH. This highlights a potential therapeutic target for inhibiting glial activation to attenuate brain injury after ICH.

[Ecological Environment Assessment and Driving Mechanism Analysis of Nagqu and Amdo Sections of Qinghai-Xizang Highway Based on Improved Remote Sensing Ecological Index].

The ecological environment along the Qinghai-Xizang highway is an important part of the construction of the ecological civilization in the Xizang region, and current research generally suffers from difficulties in data acquisition, low timeliness, and failure to consider the unique "alpine saline" environmental conditions in the study area due to the unique geographical environment of the Qinghai-Xizang plateau. Based on the GEE platform and the unique geographical environment of the study area, the remote sensing ecological index (RSEI) was improved, and a new saline remote sensing ecological index (SRSEI) applicable to the alpine saline region was constructed by using principal component analysis as an ecological environment quality evaluation index. The spatial distribution pattern and temporal variation trend of ecological environment quality along the Qinghai-Xizang Highway Nagqu-Amdo section were analyzed at multiple spatial and temporal scales using the ArcGIS 10.3 platform and geographic probes, and the driving mechanisms of eight control factors, including natural and human-made, on the spatial and temporal changes in SRSEI were investigated. The results showed that:① compared with RSEI, SRSEI was more sensitive to vegetation and had a stronger discriminatory ability in areas with sparse vegetation and severe salinization, which is suitable for ecological quality evaluation in alpine saline areas. ② The spatial scale of ecological environment quality in the study area had obvious geographical differentiation, and the areas with poor ecological quality were mainly concentrated in the northern Amdo County, whereas the areas with excellent and good quality grades were mainly distributed in the central-western and southeastern Nagqu areas. On the temporal scale, the ecological environment of the study area as a whole showed an improvement trend over 32 years, and the vegetation cover in the central-western and southeastern areas increased significantly, which had a strong improvement effect on the ecological environment. The improvement area was 1 425.98 km2, accounting for 99.82%. The mean value of SRSEI was 0.49, with an overall fluctuating upward trend and an average increase of 0.015 7 a-1. ③ The land use pattern was the most driving influence factor in the change of ecological environment quality in the study area, with an average q value of 0.157 6 over multiple years, and the influence of environmental factors was low. The multi-factor interaction results showed that the ecological environment in the study area was the result of multiple factors acting together, all factors had synergistic enhancement under the interaction, the influence of human factors was gradually increasing, and the interaction of the net primary productivity (NPP) of vegetation and land use pattern was the main interactive control factor of ecological environment quality in the study area. This study can provide a theoretical basis for ecological environmental protection and sustainable development along the Nagqu to Amdo section.

[Seasonal variation of water utilization sources and responses to precipitation in the dominant species of broad-leaved and needle-leaved mixed forests in Mount Lushan, China]. / 庐山针阔混交林优势种水分利用来源季节变化及对降水的响应.

Elucidating the seasonal patterns of water sources for dominant species in the sub-tropical humid mountainous forest, analyzing the eco-hydrological complementarity and competition mechanisms among coexisting species, investigating the responses of plant water utilization to precipitation, could provide a theoretical basis for vegetation restoration and management. Based on the stable hydrogen and oxygen isotope technique, we analyzed the δ2H and δ18O characteristics of precipitation, xylem water from Pinus massoniana and Quercus variabilis, and soil water from 0-100 cm depth in Mount Lushan, China. The MixSIAR model, Levins index, and PS index were used to calculate the relative contribution rate of each water source, the hydrological niche breadth, and niche overlap of P. massoniana and Q. variabilis. The results showed that, in the wet season (March to July), P. massoniana primarily utilized soil water from the 0-20 cm and 20-40 cm depths, while Q. variabilis primarily utilized that from the 20-40 cm and 40-60 cm depths. During the dry season (August to September), P. massoniana and Q. variabilis utilized 40-60 cm and 60-80 cm of soil water, respectively, resulting in an increase in the depth of water absorption. In the early growing season (March to April) and the late growing season (September), there was a high hydrological niche overlap between P. massoniana and Q. variabilis, resulting in intensitive water competition. In the middle of the growing season (May to August), the water source was adequately allocated, and the hydrolo-gical niche was segregated to meet the high transpiration demand. Q. variabilis primarily utilized soil water from a depth of 60-80 cm and 60-80 cm before a precipitation event, and from a depth of 0-20 cm and 20-40 cm after the event. In contrast, P. massoniana primarily utilized soil water from a depth of 0-20 cm and 20-40 cm both before and after a precipitation event. In conclusion, water utilization patterns of P. massoniana and Q. variabilis exhibited a seasonal trend, with shallow water uptake during the rainy season and deep water uptake during the dry season. These species are capable of efficiently allocating water resources during the peak growth season, and their root systems actively respond to change in soil moisture level. They have strong adaptability to extreme precipitation events and exhibit remarkable water conservation capabilities.

The effect of self-designed metabolic equivalent exercises on cancer-related fatigue in patients with gastric cancer: A randomized controlled trial.

