[Clinical efficacy of mild therapeutic hypothermia with different rewarming time on neonatal hypoxic-ischemic encephalopathy: a prospective randomized controlled study]. / æ–°ç”Ÿå„¿ç¼ºæ°§ç¼ºè¡€æ€§è„‘ç— ä¸åŒå¤æ¸©æ—¶é—´äºšä½Žæ¸©æ²»ç–—ä¸´åºŠæ•ˆæžœçš„å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To investigate the clinical efficacy of mild therapeutic hypothermia (MTH) with different rewarming time on neonatal hypoxic-ischemic encephalopathy (HIE). METHODS: A prospective study was performed on 101 neonates with HIE who were born and received MTH in Zhongshan Hospital, Xiamen University, from January 2018 to January 2022. These neonates were randomly divided into two groups: MTH1 group (n=50; rewarming for 10 hours at a rate of 0.25°C/h) and MTH2 group (n=51; rewarming for 25 hours at a rate of 0.10°C/h). The clinical features and the clinical efficacy were compared between the two groups. A binary logistic regression analysis was used to identify the factors influencing the occurrence of normal sleep-wake cycle (SWC) on amplitude-integrated electroencephalogram (aEEG) at 25 hours of rewarming. RESULTS: There were no significant differences between the MTH1 and MTH2 groups in gestational age, 5-minute Apgar score, and proportion of neonates with moderate/severe HIE (P>0.05). Compared with the MTH2 group, the MTH1 group tended to have a normal arterial blood pH value at the end of rewarming, a significantly shorter duration of oxygen dependence, a significantly higher proportion of neonates with normal SWC on aEEG at 10 and 25 hours of rewarming, and a significantly higher Neonatal Behavioral Neurological Assessment score on days 5, 12, and 28 after birth (P<0.05), while there was no significant difference in the incidence rate of rewarming-related seizures between the two groups (P>0.05). There were no significant differences between the two groups in the incidence rate of neurological disability at 6 months of age and the score of Bayley Scale of Infant Development at 3 and 6 months of age (P>0.05). The binary logistic regression analysis showed that prolonged rewarming time (25 hours) was not conducive to the occurrence of normal SWC (OR=3.423, 95%CI: 1.237-9.469, P=0.018). CONCLUSIONS: Rewarming for 10 hours has a better short-term clinical efficacy than rewarming for 25 hours. Prolonging rewarming time has limited clinical benefits on neonates with moderate/severe HIE and is not conducive to the occurrence of normal SWC, and therefore, it is not recommended as a routine treatment method.

Ophthalmological outcomes of unilateral coronal synostosis in young children.

BACKGROUND: To report refractive outcomes, describe types of strabismus and evaluate the outcomes of surgical intervention for unilateral coronal synostosis (UCS) in paediatric patients. METHODS: This study retrospectively included 30 UCS cases. Patients aged from 3 months to 6 years (median: 1.8 years) were enrolled from January 2018 to December 2019 at Shanghai Children's Hospital. Sixteen patients had all types of strabismus; 15 of these patients underwent surgery. RESULTS: Refractive errors of 30 cases were included. In 60% of patients, astigmatism of 1.00D or more existed in not less than one eye at last record. Twenty (66.7%) patients had the larger amount of astigmatism in the contralateral eye. Fifteen patients received strabismus surgery, of whom 6 patients with monocular elevation deficiency (MED) underwent the standard Knapp procedure, with or without a horizontal deviation procedure. Fifteen cases were horizontally aligned within 5 prism dioptres (Δ). Six patients with MED (100%) had attained ≥25% elevation improvement after surgery, and the vertical deviation decreased from 25.83 Δ ± 4.92 Δ (range, 20 Δ-30 Δ) to 0.83 Δ ± 4.92 Δ after surgery (range, 0 Δ-10 Δ), for an improvement of 26.67 Δ ± 4.08 Δ (t = 16 P < 0.05). In 1 patient with esotropia, the horizontal deviation decreased from + 80 Δ to + 5 Δ after surgery. One patient was diagnosed with trichiasis and one with contralateral lacrimal duct obstruction. CONCLUSIONS: Contralateral MED was also the main type of strabismus in UCS. Superior oblique muscle palsy was still the most common, as previously reported. There is a risk of developing a higher astigmatism and anisometropia in the contralateral eye to synostosis. Other ophthalmic disorders should be treated in a timely manner. TRIAL REGISTRATION: The study was approved by the Institutional Review Board of Shanghai Children's Hospital (approval No. 2020R023-E01) and adhered to the tenets of the Declaration of Helsinki. Ethics approval was procured on March 30, 2020. This was a retrospective study. Written informed consent was sought from the patients' parents or legal guardians. Clinical Trials Registry number: ChiCTR2000034910 . Registration URL: http://www.chictr.org.cn/showproj.aspx?proj=56726 .

