The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H₂S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H₂S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2A^EC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H₂S signaling pathway. A robust reduction in endothelial MPST-dependent H₂S production followed PP2A deficiency. Exogenous H₂S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2A^EC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H₂S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.

Objective To investigate the application value of 320-slice wide-detector multi-phase left at-rial appendage computed tomography angiography(LAA-CTA)with pulmonary artery(PA)monitoring in the preoperative evaluation of left atrial appendage closure.Methods A retrospective analysis was conducted on the clinical data of 110 patients who underwent LAA-CTA before left atrial appendage closure.Among them,47 patients underwent single-phase enhanced scanning with superior vena cava(SVC)monitoring(con-trol group),and 63 patients underwent multi-phase enhanced scanning with pulmonary artery monitoring(study group).The differences in imaging effects of the left atrial appendage under different monitoring points and phase imaging methods were compared,as well as the accuracy of comparing with the diagnostic results of transesophageal ultrasound(TEE),and the differences in the presentation of thrombus,perithrombus,and hypoperfusion areas in the left atrial appendage.Results The study group could comprehensively display the multi-phase CT value changes of different components(thrombus,peri-thrombotic viscosity,normal blood)within the left atrial appendage cavity,and its evaluation of lesion size and progression was superior to that of the control group.Using TEE as the gold standard,the study group demonstrated better diagnostic ac-curacy for different components and normal regions within the left atrial appendage cavity compared to the control group(P<0.001).Additionally,the study group improved the detection rate of peri-thrombotic vis-cosity,clearly delineated thrombus boundaries,and enhanced diagnostic accuracy(P<0.001).Conclusion Multi-phase LAA-CTA with pulmonary artery monitoring can effectively evaluate the morphological dimensions,thrombus,and peri-thrombotic CT manifestations of the left atrial appendage.It is simple to operate,with an accuracy rate close to the gold standard,providing reliable imaging evidence for preoperative evaluation of left atrial appendage closure.

Objective:To explore the high-risk factors for parenteral nutrition associated cholestasis（PNAC）in extremely/ultra-low birth weight infants，and establish a risk Alignment Diagram prediction model.Methods:We retrospectivly analyzed the clinical data of hospitalized extremely/ultra-low birth weight infants admitted to Neonatology Department at Quanzhou Children's Hospital from January 2019 to December 2020，using multivariate Logistic regression analysis to screen for independent risk factors for the occurrence of PNAC.An Alignment Diagram model prediction model for PNAC was constructed by using R software，and the performance of the model was evaluated through receiver operating characteristic curves.Results:A total of 203 extremely/ultra-low birth weight infants were included，with a median gestational age of 29.14（28.00，30.86）weeks and a median birth weight of 1　170（1　000,1　300）g.Among them，26（12.81%）cases developed PNAC.Multivariate Logistic regression analysis showed that the duration of parenteral nutrition（ OR=1.015 ，95% CI 1.003-1.034），the cumulative amount of glucose（ OR=1.014 ，95% CI 1.001-1.028），small for gestational age（ OR=3.455 ，95% CI 1.127-10.589），and neonatal sepsis（ OR=3.142 ，95% CI 1.039-9.503）were independent risk factors for PNAC（ P＜0.05）；The four independent risk factors mentioned above were introduced into R software to construct an Alignment Diagram model，the area under the receiver operating characteristic curve was 0.835（95% CI 0.842-0.731），and the results of the Hosmer Limeshow goodness of fit test show that：χ 2=5.34，degree of freedom=8， P=0.72.A calibration curve indicated good consistency between the predicted probability of the model and the actual occurrence rate，with good accuracy. Conclusion:The Alignment Diagram model constructed based on four independent risk factors of the duration of parenteral nutrition，glucose accumulation，small for gestational age infants，and neonatal sepsis exhibits high predictive ability，and is expected to provide an intuitive and convenient visualization tool for preventing or reducing the occurrence of PNAC in extremely/ultra-low birth weight infants