AIMS: To investigate the effect of Self-designed Metabolic Equivalent Exercises (SMEE) on cancer-related fatigue in patients with gastric cancer. METHODS: 130 patients with gastric cancer admitted to Department of Oncology of a tertiary hospital in Shanghai were enrolled and assessed for eligibility. After excluding 1 patient who declined to participate, 129 eligible patients were randomly assigned into SMEE (n = 65) and control (n = 64) groups. The Revised Piper Fatigue Scale (RPFS) and EORTC QLQ-C30 Quality of Life Scale were used to measure cancer-caused fatigue and quality of life, respectively, in both groups at the first admission and after 3 months. RESULTS: After excluding patients who did not receive allocated intervention due to medical (n = 3) and personal (n = 2) reasons, those who were lost to follow-up (n = 3), and those who had discontinued intervention (n = 2), 119 patients (64 in the SMEE group and 55 in the control group) were included for analysis. There were no statistically significant differences in the RPFS or QLQ-C30 score between the two groups at baseline. After 3 months, the total RPFS score of the SMEE group was significantly lower than that of the control group (2.86 ± 1.75 vs. 4.65 ± 1.29, p = 0.009), with significant improvements in affective meaning (0.83 ± 0.92 vs. 1.13 ± 0.77, p = 0.044) and sensory (0.70 ± 0.71 vs. 1.00 ± 0.54, p < 0.001) subscales; in the SMEE group, QLQ-C30 scores in somatic (2.00 ± 0.27 vs. 1.31 ± 0.26, p < 0.001), emotional (2.67 ± 0.58 vs. 2.07 ± 0.48, p < 0.001), and social (3.23 ± 0.58 vs. 1.64 ± 0.51, p < 0.001) functioning were significantly higher than those in the control group, with significant improvements in fatigue (p < 0.001), nausea/vomiting (p = 0.014), shortness of breath (p < 0.001), constipation (p < 0.001), and diarrhea (p = 0.001) dimensions. CONCLUSION: The self-programmed metabolic equivalent manipulation as an exercise intervention could effectively reduce the degree of cancer-caused fatigue and improve quality of life in patients with gastric cancer.

Astrocyte-derived lactate aggravates brain injury of ischemic stroke in mice by promoting the formation of protein lactylation.

Aim: Although lactate supplementation at the reperfusion stage of ischemic stroke has been shown to offer neuroprotection, whether the role of accumulated lactate at the ischemia phase is neuroprotection or not remains largely unknown. Thus, in this study, we aimed to investigate the roles and mechanisms of accumulated brain lactate at the ischemia stage in regulating brain injury of ischemic stroke. Methods and Results: Pharmacological inhibition of lactate production by either inhibiting LDHA or glycolysis markedly attenuated the mouse brain injury of ischemic stroke. In contrast, additional lactate supplement further aggravates brain injury, which may be closely related to the induction of neuronal death and A1 astrocytes. The contributing roles of increased lactate at the ischemic stage may be related to the promotive formation of protein lysine lactylation (Kla), while the post-treatment of lactate at the reperfusion stage did not influence the brain protein Kla levels with neuroprotection. Increased protein Kla levels were found mainly in neurons by the HPLC-MS/MS analysis and immunofluorescent staining. Then, pharmacological inhibition of lactate production or blocking the lactate shuttle to neurons showed markedly decreased protein Kla levels in the ischemic brains. Additionally, Ldha specific knockout in astrocytes (Aldh1l1 CreERT2; Ldha fl/fl mice, cKO) mice with MCAO were constructed and the results showed that the protein Kla level was decreased accompanied by a decrease in the volume of cerebral infarction in cKO mice compared to the control groups. Furthermore, blocking the protein Kla formation by inhibiting the writer p300 with its antagonist A-485 significantly alleviates neuronal death and glial activation of cerebral ischemia with a reduction in the protein Kla level, resulting in extending reperfusion window and improving functional recovery for ischemic stroke. Conclusion: Collectively, increased brain lactate derived from astrocytes aggravates ischemic brain injury by promoting the protein Kla formation, suggesting that inhibiting lactate production or the formation of protein Kla at the ischemia stage presents new therapeutic targets for the treatment of ischemic stroke.

Extent of lymphadenectomy for esophageal cancer / 中华胃肠外科杂志

Esophageal cancer is a common malignant tumor in China. For resectable ones, surgery is still the primary treatment. At present, the extent of lymph node dissection remains controversial. Extended lymphadenectomy makes metastatic lymph nodes more likely to be resected, which contributed to pathological staging and postoperative treatment. However,it may also increase the risk of postoperative complications and affect prognosis. Therefore, it is controversial how to balance the optimal extent/number of dissected lymph nodes for radical resection with the lower risk of severe complications. In addition, whether the lymph node dissection strategy should be modified after neoadjuvant therapy needs to be investigated, especially for patients who have a complete response to neoadjuvant therapy. Herein, we summarize the clinical experience on the extent of lymph node dissection in China and worldwide, aiming to provide guidence for the extent of lymph node dissection in esophageal cancer.