DKK1 inhibits breast cancer cell migration and invasion through suppression of ß-catenin/MMP7 signaling pathway.

BACKGROUND: DKK1 has been reported to act as a tumor suppressor in breast cancer. However, the mechanism of DKK1 inhibits breast cancer migration and invasion was still unclear. METHODS: Western blot and real time PCR was used to detect the expression of DKK1, ß-catenin and MMP7 in breast cancer cells. Wound scratch assay and transwell assay was employed to examine migration and invasion of breast cancer cell. RESULTS: DKK1 overexpression dramatically inhibits breast cancer cell migration and invasion. Knockdown of DKK1 promotes migration and invasion of breast cancer cells. DKK1 suppressed breast cancer cell migration and invasion through suppression of ß-catenin and MMP7 expression. XAV-939, an inhibitor of ß-catenin accumulation could reverse DKK1 silencing-induced MMP7 expression in breast cancer cells. Meanwhile, XAV-939 also could reverse the increase in the cell number invaded through Matrigel when DKK1 was knockdown. Furthermore, depletion of MMP7 also could reverse DKK1 knockdown-induced increase in the cell number invaded through Matrigel. CONCLUSIONS: DKK1 inhibits migration and invasion of breast cancer cell through suppression of ß-catenin/MMP7 pathway, our findings offered a potential alternative for breast cancer prevention and treatment.

Suppression of epidermal growth factor receptor-mediated ß-catenin nuclear accumulation enhances the anti-tumor activity of phosphoinositide 3-kinase inhibitor in breast cancer.

Phosphoinositide 3-kinase (PI3K) signaling is frequently deregulated in breast cancer and plays a critical role in tumor progression. However, resistance to PI3K inhibitors in breast cancer has emerged, which is due to the enhanced ß-catenin nuclear accumulation. Until now, the mechanisms underlying PI3K inhibition-induced ß-catenin nuclear accumulation remains largely unknown. In the present study, we found inhibition of PI3K with LY294002 promoted ß-catenin nuclear accumulation in MCF-7 and MDA-MB-231 breast cancer cells. Combining PI3K inhibitor LY294002 with XAV-939, an inhibitor against ß-catenin nuclear accumulation, produced an additive anti-proliferation effect against breast cancer cells. Subsequent experiments suggested ß-catenin nuclear accumulation induced by PI3K inhibition depended on the feedback activation of epidermal growth factor receptor (EGFR) signaling pathway in breast cancer cells. Inhibition of EGFR phosphorylation with Gefitinib enhanced anti-proliferation effect of PI3K inhibitor LY294002 in MCF-7 and MDA-MB-231 cells. Taken together, our findings may elucidate a possible mechanism explaining the poor outcome of PI3K inhibitors in breast cancer treatment.

[7-hydroxy sulfonation of liquiritigenin by recombinant SULT1A3 enzyme and HEK-SULT1A3 cells].