Background Chronic low-level exposure to lead can damage the central nervous system and cause anxiety-like behavior. However, whether changes of blood metabolites occur in this process and its relationship with lead-induced neurobehavioral disorder remain unclear. Objective To explore the effects of chronic lead acetate (PbAc) exposure at different concentrations on anxiety-like behavior and serum metabolites and their relationships in mice, as well as the mechanism of lead exposure on neurobehavioral injury in mice from the perspective of metabolomics. Methods A total of 64 healthy 4-week-old C57BL/6J mice, half male and half female, were randomly divided into four groups: control group (normal drinking water), 20 mg·L⁻¹ PbAc group, 100 mg·L⁻¹ PbAc group, and 500 mg·L⁻¹ PbAc group. After 10 weeks of free drinking of water containing designed concentrations of PbAc, the mice were tested for anxiety-like behavioral changes by open field experiment. After the mice were anesthetized, blood was collected from the eyes, the serum was separated, and the effects of designed doses of lead exposure on metabolites in the serum of mice were compared by liquid chromatography with tandem mass spectrometry combined with principal component analysis and partial least squares discrimination analysis. Results The results of the open field experiment showed that the reductions in movement time spent in central area in the 100 mg·L⁻¹ and 500 mg·L⁻¹ PbAc groups compared with the control group were of statistical significance (P<0.05); the reduction in crossing times of central region in the 500 mg·L⁻¹ PbAc group was statistically significant compared with the control group (P<0.05); the increases in defecation frequency in the 100 mg·L⁻¹ and 500 mg·L⁻¹ PbAc groups were statistically significant compared to the control group (P<0.05). In both positive and negative ion modes, compared with the control group, 157 differential metabolites were screened out in the 20 mg·L⁻¹ PbAc group, of which 80 were up-regulated and 77 were down-regulated; 172 differential metabolites were screened out in the 100 mg·L⁻¹ PbAc group, of which 57 were up-regulated and 115 were down-regulated; 119 differential metabolites were screened out in the 500 mg·L⁻¹ PbAc group, of which 42 were up-regulated and 77 were down-regulated. The results of the KEGG enrichment analysis on the differential metabolites revealed alterations in metabolic pathways mainly involving primary bile acid biosynthesis, bile secretion, and cholesterol metabolism. Among the differential metabolites, norethisterone was positively correlated with the number of central region crossings (r=0.406, P<0.05); dihydrothymine was negatively correlated with the number of central region crossings (r=−0.346, P<0.05); lysophosphatidylcholine 22∶1 and lysophospholipid 14∶0 were negatively correlated with time spent in central region (r=−0.429, P<0.05; r=−0.374, P<0.05). Conclusion Chronic lead exposure induces anxiety-like behavior in mice, and this altered behavior is associated with altered metabolites in serum, with differential metabolites enriched primarily in the metabolic pathways of primary bile acid biosynthesis, bile acid secretion, and cholesterol metabolism.

Objective:To analyze the dosimetric differences of volumetric modulated arc therapy (VMAT) plans for lung cancer caused by different dose calculation algorithms and radiation field settings and thus to provide a reference for designing clinical VMAT plans for lung cancer.Methods:This study randomly selected 20 patients with lung cancer and divided them into four groups of VMAT plans, namely, a group adopting two fields and two arcs based on the AAA algorithm (2F2A_AAA), a group employing two fields and two arcs based on the AXB algorithm (2F2A_AXB), a group using two fields and two arcs based on the MC algorithm (2F2A_MC), and a group adopting one field and two arcs based on the MC algorithm (1F2A_MC). Then, this study evaluated the target coverage, high-dose control, dose homogeneity index (HI), conformity index (CI), and organs at risk (OARs) of the plans using different algorithms and radiation field settings.Results:The planning target volume (PTV) results of two fields combined with two arcs (2F2A) of three groups using different algorithms are as follows. 2F2A_MC achieved better results in both D1% and V 95% (the relative volume of the target volume surrounded by 95% of the prescribed dose) of planning gross target volume (PGTV) than 2F2A_AAA (D1%: t=-2.44, P=0.03; V95%:z=-2.04, P=0.04) and 2F2A_AXB (D1%: t=2.34, P=0.03; z=-3.21, P < 0.01). 2F2A_AXB outperformed 2F2A_AAA ( z=-3.66, P < 0.01) and was comparable to 2F2A_MC in terms of the CI of PGTV. Regarding OARs, 2F2A_AXB and 2F2A_MC decreased the V5 Gy of the whole lung by 0.68% ( z=-2.69, P=0.01) and 3.05% ( z=-3.52, P < 0.01), respectively compared to 2F2A_AAA. 2F2A_AXB achieved a whole-lung Dmean of 1776.44 cGy, which was superior to that of 2F2A_MC ( t=2.67, P=0.02) and 2F2A_AAA ( t=8.62, P < 0.01). Compared to 2F2A_AAA and 2F2A_MC, 2F2A_AXB decreased the V20 Gy of Body_5 mm by 1.45% ( z=-3.88, P < 0.01) and 2.01% ( z=-3.66, P < 0.01), respectively. The results of the two groups with different field settings showed that 1F2A_MC was superior to 2F2A_MC in both the CI of PTV1 and the HI of PTV2 (CI: t=2.61, P=0.02; HI: z=-2.20, P=0.03). Moreover, 1F2A_MC increased the Dmean of the whole lung by 26.29 cGy compared to 2F2A_MC ( t=2.28, P=0.04). Conclusions:Regarding the design of VMAT plans for lung cancer, the MC algorithm is suitable for the target priority and the AXB algorithm is suitable for the OAR priority. When only the MC algorithm is available, it is recommended to choose 1F2A in the case of target priority and select 2F2A in the case of OAR priority.