Blood metabolites in preterm infants with retinopathy of prematurity based on tandem mass spectrometry: a preliminary study / 中国当代儿科杂志

OBJECTIVES@#To study new biomarkers for the early diagnosis of retinopathy of prematurity (ROP) by analyzing the differences in blood metabolites based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and metabolomics.@*METHODS@#Dried blood spots were collected from 21 infants with ROP (ROP group) and 21 infants without ROP (non-ROP group) who were hospitalized in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2013 to December 2016. LC-MS/MS was used to measure the metabolites, and orthogonal partial least squares-discriminant analysis was used to search for differentially expressed metabolites and biomarkers.@*RESULTS@#There was a significant difference in blood metabolic profiles between the ROP and non-ROP groups. The pattern recognition analysis, Score-plot, and weight analysis obtained 10 amino acids with a relatively large difference. Further statistical analysis showed that the ROP group had significant increases in blood levels of glutamic acid, leucine, aspartic acid, ornithine, and glycine compared with the non-ROP group (P<0.05). The receiver operating characteristic curve analysis showed that glutamic acid and ornithine had the highest value in diagnosing ROP.@*CONCLUSIONS@#Blood metabolites in preterm infants with ROP are different from those without ROP. Glutamic acid and ornithine are the metabolic markers for diagnosing ROP. LC-MS/MS combined with metabolomics analysis has a potential application value in the early identification and diagnosis of ROP.

Efficacy analysis of anlotinib combined with chemotherapy for advanced non-small cell lung cancer after failure of second-line chemotherapy / 国际肿瘤学杂志

Objective:To observe the efficacy and safety of anlotinib combined with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) who failed second-line chemotherapy.Methods:A retrospective analysis was performed on 80 patients with advanced NSCLC who had failed second-line chemotherapy admitted in the Department of Oncology of Chaohu Hospital of Anhui Medical University from January 2017 to October 2019, and the patients were divided into control group ( n=36) and observation group ( n=44) according to the different treatment regimens. The control group was given pemetrexed + cisplatin, and the observation group adopted pemetrexed + cisplatin + anlotinib. The objective response rate (ORR), disease control rate (DCR), median progression-free survival (PFS), overall survival (OS), changes in levels of serum vascular endothelial growth factor (VEGF), carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) and treatment-related adverse reactions were compared between the two groups. Results:After 2 cycles of treatment, the ORR in the control group and observation group were 5.56% (2/36) and 18.18% (8/44), with no statistically significant difference ( χ2=1.85, P=0.174). The DCR in the two groups were 58.33% (21/36) and 81.82% (36/44), and the DCR in the observation group was significantly higher than that in the control group, with a statistically significant difference ( χ2=5.33, P=0.021). The median PFS in the two groups were 4.0 months and 6.0 months, and the median PFS in the observation group was longer than that in the control group, with a statistically significant difference ( χ2=28.47, P<0.001). The median OS in the two groups were 13.0 months and 14.8 months, with no statistically significant difference ( χ2=1.56, P=0.212). The levels of serum VEGF [(21.72±5.42) ng/L vs. (36.97±7.53) ng/L, t=14.13, P<0.001; (16.61±4.14) ng/L vs. (38.85±8.61) ng/L, t=23.09, P<0.001], CEA [(4.91±1.58) ng/ml vs. (6.62±2.84) ng/ml, t=4.64, P<0.001; (3.07±1.32) ng/ml vs. (7.08±3.31) ng/ml, t=11.50, P<0.001] and CA199 [(16.83±5.23) U/ml vs. (20.95±7.94) U/ml, t=3.75, P<0.001; (13.37±5.85) U/ml vs. (21.66±8.72) U/ml, t=7.55, P<0.001] in the control group and observation group after 2 cycles of treatment were significantly decreased compared with those before treatment, and the levels of serum VEGF, CEA and CA199 in the observation group were significantly lower than those in the control group ( t=4.78, P<0.001; t=5.68, P<0.001; t=2.76, P=0.007). The incidence of elevated blood pressure in the observation group was significantly higher than that in the control group [25.00% (11/44) vs. 2.78% (1/36), χ2=7.67, P=0.006]. Conclusion:Pemetrexed + cisplatin + anlotinib regimen for patients with advanced NSCLC who failed second-line chemotherapy can improve DCR, prolong PFS and improve the levels of serum tumor-related markers, with controllable adverse reactions.

Current status of minimally invasive techniques in the field of esophageal surgery / 中华消化外科杂志

Esophageal cancer is a common malignant tumor of the digestive system in China. Currently, surgical resection is the main treatment for localized and resectable esophageal cancer. Minimally invasive treatment of esophageal cancer has the advantages of small trauma, neat incision, less pain, quick postoperative recovery, low postoperative complication incidence and mortality, and the treatment effect is comparable to traditional open surgery. Therefore, minimally invasive surgery for esophageal cancer has gradually become the mainstream choice for esophageal surgery. Various minimally invasive treatment approaches for esophageal cancer have correspon-dingly different indications, advantages and disadvantages. With the continuous development of minimally invasive technology, the shortcomings of various minimally invasive surgical approaches have been continuously overcome, which has brought about the diversification of minimally invasive treatment options. The authors comb the latest research progress at home and abroad, discuss and summarize the current application of minimally invasive techniques in esophageal surgery, hoping to provide references for the clinical minimally invasive treatment of esophageal cancer.