In this study,liquiritigenin sulfonation was characterized using recombinant human sulfotransferases( SULTs). The chemical structure of liquiritigenin sulfate was determined by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry( UPLC-Q-TOF-MS/MS). Then model fitting and parameter estimation were performed using the Graphpad Prism V5 software. Various SULT enzymes( SULT1 A1,1 A2,1 A3,1 B1,1 C2,1 C4,1 E1 and 2 A1) were able to catalyze the formation of liquiritigenin-7-O-sulfate. Sulfonation of liquiritigenin-7-hydroxy( 7-OH) by these eight SULT enzymes consistently displayed the classical Michaelis-Menten profile. According to the intrinsic clearance( CLint) value,the sulfonation rates of liquiritigenin-7-OH by expressed SULT enzymes followed the following rank order: SULT1 C4 > SULT1 A3 > SULT1 E1 > SULT1 A1 > SULT1 A2 > SULT1 B1 >SULT1 C2>SULT2 A1. Further,liquiritigenin-7-O-sulfonation was significantly correlated with the SULT1 A3 protein levels( P<0. 05).Then,human embryonic kidney( HEK) 293 cells over expressing SULT1 A3( named as HEK-SULT1 A3 cells) were conducted. As a result,liquiritigenin-7-O-sulfate( L-7-S) was rapidly generated upon incubation of the cells with liquiritigenin. Consistent with SULT1 A3,sulfonation of liquiritigenin-7-OH in HEK-SULT1 A3 cells also followed the Michaelis-Menten kinetics. The derived Vmaxvalues was( 0. 315±0. 009) µmol·min-1·g-1,Kmwas( 7. 04±0. 680) µmol·L-1,and CLintwas( 0. 045±0. 005) L·min-1·g-1. Moreover,the sulfonation characters of liquiritigenin( 7-OH) in SULT1 A3 were strongly correlated with that in HEK-SULT1 A3 cells( P<0. 001).The results indicated that HEK-SULT1 A3 cells have shown the catalytic function of SULT1 A3 enzymes. In conclusion,liquiritigenin was subjected to efficient sulfonation,and SULT1 A3 enzyme plays an important role in the sulfonation of liquiritigenin-7-OH. Significant sulfonation should be the main reason for the low bioavailability of liquiritigenin. In addition,HEK-SULT1 A3 cells were conducted and successfully used to evaluate liquiritigenin sulfonation,which will provide an appropriate tool to accurately depict the sulfonation disposition of liquiritigenin in vivo.

[Effect of Qishen Yiqi droplet on adenylate contents in myocardium of cor pulmonale rats].

Cor pulmonale rat models were induced by a single intraperitoneal injection of monocrotaline(MCT), and the sham group received a single intraperitioneal injection of normal saline. After the model rats received intragastric administration of Qishen Yiqi droplet(QS) for 6 weeks, the contents of adenylate(ATP, ADP and AMP) in right myocardial tissues were measured by HPLC, and then the metabolism changes in myocardium of cor pulmonale rats with QS were investigated. The results showed that ATP, ADP, and AMP were well separated, with a good linearity within a certain range of concentration; and the recovery rates were within the range of 90%-108%. As compared with model group, the level of ATP was significantly elevated in high-dose treatment group; ADP contents showed an increasing trend and AMP contents showed a decreasing trend, indicating that QS could significantly improve energy metabolism system in myocardium. By using the HPLC, a qualitative and quantitative analysis method was given for the determination of ATP, ADP and AMP contents in myocardium, providing a method for energy metabolism measurement in biological samples.

Dynamic changes of mononuclear phagocytes in circulating, pulmonary alveolar and interstitial compartments in a mouse model of experimental silicosis.

CONTEXT: Silicosis is a devastating, irreversible lung fibrosis condition exposed to crystalline silica. The mononuclear phagocyte system plays an important role in the pathogenesis of silicosis. OBJECTIVE: The present study was aimed to explore the dynamic changes of mononuclear phagocytes in circulating, pulmonary alveolar and interstitial compartments in experimental silicosis model. MATERIALS AND METHODS: A mouse model of lung fibrosis was developed with crystalline silica particles (2 mg/40 µL via oropharyngeal instillation) using male C57BL/6 mice, and were killed on days 1, 3, 7, 14, and 28. The lung inflammation and fibrosis was investigated using hematoxylin-eosin staining and bronchoalveolar lavage fluid (BALF) analysis, Masson's trichrome staining, and immunofluorescence. Circulating monocyte subsets (Ly6C(hi) and Ly6C(lo)), polarization state of BALF-derived alveolar macrophages (AMϕ) and lung interstitial macrophages (IMϕ, derived from enzymatically digested lung tissue) were analyzed by flow cytometry. RESULTS: The percentage of Ly6C(hi) monocytes significantly increased on day 1 after silica exposure, which reached the peak level from day 7 till day 28. Moreover, M2 (alternative activation) AMϕ (PI - CD64 + CD206+) was dramatically and progressively increased from day 1 to day 28. A parallel increase in IMϕ with M2 polarization (PI-CD64 + CD11b + CD206+) was also observed from day 1 to day 28. CONCLUSION: Our data demonstrate a dynamic view of mononuclear phagocyte change in three compartments after silica challenge, which highlights the remodeling of mononuclear phagocyte system as a potential therapeutic target for silicosis.