Objective:To investigate the factors related to child care environment and the association between child care environment and children′s early development.Methods:Using stratified cluster random sampling, a total of 22 509 children newly enrolled to kindergarten from 187 kindergartens of 16 districts in Shanghai in 2017 were enrolled. A survey was conducted by parent-reported questionnaire. The index of child care environment (ICCE) and the early human capacity index were used to evaluate family child care environment and children′s early development respectively. The sample was divided into four groups based on the ICCE score: the lowest family childcare environment (ICCE≤10 scores), lower middle (ICCE=11 scores), upper middle (ICCE=12 scores), and the highest (ICCE=13 scores). The linear regression model and Logistic regression model were used to analyze the factors related to child care environment and the association between child care environment and children′s early development respectively.Results:A total of 22 067 children aged (44±7) months, including 11 425 boys (51.8%) and 10 642 girls (48.2%), participated in this study. The multnomial linear regression revealed girls, higher maternal education, higher household annual income, single-child, non-divorced parents, and early breastfeeding experience were protective factors of child care environment for children newly enrolled to kindergarten ( β=0.064, 0.238, 0.119, 0.096, 0.113, and 0.032; 95% confidence interval ( CI): 0.020-0.108, 0.175-0.302, 0.058-0.180, 0.046-0.146, -0.012-0.242, and -0.051-0.116; all P<0.01). The multinomial Logistic regression revealed compared with the highest child care environment group, the odds ratio of children′s early development risks in upper midclle, lower middle, and the lowest child care environment groups were 1.543 (95% CI: 1.373-1.735, P<0.01), 2.537 (95% CI: 2.254-2.856, P<0.01), and 4.198 (95% CI: 3.757-4.690, P<0.01), respectively. Conclusions:The child care environment is not only significantly related to family structure and socioeconomic status, but also to early breastfeeding experience. The child care environment plays an important role in promoting childhood early development.

Objective To analyze the resting-state functional connectivity of the left posterior inferior frontal gyrus in normal subjects with functional MRI and to investigate its preliminary application in post-stroke aphasia.Methods Eleven male patients with post-stroke aphasia and 11 male normal subjects were recruited in this study.Resting-state fMRI data were obtained with GE 1.5 T Twin speed MR Scanner.The fMRI data were processed with SPM2, AFNI and Matlab programs.Based on the results of previous fMRI study with category member generation task , the region of interest ( ROI ) was created in the left posterior inferior frontal gyrus The time course correlations between the ROI and other voxels within whole brain were analyzed.Intra-and inter-group analysis was performed with single sample t-test and two sample t-test.Results Brain regions showed positive resting-state functional connectivity with the ROI in normal subjects including left inferior/middle frontal gyrus , left premotor cortex , left precuneus , left insula , left putamen, right inferior frontal gyrus, right cerebellum and bilateral inferior parietal lobules (voxels 33-809, t=5.80-23.55,P<0.005,uncorrected).Brain regions functionally connected with the ROI in patients with post-stroke aphasia included left inferior/middle frontal gyrus , left premotor cortex , left precuneus , left inferior parietal lobules and right inferior frontal gyrus ( voxels 34-833, t =5.08-20.34, P<0.005, uncorrected ).The left fusiform gyrus was the only region showed significantly decreased functional connectivity with the ROI in the patients group (voxels 84,t=6.25,P<0.005, uncorrected).Conclusions The neural network related to language output exists in normal subjects at the resting-state.Resting-state functional connectivity can be used to investigate the neural mechanism of development and restoration of post-stroke aphasia.

BACKGROUNDThere is no large population-based study of the distribution and changing trend of strabismus surgeries in China. This study aimed to investigate the distribution and the changing trend of strabismus surgery in a tertiary hospital of China.

METHODSA retrospective study of all the strabismus surgeries performed in Beijing Tongren Eye Center from 2003 to 2012 was carried out. Characteristics analyzed included the type of strabismus, age, and gender.

RESULTSTotally 26 524 strabismus surgeries were performed in Tongren Eye Center during the 10-year period. The number of surgeries increased steadily from 1 507 in 2003 to 3 482 in 2008 and slightly decreased to 3 124 in 2009, but there was a sharp drop to 2 569 in 2010 and then kept relatively steady at 2 760 in 2011 and 2 463 in 2012. Intermittent exotropia (30.3%) was the most common among all kinds of strabismus. The number of strabismus surgeries performed on children under 12 years of age (43.60%) was significantly higher than those of the other age groups (P < 0.05). Unilateral superior oblique paralysis was the most common subtype of paralytic strabismus (8.64%).

CONCLUSIONSThe type distribution of strabismus surgery has changed during the recent decade. The age and type distribution of different strabismus remained basically constant, among which intermittent exotropia was the most common.

Child ; Child, Preschool ; China ; Female ; Humans ; Infant ; Male ; Oculomotor Muscles ; Retrospective Studies ; Strabismus ; surgery ; Tertiary Care Centers ; statistics & numerical data