Clinical diagnosis of Potocki-Shaffer syndrome and literature review / 中华实用儿科临床杂志

Objective:To summarize the clinical and genetic characteristics of Potocki-Shaffer syndrome (PSS).Methods:A retrospective study was conducted to analyze the clinical data of 1 patient diagnosed with PSS in the Department of Pediatrics of the Sixth Affiliated Hospital, Sun Yat-Sen University at February 2021.The data analyzed included clinical manifestations, biochemical tests and gene tests.Meanwhile, studies were retrieved from the China National Knowledge Internet database, Wanfang database, and PubMed database from the establishment of the database to December 2021 by taking " Potocki-Shaffer syndrome" " EXT2 gene" " AlX4 gene" and " PHF21A gene" as key words.Besides, genes were searched from the Online Frontal Analysis Mendelian Inheritance in Man.The clinical and genetic features of PSS patients were summarized. Results:The patient was 5 months and 21 days old, male, who was admitted to the hospital due to excessive growth in body mass for the past 3 months.The patient showed mental and motor retardation, overgrowth, concealed penis, hearing loss, and hypotonia.Whole exon sequencing of this patient revealed heterozygous deletions in the Chr11: 44069455-48188946 region, including the deletions of 3 autosomal dominant genes: EXT2, ALX4, and PHF21A.The patient was diagnosed with PSS.A total of 14 articles published in English were collected, involving this boy and other 35 patients.In these patients, 14 cases had point mutations, and 22 cases had large deletions. PHF21A gene variation was detected in 23 cases (dysgnosia in 22 cases, dyskinesia in 21 cases, language development delay in 18 cases). EXT2 gene variation was observed in 22 cases (exostoses in 13 cases). ALX4 gene variation was found in 19 cases (bilateral parietal foramina in 15 cases). Of 36 cases, 27 cases had craniofacial anomalies. Conclusions:The main clinical symptoms of PSS are language and motor developmental delay, intellectual disability, exostoses, bilateral parietal foramina, and craniofacial anomalies, which are closely related to 3 autosomal dominant genes ALX4, EXT2 and PHF21A.Genetic testing facilitates the clinical diagnosis of PSS, and the mutation types are dominated by point mutations and large deletions.

Genetic analysis in 331 cases of neonatal hyperbilirubinemia with unknown etiology / 中国新生儿科杂志

Objective:To study the genetic profile of neonatal hyperbilirubinemia with unknown etiology in Guangdong Province and the clinical significance of jaundice-related genetic screening.Methods:From July to September, 2021, neonates with hyperbilirubinemia of unknown etiology born in different hospitals in Guangdong Province were studied. 24 neonatal jaundice-related exons were sequenced using targeted capture and high-throughput sequencing technology. The pathogenic variants were analyzed.Results:A total of 331 cases, 139 (42.0%) cases showed positive screening results with five diseases, including 65 (19.6%) cases of Gilbert syndrome, 48 (14.5%) cases of glucose-6-phosphate dehydrogenase (G6PD) deficiency,18 (5.4%) cases of sodium taurocholate cotransporting polypeptide deficiency, 4 (1.2%) cases of Citrin deficiency and 4 (1.2%) cases of Dubin-Johnson syndrome. 149 (45.0%) cases carried one or more genetic variants and 43 (13.0%) cases showed no clinically significant variants. The 8 high-frequency mutation loci (carrier rate >1%) are UGT1A1 gene c.211G>A and c.1091C>T, G6PD gene c.1466G>T and c.1478G>A, SLC10A1 gene c.800C>T, SLC25A13 gene c.852_855del TATG, HBB gene c.126_129delCTTT and c.316-197C>T.Conclusions:Genetic factors are important for neonatal hyperbilirubinemia with unknown etiology in Guangdong. The common pathogenic genes are UGT1A1, G6PD, SLC10A1, and SLC25A13 and the population carries high-frequency mutation loci. Therefore, genetic screening in neonates with hyperbilirubinemia of unknown etiology has important clinical significance.