Neutrophil extracellular traps in ischemia-reperfusion injury-induced myocardial no-reflow: therapeutic potential of DNase-based reperfusion strategy.

Emerging evidence suggests a potential role of neutrophil extracellular traps (NETs) in linking sterile inflammation and thrombosis. We hypothesized that NETs would be induced during myocardial ischemia-reperfusion (I/R), and NET-mediated microthrombosis may contribute to myocardial "no-reflow". Male Wistar rats were randomly divided into I/R control, DNase (DNase I, 20 µg/rat), recombinant tissue-type plasminogen activator (rt-PA, 420 µg/rat), DNase + rt-PA, and sham control groups after 45-min myocardial ischemia. In situ NET formation, the anatomic "no re-flow" area, and infarct size were evaluated immediately after 3 h of reperfusion. Long-term left ventricular (LV) functional and histological analyses were performed 45 days after operation. Compared with the I/R controls, the DNase + rt-PA group exhibited reduced NET density [8.38 ± 1.98 vs. 26.86 ± 3.07 (per 200 × field), P < 0.001] and "no-flow" area (15.22 ± 0.06 vs. 34.6 ± 0.05%, P < 0.05) in the ischemic region, as well as reduced infarct size (38.39 ± 0.05 vs. 71.00 ± 0.03%, P < 0.001). Additionally, compared with the I/R controls, DNase + rt-PA treatment significantly ameliorated I/R injury-induced LV remodeling (LV ejection fraction: 64.22 ± 3.37 vs. 33.81 ± 2.98%, P < 0.05; LV maximal slope of the LV systolic pressure increment: 3,785 ± 216 vs. 2,596 ± 299 mmHg/s, P < 0.05). The beneficial effect was not observed in rats treated with DNase I or rt-PA alone. Our study provides evidence for the existence of NETs in I/R-challenged myocardium and confirms the long-term benefit of a novel DNase-based reperfusion strategy (DNase I + rt-PA), which might be a promising option for the treatment of myocardial I/R injury and coronary no-reflow.

Research progress in the treatment of chronic fatigue syndrome through interventions targeting the hypothalamus-pituitary-adrenal axis.

Chronic fatigue syndrome (CFS) causes great harm to individuals and society. Elucidating the pathogenesis of CFS and developing safe and effective treatments are urgently needed. This paper reviews the functional changes in the hypothalamus-pituitary-adrenal (HPA) axis in patients with CFS and the associated neuroendocrine mechanisms. Despite some controversy, the current mainstream research evidence indicates that CFS patients have mild hypocortisolism, weakened daily variation in cortisol, a weakened response to the HPA axis, and an increase in negative feedback of the HPA axis. The relationship between dysfunction of the HPA axis and the typical symptoms of CFS are discussed, and the current treatment methods are reviewed.

Greenspace and human microbiota: A systematic review.

BACKGROUND: Potential effect of greenspace exposure on human microbiota have been explored by a number of observational and interventional studies, but the results remained mixed. We comprehensively synthesized these studies by performing a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. METHODS: Comprehensive literature searches in three international databases (PubMed, Embase, and Web of Science) and three Chinese databases (China National Knowledge Infrastructure, Wanfang, and China Biology Medicine disc) were conducted from inception to November 1, 2023. Observational and interventional studies that evaluated associations between greenspace exposure and human microbiota at different anatomical sites were included. Studies were assessed using the National Toxicology Program's office of Health Assessment and Translation risk of bias tool and certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation framework. Two authors independently performed study selection, data extraction, and risk of bias assessment, and evidence grading. Study results were synthesized descriptively. RESULTS: Twenty studies, including 11 observational studies and 9 interventional studies, were finally included into the systematic review. The microbiota of the included studies was from gut (n = 13), skin (n = 10), oral cavity (n = 5), nasal cavity (n = 5) and eyes (n = 1). The majority of studies reported the associations of greenspace exposure with increased diversity (e.g., richness and Shannon index) and/or altered overall composition of human gut (n = 12) and skin microbiota (n = 8), with increases in the relative abundance of probiotics (e.g., Ruminococcaceae) and decreases in the relative abundance of pathogens (e.g., Streptococcus and Escherichia/Shigella). Due to limited number of studies, evidence concerning greenspace and oral, nasal, and ocular microbiota were still inconclusive. CONCLUSION: The current evidence suggests that greenspace exposure may diversify gut and skin microbiota and alter their composition to healthier profiles. These findings would be helpful in uncovering the potential mechanisms underlying greenspace and human health and in promoting a healthier profile of human microbiota.

Clinical characteristics and genetic profiles of 44 patients with severe combined immunodeficiency (SCID): report from Shanghai, China (2004-2011).

Severe combined immunodeficiency (SCID), a rare type of genetic associated immune disorder, is poorly characterized in mainland China. We retrospectively reviewed 44 patients with SCID who received treatment from 2004 to 2011 in Shanghai, China, and herein summarize their clinical manifestations and immunological and preliminary genetic features. The male-to-female ratio was 10:1. Twenty five patients presented with X-SCID symptoms. Only one patient was diagnosed before the onset of symptoms due to positive family history. The mean time of delay in the diagnosis of X-SCID was 2.69 months (range, 0.5-8.67). Thirty-seven of the 44 patients died by the end of 2011 with the mean age of death being 7.87 months (range, 1.33-31). Six patients received hematopoietic stem cell transplantation (HSCT); only one of them survived, who was transplanted twice. The time between onset and death was shorter in the HSCT-treated group compared with the untreated group (2.87 ± 1.28 and 3.34 ± 0.59 months, respectively), probably due to active infections during transplantation. Bacillus Calmette-Guérin (BCG) complications occurred in 14 of the 34 patients who received BCG vaccination. Transfusion-induced graft-versus-host disease occurred in 5 patients. Total 20 mutations in interleukin-2 receptor subunit gamma (IL2RG) were identified in 22 patients, including 11 novel mutations. Most patients were misdiagnosed before referred to our SCID Center. Therefore, establishing more diagnostic centers dedicated to the care of PID and accessible by primary immunodeficiency patients will facilitate early, correct diagnosis and better care of SCID in China.

Role of synaptotagmin 13 (SYT13) in promoting breast cancer and signaling pathways.

PURPOSE: Breast cancer is one of the leading causes of tumor death worldwide in female, and the five-year overall survival of breast cancer patients remains poor. It is an urgent need to seek novel target for its treatment. Synaptotagmin 13 (SYT13) is a synaptic vesicle transporting protein that regulates the malignant phenotypes of various cancers. However, its role in breast cancer is still unclear. The current study aimed to investigate the effects of SYT13 on the progression of breast cancer. METHODS: Twenty-five pairs of breast cancer tissues and non-tumor tissues were obtained to assess the expression of SYT13. We manually modified the expression of SYT13 in MCF-7 and MDA-MB-231 cells. CCK-8 assay, EdU staining, and cell cycle analysis were carried out to measure the proliferated ability of cells. Annexin V/PI and TUNEL assays were used to detect the apoptotic ability of cells. Wound healing and transwell assays were employed to evaluate the migrated and invasive ability of breast cancer cells. RESULTS: The results revealed that the mRNA and protein levels of SYT13 were higher in breast cancer tissues and cell lines. Knockdown of SYT13 inhibited the cell proliferation and induced cell cycle arrest in G1 phase of MCF-7 cells by downregulating cyclin D1 and CDK4, as well as upregulating p21. The migration and invasion of MCF-7 cells were repressed by the loss of SYT13 via the gain of E-cadherin and the loss of vimentin. Overexpression of SYT13 in MDA-MB-231 cells led to the opposite effects. Silencing of SYT13 induced the apoptosis ability of MCF-7 cells by the upregulation of bax and the downregulation of bcl-2. Moreover, we found that SYT13 depletion suppressed the FAK/AKT signaling pathway. PF573228 (a FAK inhibitor) and MK2206 (an AKT inhibitor) reversed the SYT13 overexpression-induced promotion of proliferation, migration, and invasion of MDA-MB-231 cells. CONCLUSION: The results indicated that SYT13 promoted the malignant phenotypes of breast cancer cells by the activation of FAK/AKT signaling pathway.