Molecular mechanism of Gegen Qinlian Decoction in promoting differentiation of brown adipose tissue to improve glucose and lipid metabolism disorders in diabetic rats / 中国中药杂志

This study explored the molecular mechanism underlying the Gegen Qinlian Decoction(GQD) promoting the differentiation of brown adipose tissue(BAT) to improve glucose and lipid metabolism disorders in diabetic rats. After the hypoglycemic effect of GQD on diabetic rats induced by high-fat diet combined with a low dose of streptozotocin was confirmed, the total RNA of rat BAT around scapula was extracted. Nuclear transcription genes Prdm16, Pparγc1α, Pparα, Pparγ and Sirt1, BAT marker genes Ucp1, Cidea and Dio2, energy expenditure gene Ampkα2 as well as BAT secretion factors Adpn, Fndc5, Angptl8, IL-6 and Rbp4 were detected by qPCR, then were analyzed by IPA software. Afterward, the total protein from rat BAT was extracted, and PRDM16, PGC1α, PPARγ, PPARα, SIRT1, ChREBP, AMPKα, UCP1, ADPN, NRG4, GLUT1 and GLUT4 were detected by Western blot. The mRNA expression levels of Pparγc1α, Pparα, Pparγ, Ucp1, Cidea, Ampkα2, Dio2, Fndc5, Rbp4 and Angptl8 were significantly increased(P<0.05) and those of Adpn and IL-6 were significantly decreased(P<0.05) in the GQD group compared with the diabetic group. In addition, Sirt1 showed a downward trend(P=0.104), whereas Prdm16 tended to be up-regulated(P=0.182) in the GQD group. IPA canonical pathway analysis and diseases-and-functions analysis suggested that GQD activated PPARα/RXRα and SIRT1 signaling pathways to promote the differentiation of BAT and reduce the excessive lipid accumulation. Moreover, the protein expression levels of PRDM16, PGC1α, PPARα, PPARγ, SIRT1, ChREBP, AMPKα, UCP1, GLUT1, GLUT4 and NRG4 were significantly decreased in the diabetic group(P<0.01), which were elevated after GQD intervention(P<0.05). Unexpectedly, the expression of ADPN protein in the diabetic group was up-regulated(P<0.01) as compared with the control group, which was down-regulated after the administration with GQD(P<0.01). This study indicated that GQD promoted BAT differentiation and maturity to increase energy consumption, which reduced the glucose and lipid metabolism disorders and thereby improved diabetes symptoms.

Road traffic injury mortality and morbidity by country development status, 2011-2017 / 中华创伤杂志(英文版)

PURPOSE@#This research examined road traffic injury mortality and morbidity disparities across of country development status, and discussed the possibility of reducing country disparities by various actions to accelerate the pace of achieving Sustainable Development Goals target 3.6 - to halve the number of global deaths and injuries from road traffic accidents by 2020.@*METHODS@#Data for road traffic mortality, morbidity, and socio-demographic index (SDI) were extracted by country from the estimates of the Global Burden of Disease study, and the implementation of the three types of national actions (legislation, prioritized vehicle safety standards, and trauma-related post-crash care service) were extracted from the Global Status Report on Road Safety by World Health Organization. We fitted joinpoint regression analysis to identify and quantify the significant rate changes from 2011 to 2017.@*RESULTS@#Age-adjusted road traffic mortality decreased substantially for all the five SDI categories from 2011 to 2017 (by 7.52%-16.08%). Age-adjusted road traffic mortality decreased significantly as SDI increased in the study time period, while age-adjusted morbidity generally increased as SDI increased. Subgroup analysis by road user yielded similar results, but with two major differences during the study period of 2011 to 2017: (1) pedestrians in the high SDI countries experienced the lowest mortality (1.68-1.90 per 100,000 population) and morbidity (110.45-112.72 per 100,000 population for incidence and 487.48-491.24 per 100,000 population for prevalence), and (2) motor vehicle occupants in the high SDI countries had the lowest mortality (4.07-4.50 per 100,000 population) but the highest morbidity (428.74-467.78 per 100,000 population for incidence and 1025.70-1116.60 per 100,000 population for prevalence). Implementation of the three types of national actions remained nearly unchanged in all five SDI categories from 2011 to 2017 and was consistently stronger in the higher SDI countries than in the lower SDI countries. Lower income nations comprise the heaviest burden of global road traffic injuries and deaths.@*CONCLUSION@#Global road traffic deaths would decrease substantially if the large mortality disparities across country development status were reduced through full implementation of proven national actions including legislation and law enforcement, prioritized vehicle safety standards and trauma-related post-crash care services.

Analysis of amino acid and acylcarnitine profile in full-term newborns small for gestational age / 中华实用儿科临床杂志