ZNRF2 as an oncogene is transcriptionally regulated by CREB1 in breast cancer models.

E3 ubiquitin ligase Zinc and Ring Finger 2 (ZNRF2) has been demonstrated to be engaged in the development of multiple cancers. Nevertheless, the function of ZNRF2 in breast cancer (BC) still unclear. In this work, we firstly analyzed the differentially expressed genes in BC by bioinformatics and found that ZNRF2 was highly expressed in BC. Consistently, we further confirmed that ZNRF2 was upregulated in BC tissues compared with adjacent normal tissues, and this was positively correlated with the poor prognosis and the higher pathological grades of patients with BC. Functional assays performed on HCC1937 and MCF-7 cells indicated that silencing of ZNRF2 suppressed cell proliferation, as evidenced by the decrease in the expression of cyclin A, PCNA and cyclin D1. Flow cytometry and Hoechst staining showed that knockdown of ZNRF2 induced cell apoptosis, which was verified by the upregulation of apoptosis genes such as Bax, cleaved PARP and Bim. ZNRF2 knockdown also inhibited in vivo tumor growth. But, instead, ZNRF2-overexpressed BC cells exhibited obvious malignant phenotypes. Additionally, we observed that cAMP response element binding protein 1 (CREB1) directly bound to the promoter sequence of ZNRF2 and thus activating its transcription, suggesting that ZNRF2 is transcriptionally regulated by CREB1. Additionally, ZNRF2 knockdown could reverse the proliferation-promoting action of CREB1 on BC cells, Hence, this study demonstrated that ZNRF2 might serve as a prospective therapeutic target for BC.

An intelligent "chemical tongue" for high-order monitoring ATP-related physiological phosphates and ATP hydrolysis through diverse transduction principles.

For discriminating diverse analytes and monitoring a specific chemical reaction, the emerging multi-channel "chemical nose/tongue" is challenging multi-material "chemical nose/tongue". The former contributes greatly to integrating different transduction principles from a single sensing material, avoiding the need for complex design, high cost, and tedious operation involved with the latter. Therefore, this high-order sensing puts a particular emphasis on the effects of encapsulation. Herein, the plasmonic gold nanoparticles (Au NPs) are encapsulated as a core into the fluorescent guanine monophosphate-Tb3+ infinite coordination polymer nanoparticles (GMP-Tb ICPs) to obtain a core-shell nanocomposite named Au NPs@GMP-Tb ICPs. Hence, a dual-channel "chemical tongue" based on Au NPs@GMP-Tb ICPs is present to realize high-order sensing of adenosine triphosphate (ATP)-related physiological phosphates and the monitoring of ATP hydrolysis. Considering the affinity of Tb3+ towards P-O bonds, four inorganic phosphates and three nucleotide phosphates with different phosphate group numbers and steric hindrance effect directly regulate two stimulus responses (fluorescence intensity and UV-vis absorbance) of Au NPs@GMP-Tb ICPs. Robust statistical methods, such as linear discriminant analysis and hierarchical cluster analysis, are used to recognize each phosphate by the developed sensor array either in the aqueous solution or in complex media such as serum, together with efficiently monitored ATP hydrolysis at different intervals. These findings and blind test clarify that the designed "chemical tongue" guarantees interference resistance and strengthens analytical capacity, together with offering valuable insight into "lab-on-a-nanoparticle" development for monitoring specific chemical reactions.

Global, regional, and national burden of preterm birth attributable to ambient and household PM2.5 from 1990 to 2019: Worsening or improving?

BACKGROUND: Maternal exposure to fine particular matter (PM2.5) during pregnancy, including ambient and household PM2.5, has been linked with increased risk of preterm birth (PTB). However, the global spatio-temporal distribution of PTB-related deaths and disability-adjusted life years (DALYs) attributable to PM2.5 is not well documented. We estimated the global, regional, and national patterns and trends of PTB burden attributable to both ambient and household PM2.5 from 1990 to 2019. METHODS: Based on the Global Burden of Disease Study (GBD) 2019 database, we obtained the numbers of deaths and DALYs as well as age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) of PTB attributable to total, ambient, and household PM2.5 by socio-demographic index (SDI) and sex during 1990-2019. The average annual percentage changes (AAPCs) were calculated to assess the temporal trends of attributable burdens. RESULTS: In 2019, 126,752 deaths and 11.3 million DALYs related to PTB worldwide (two-thirds in Western Sub-Saharan Africa and South Asia) could be caused by excess PM2.5 above the theoretical minimum-risk exposure level (TMREL), of which 39 % and 61 % were attributable to ambient PM2.5 and household PM2.5, respectively. From 1990 to 2019, the global ASMR due to ambient PM2.5 increased slightly by 7.08 % whereas that due to household PM2.5 decreased substantially by 58.81 %, although the latter still dominated the attributable PTB burden, especially in low and low-middle SDI regions. Similar results were also observed for ASDRs. In addition, PTB burden due to PM2.5 was higher in male infants and in lower SDI regions. CONCLUSIONS: Globally in 2019, PM2.5 remains a great concern on the PTB burden, especially in Western Sub-Saharan Africa and South Asia. Between 1990 and 2019, age-standardized burden of PTB due to ambient PM2.5 increased globally, while that due to household PM2.5 decreased markedly but still dominated in low and low-middle SDI regions.

Electrophysiological mechanisms of motion-style scalp acupuncture for treating poststroke spasticity in rats. / è¿åŠ¨å¤´é’ˆæ³•æŠ—å’ä¸­åŽç—‰æŒ›æ•ˆåº”çš„ç”µç”Ÿç†æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To observe the effect of motion-style scalp acupuncture (MSSA) on H-reflex in rats with post-stroke spasticity (PSS), so as to explore the electrophysiological mechanisms of MSSA against spasticity. METHODS: A total of 36 male SD rats were randomly divided into sham operation, model and MSSA groups, with 12 rats in each group. The stroke model was established by occlusion of the middle cerebral artery. After modeling, rats in the MSSA group were treated by scalp acupuncture (manipulated every 15 min, 200 r/min) at ipsilesional "parietal and temporal anterior oblique line" (MS6) for a total of 30 min, the treadmill training (10 m/min) was applied during the needling retention, once daily for consecutive 7 days. The neurological deficits, muscle tone and motor function were assessed by Zea Longa score, modified modified Ashworth scale (MMAS) score and screen test score before and after treatment, respectively. The H-reflex of spastic muscle was recorded by electrophysiological recordings and the frequency dependent depression (FDD) of H-reflex was also recorded. The cerebral infarction volume was evaluated by TTC staining. RESULTS: Compared with the sham operation group, the Zea longa score, MMAS score, cerebral infarction volume, motion threshold, Hmax/Mmax ratio and FDD of H-reflex were significantly increased (P<0.01), while the screen test score was significantly decreased (P<0.01) in the model group. Intriguingly, compared with the model group, the above results were all reversed (P<0.01) in the MSSA group. CONCLUSIONS: MSSA could exert satisfactory anti-spastic effects in rats with PSS, the underlying mechanism may be related to the improvement of nerve function injury, the reduction of spastic muscle movement threshold, Hmax/Mmax ratio and H-reflex FDD.

Global burden and drivers of hyperglycemia: Estimates and predictions from 1990 to 2050.

Hyperglycemia is a key risk factor for death and disability worldwide. To better inform prevention strategies, we aimed to delineate and predict the temporal, spatial, and demographic patterns in mean fasting plasma glucose (FPG) levels and their related disease burden globally. Based on the Global Burden of Disease Study 2019, we estimated the distributions of mean FPG levels and high FPG-related disease burden by age, sex, year, socioeconomic status (SES), and geographical region from 1990 to 2050. We also investigated the possible associations of demographic, behavioral, dietary, metabolic, and environmental factors with FPG levels and high FPG-related disease burden. In 2019, the global mean FPG level was 5.40 mmol/L (95% uncertainty interval [UI]: 4.86-6.00), and high FPG contributed to 83.0 deaths (95% UI, 64.5-107.1) and 2,104.3 DALYs (95% UI: 1,740.7-2,520.7) per 100,000 people. For both historical (1990-2019) and future (2020-2050) periods, the mean FPG levels and the high FPG-related disease burden increased globally, with greater increases among the middle-aged and elderly, and people in low-to-middle SES countries, relative to their counterparts. Aging, unhealthy lifestyles, elevated body mass index, and lower air temperatures were potential risk factors for high FPG levels and the high FPG-related disease burden. This study demonstrates that high FPG continues to contribute to the global disease burden and is expected to do so for at least the next 30 years. Older people and those living in low-to-middle SES countries should receive more attention in glycemic management health interventions. In addition, effective interventions that target identified risk factors should be adopted to handle the increasingly large disease burden of high FPG.