Objective:To compare the difference of blood amino acids and acylcarnitine levels between small-for-gestational-age (SGA) and appropriate-for-gestational age (AGA) full-term newborns, and to explore the changes of the blood metabolism spectrum of full-term SGA, so as to provide evidence for clinical intervention.Methods:Seventy-nine full-term SGA newborns born in the Sixth Affiliated Hospital of Sun Yat-Sen University from January to December 2018 were selected as the study objects.Seventy-nine gestational age-and gender-matched healthy full-term AGA newborns born in the same hospital at the same time were selected as the control group.The dry blood spot samples were collected and detected by tandem mass spectrometry on the third day after birth.The differences between two groups and considerable biomarkers were explored by the orthogonal partial least squares discriminant analysis (OPLS-DA).Results:The birth weight of SGA newborns was (2.5±0.2) kg, and that of AGA newborns was (3.2±0.3) kg.OPLS-DA model analysis showed that 12 kinds of blood metabolites were identified which possessed the biggest weight discriminating the full-term SGA group from the AGA group, and the ratios of these blood metabolites of two groups were compared as follows: propionylcarnitine (0.34±0.13 vs. 0.42±0.15), tyrosine [0.24(0.18, 0.27) vs.0.28(0.22, 0.37)], free carnitine (0.43±0.14 vs. 0.37±0.12), valine [0.39(0.35, 0.45) vs.0.44(0.36, 0.53)], octanoylcarnitine (0.33±0.13 vs. 0.29±0.09), myristoylcarnitine (0.35±0.12 vs. 0.31±0.10), butylcartine (0.37±0.13 vs. 0.41±0.14), 3-hydroxyisovlerylcartine[0.35(0.25, 0.43) vs.0.35(0.26, 0.45)], decenoylcarnitine (0.26±0.13 vs. 0.23±0.08), isovalerylcarnitine[0.33(0.26, 0.34) vs.0.33(0.30, 0.35)], leucine [0.38(0.30, 0.47) vs.0.40(0.33, 0.48)]and methionine (0.42±0.14 vs. 0.46±0.15). The level of propionylcarnitine ( t=3.920), tyrosine ( Z=3.536) and valine ( Z=2.838) in the full-term SGA group were significantly lower than those in the AGA group, while the levels of free carnitine ( t=-2.863), octanoylcarnitine ( t=-2.266) and myristoylcarnitine ( t=-2.194) in the full-term SGA group were significantly higher than those in the AGA group (all P<0.05). Conclusions:The concentration of amino acids and acylcarnitine in the blood of SGA newborns is different from that in AGA newborns.Aromatic amino acids and branched chain amino acids should be added in full-term SGA nutrition support as they can meet the energy metabolism by mobilizing medium and long chain fatty acids in the early stage.

Application of gene screening technology in screening common newborn genetic diseases / 中华实用儿科临床杂志

Objective:To detect the genes of common genetic diseases in newborns with the high-throughput sequencing technology based on target gene capture, to study the incidence rate of such diseases, the carrying rate and variant types of pathogenic mutations related to such diseases, and to explore the application value of the high-throughput sequencing technology in screening genetic diseases of newborns.Methods:The heel blood of 1 793 newborns born in Guangdong province from June 2019 to April 2020 were collected, and the exon regions of 138 common genetic disease-related genes in neonates were detected using the high-throughput sequencing technology based on target gene capture.The pathogenicity of the mutations was interpreted according to the " Classification Criteria and Guidelines for Genetic Variation(2017)" , in which known disease and probable disease were considered as positive mutations.The positive mutations were verified by Sanger sequencing technology, and the test results were analyzed with statistical methods.Results:Among the 1 793 newborns, 978 were male and 815 were female.A total of 158 positive cases were screened(8.81%), and 11 positive diseases were detected.Among the positive diseases, there were 41 cases(2.29%)of autosomal recessive deafness type 1A, 40 cases(2.23%)of Gilbert syndrome or Crigler-Najjar syndrome, and 33 cases(1.84%)of glucose-6-phosphate dehydrogenase deficiency(1.84%), 19 cases(1.06%)of familial hypercho-lesterolemia, 18 cases(1.00%) of sodium taurocholate cotransporter peptide deficiency disease, 2 cases(0.11%)of mitochondrial non-syndromic deafness, 2 cases(0.11%)of Citrin deficiency, 1 case(0.06%)of holocarboxylase synthase deficiency, 1 case(0.06%)of β-thalassemia and 1 case(0.06%)of metachromatic leukodystrophies.Of all studied cases, 972 carried one or more positive mutations, involving 85 kinds of diseases in total.The diseases with a high carrying rate were Gilbert syndrome or Crigler-Najjar syndrome(359 cases, 20.02%), autosomal recessive deafness type 1A(302 cases, 16.84%), and sodium taurocholate cotransport peptide deficiency disease(291 cases, 16.22%). The high-frequency mutation sites were UGT1A1 gene c. 211G> A, GJB2 gene c .109G> A and SLC10A1 gene c. 800C> T. Conclusions:The common genetic diseases detected in neonates from Guangdong province are autosomal recessive deafness type 1A, Gilbert syndrome or Crigler-Najjar syndrome, glucose-6-phosphate dehydrogenase deficiency, familial hypercholesterolemia, and sodium taurocholate cotransport peptide deficiency.There are high-frequency carrying mutation sites in the population.Preliminary genetic screening of common neonatal genetic diseases can accumulate data and experience for the development of newborn genetic screening.

A study on the association between vascular endothelial growth factor A polymorphisms and necrotizing enterocolitis / 中国新生儿科杂志

Objective To study the relationship between single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor A (VEGFA) gene and neonatal necrotizing enterocolitis (NEC).Method From August 2014 to December 2016,preterm infants with a ≥ Ⅱ stage (Modified Bell staging criteria) of NEC admitted to our hospitals were assigned as NEC group.Preterm infants without NEC with similar gestational age and body weight during the same period were assigned as the control group.SNPs of VEGFA including rs1005230,rs833067,rs3025010,rs3025035,rs3025036,rs10434,and rs6905288 were analyzed using SEQUENOM MassARRAY platform and multiplex allele-specific PCR.The concentration of VEGFA in the plasma of the two groups was examined using enzyme-linked immunosorbent assay (ELISA).Result A total of 110 infants were reviewed,including 30 infants in NEC group and 80 infants in the control group.The results showed a significant association of the minor allele frequency (MAF) for T in rs1005230 and C in rs833067 with NEC.The frequencies of C/T (OR=4.810,95％CI 1.742～13.278) and C/T-T/T (OR=4.892,95％CI 1.801～13.246) genotypes in rs1005230,and frequencies of T/C (OR=4.373,95％CI 1.578～12.129) and T/C-C/C (OR=4.000,95％CI 1.484～10.828) genotypes in rs833067 were significantly higher in NEC group than the control group (P＜0.05).Infants with MAF in rs1005230 and rs833067 had significantly lower plasma level of VEGFA than infants without MAF (P＜0.01).Conclusion The SNPs of rs1005230 and rs833067 may be associated with lower level of VEGFA in plasma and higher risk for NEC.

The Predictive value of umbilical cord blood regulatory T cells for bronchopulmonary dysplasia in preterm infants / 中国新生儿科杂志

Objective To study the predictive value of umbilical cord blood regulatory T cells (Treg) for bronchopulmonary dysplasia (BPD) in preterm infants. Method From June 2017 to December 2018, premature infants with gestational age less than 32 weeks admitted to NICU of our hospiatal were prospectively selected. The umbilical cord blood was collected at birth to examine the Treg amount. The infants were assigned into BPD group and non-BPD group according to the diagnosis at discharge. The differences of Treg amount between the two groups and different degrees of BPD were analysed. Result A total of 124 premature infants (GA<32 weeks) were admitted, including 41 cases in BPD group (mild, n=18;moderate, n=14; severe, n=9) and 83 cases in the non-BPD group. The BPD group had GA of (29.6 ± 1.1) weeks and birth weight (BW) of (1128 ± 135) g. The non-BPD group had GA of (29.8 ± 1.1) weeks and BW of (1316 ± 180) g. The birth weight, 1min and 5min Apgar scores in BPD group were lower than the non-BPD group (P<0.001). The BPD group had higher incidence of respiratory distress syndrome, longer duration of mechanical ventilation (MV) and oxygen inhalation(P<0.001) than the non-BPD group. The MV duration and oxygen inhalation duration in the severe BPD group were significantly longer than the moderate and mild BPD groups, and the duration in the moderate group was longer than the mild group (P<0.001). The number of Treg in cord blood in the BPD group [(1.43 ± 0.06) × 105 cells/ml] was significantly lower than the non-BPD group [(2.57 ± 0.09) × 105 cells/ml], and the difference was statistically significant (P<0.001). Multivariate Logistic regression analysis showed that a significant decrease in the number of Treg was a risk factor for BPD in premature infants (OR=0.000, 95％CI 0.000 ～ 0.012, P=0.009). The number of Treg in umbilical cord blood was negatively correlated with the severity of BPD. The area under the ROC curve showed that the cut-off value was 1.95 × 105 cells/ml, with Youden index 0.613, sensitivity 85.4％ and specificity 75.9％. Conclusion The number of cord blood Treg cells may be a useful biomarker for predicting BPD in premature infants.

Differential analysis of urinary metabolites of premature infants with bronchopulmonary dysplasia within 36 hours after birth / 中国新生儿科杂志

Objective To study the characteristics of urinary metabolites in the premature infants with or without bronchopulmonary dysplasia (BPD) within 36 hours after birth and to find new biomarkers for the early warning indicators for BPD.Method From January 2014 to October 2016,premature infants hospitalized in the Sixth Affiliated Hospital of Sun Yat-sen University with gestational age ＜ 32 weeks,hospitalization time ＞ 28 days and urine samples were collected within 36 hours after birth for metabolite detection were enrolled in the study.Preterm infants diagnosed as BPD were selected as the BPD group.Preterm infants with the same gestational age,days of age with the BPD group had no BPD were selected as the control group at a ratio of 1 ∶ 1.The gas chromatography-mass spectrometry was used to measure the metabolites.The data were analyzed using orthogonal partial least squares discriminant analysis and receiver operating characteristic (ROC) curve and the area under which were used to determine the performance of differential metabolites in the diagnosis of BPD.Result There were 20 patients in the BPD group and 20 patients in the control group.Within 36 hours after birth,in the BPD group,the level of fucose and tartrate in urine (nmol/mgCr) were significantly lower than that in the control group [0.00 (0.00,0.03)vs.0.07 (0.00,0.41);0.00 (0.00,0.01) vs.0.02 (0.00,0.06),respectively].The level of kynurenic acid and thymine (nmol/mgCr) were significantly higher than the level in the control group [0.04 (0.00,0.43) vs.0.00 (0.00,0.00);7.10 (0.00,14.47) vs.0.00 (0.00,0.22),respectively].All the differences were statistically significant (P ＜ 0.05).ROC curve analysis showed that the area under the curve for the diagnosis of BPD in combination with the four metabolites was 0.857 (95％ CI 0.732 ～0.982).Conclusion Changes in urinary metabolites such as fucose,thymine,kynurenine and tartaric acid in preterm infants may be related to the development of BPD.Early detection of these four metabolites has potential in the early diagnosis of BPD,and may warn against the occurrence of BPD.