Association between Residential Greenness and Human Microbiota: Evidence from Multiple Countries.

BACKGROUND: Greenness, referring to a measurement of the density of vegetated land (e.g., gardens, parks, grasslands), has been linked with many human health outcomes. However, the evidence on greenness exposure and human microbiota remains limited, inconclusive, drawn from specific regions, and based on only modest sample size. OBJECTIVES: We aimed to study the association between greenness exposure and human microbial diversity and composition in a large sample across 34 countries and regions. METHODS: We explored associations between residential greenness and human microbial alpha-diversity, composition, and genus abundance using data from 34 countries. Greenness exposure was assessed using the normalized difference vegetation index and the enhanced vegetation index mean values in the month before sampling. We used linear regression models to estimate the association between greenness and microbial alpha-diversity and tested the effect modification of age, sex, climate zone, and pet ownership of participants. Differences in microbial composition were tested by permutational multivariate analysis of variance based on Bray-Curtis distance and differential taxa were detected using the DESeq2 R package between two greenness exposure groups split by median values of greenness. RESULTS: We found that higher greenness was significantly associated with greater richness levels in the palm and gut microbiota but decreased evenness in the gut microbiota. Pet ownership and climate zone modified some associations between greenness and alpha-diversity. Palm and gut microbial composition at the genus level also varied by greenness. Higher abundances of the genera Lactobacillus and Bifidobacterium, and lower abundances of the genera Anaerotruncus and Streptococcus, were observed in people with higher greenness levels. DISCUSSION: These findings suggest that residential greenness was associated with microbial richness and composition in the human skin and gut samples, collected across different geographic contexts. Future studies may validate the observed associations and determine whether they correspond to improvements in human health. https://doi.org/10.1289/EHP12186.

Association between long-term green space exposure and mortality in China: A difference-in-differences analysis of national data in 2000, 2010 and 2019.

BACKGROUND: Effects of green space on human health have been well-documented in western, high-income countries. Evidence for similar effects in China is limited. Moreover, the underlying mechanisms linking green space and mortality are yet to be established. We therefore conducted a nation-wide study to assess the association between green space and mortality in China using a difference-in-difference approach, which applied a causal framework and well controlled unmeasured confounding. In addition, we explored whether air pollution and air temperature could mediate the association. METHODS: In this analysis, we collected data on all-cause mortality and sociodemographic characteristics for each county in China from the 2000 and 2010 censuses and the 2020 Statistical Yearbook. Green space exposure was assessed using county-level normalized difference vegetation index (NDVI) and the percentage of green space (forest, grasslands, shrub land and wetland). We applied a difference-in-differences approach to evaluate the association between green space and mortality. We also performed mediation analysis (by air pollution and air temperature). RESULTS: Our sample consisted of 2726 counties in 2000 and 2010 as well as 1432 counties in 2019. In the 2000 versus 2019 comparison, a 0.1 unit increase in NDVI was associated with a 2.4 % reduction in mortality [95 % confidence interval (CI) 0.4-4.3 %], and a 10 % increase in percentage of green space was associated with a 4.7 % reduction (95 % CI 0-9.2 %) in mortality. PM2.5 and air temperature mediated 0.3 % to 12.3 % of the associations. CONCLUSIONS: Living in greener counties may be associated with lower risk of mortality in China. These findings could indicate the potential of a population-level intervention to reduce mortality in China, which has important public health implications at the county level.

[Aryl hydrocarbon receptor interacting protein gene and familial isolated pituitary adenomas].

Familial isolated pituitary adenoma (FIPA) is an autosomal dominant disease, characterized by low penetrance, early-onset disease, more invasive tumor growth, as well as somatotroph and lactotroph adenomas in most cases. It has been indicated that the aryl hydrocarbon receptor interacting protein (AIP) gene is a tumor suppressor gene. Many heterozygous mutations have been discovered in AIP in about 20% of FIPA families. However, the exact molecular mechanism by which its disfunction promotes tumorigenesis of pituitary is unclear.