The pilot study of the central venous pressure of very low birth weight infant within 1 week after birth / 中国新生儿科杂志

Objective To study the range of central venous pressure (CVP) in very low birth weight (VLBW) infants within the first week after birth.Method From February 2014 to February 2018,50 VLBW infants without serious diseases during the first 7 days of life received umbilical venous catheters were prospectively enrolled.CVPs were measured every 4～6 h.The trend of CVP and the correlation of CVP (within 24 h) and birth weight,gestational age were analyzed.Result A total of 50 VLBW infants and 1 291 CVP measurements were included.The CVP increased slightly within 48 h after birth,and then declined.The 95％CI of CVPs were 3.67～4.21,4.03～4.49,3.90～4.33,3.67～4.19,3.29～3.97,3.14～3.94 and 2.64～ 3.55 cmH2O from day 1 to day 7.No significant correlation existed between CVP in the first day and birth weight,nor gestational age (r=-0.267,P=0.073;r=0.106,P=0.762).Conclusion The CVP of VLBW infants increased slightly within 48 h after birth,and then declined.There was no significant correlation between CVP in the first day and birth weight,nor CVP and gestational age.

Analysis of blood metabolites in preterm infants with bronchopulmonary dysplasia using liquid chromatography-tandem mass spectrometry / 中华围产医学杂志

Objective To analyze the changes in blood metabolites in premature infants with bronchopulmonary dysplasia (BPD) within 36 h and in the 3rd week after birth in order to find new biomarkers for diagnosis of BPD.Methods The BPD group included 20 premature infants (＜32 gestational weeks) hospitalized in the Neonatal Intensive Care Unit (NICU) of the Sixth Affiliated Hospital of Sun Yat-sen University and diagnosed with BPD from January 2014 to October 2016.Another 20 non-BPD premature infants with similar gestational age (within one week) who were admitted during the same period were enrolled in the control group.Blood samples of both groups were collected within 36 h and in the 3rd week after birth.Liquid chromatography-tandem mass spectrometry was used to detect blood metabolites and the obtained data were subjected to metabolomics analysis using orthogonal partial least squares discriminant analysis.Chi-square test (or Fisher's exact test),Mann-Whitney U test or t test was used for statistical analysis.Results (1) Twenty and 11 blood samples were collected within 36 h and in the 3rd week after birth from the BPD and the control group,respectively.Compared with the control group,the interval between premature rupture of membranes and delivery,the average length of hospital stay,non-invasive and invasive mechanical ventilation duration and the total duration of supplemental oxygen during hospitalization in the BPD group were longer [M (P25-P75) or ((x)±s):13.5 (0.0-98.3) vs 0.0 (0.0-0.0) h,Z=3.049;(66.6±20.5) vs (43.9±9.3) d,t=4.574;267.0 (199.5-516.1) vs 110.5 (0.0-238.5) h,Z=-3.428;117.5 (0.0-269.3) vs 0.0 (0.0-72.0) h,Z=-2.785;(1 184.0±386.6) vs (595.9±270.3) h,t=5.576;all P＜0.05].(2) Within 36 h after birth,the levels of glycine,proline,tryptophan and piperamide-C5:1 in the BPD group were decreased obviously compared with those in the control group [(201.59±65.01) vs (290.90± 137.56) μmol/L,t=-2.625;103.55 (72.43-434.57) vs 439.48 (103.80-608.98) μ mol/L,Z=-2.245;29.54 (20.30-41.04) vs 47.42 (29.46-73.57) μ mol/L,Z=-2.326;50.04 (35.29-104.78) vs 95.79 (76.21-129.97) μmol/L,Z=-2.029;all P＜0.05].However,the glutamate level was increased [(224.30±67.40) vs (182.67±40.87) μmol/L,t=2.362,P＜0.05].(3) In the 3rd week after birth,the levels of glycine,proline and tryptophan in the BPD group were lower compared to those in the control group [(185.92±61.51) vs (271.85± 115.85) μmol/L,t=-2.177;(39.41± 18.22) vs (63.92± 17.50) μ mol/L,t=-3.217;90.23 (37.93-146.37) vs 330.15 (47.79-622.90) μ mol/L,Z=-2.134;all P＜0.05].However,the ornithine level was higher [(75.09± 43.21) vs (39.25 ± 16.53) μ mol/L,t=2.569,P＜0.05].Conclusions Glycine,proline and tryptophan in blood are potential biomarkers for early diagnosis of BPD.