Thoracic aortic aneurysm (TAA) significantly endangers the lives of individuals with Marfan syndrome (MFS), yet the intricacies of their biomechanical origins remain elusive. Our investigation delves into the pivotal role of hemodynamic disturbance in the pathogenesis of TAA, with a particular emphasis on the mechanistic contributions of the mammalian target of rapamycin (mTOR) signaling cascade. We uncovered that activation of the mTOR complex 1 (mTORC1) within smooth muscle cells, instigated by the oscillatory wall shear stress (OSS) that stems from disturbed flow (DF), is a catalyst for TAA progression. This revelation was corroborated through both an MFS mouse model (Fbn1 ^+/C1039G) and clinical MFS specimens. Crucially, our research demonstrates a direct linkage between the activation of the mTORC1 pathway and the intensity in OSS. Therapeutic administration of rapamycin suppresses mTORC1 activity, leading to the attenuation of aberrant SMC behavior, reduced inflammatory infiltration, and restoration of extracellular matrix integrity-collectively decelerating TAA advancement in our mouse model. These insights posit the mTORC1 axis as a strategic target for intervention, offering a novel approach to manage TAAs in MFS and potentially pave insights for current treatment paradigms.

Objective:To design a pediatric early warning score (PEWS) ruler and observe the effect of its application in the nursing of critically ill children hospitalized in neurology department.Methods:A total of 200 critically ill children admitted to Department of Neurology of Hunan Children′s Hospital from 2018 to 2019. 98 cases who were hospitalized from January to September 2019 were selected as the observation group, and 102 cases who were hospitalized from January to September 2018 were set as the control group. The control group received conventional care, while the observation group conducted PEWS ruler for nursing intervention on the basis of conventional care. The differences in hospital days, ICU transfer rate, and frequency of medical intervention between the two groups were compared.Results:The hospital days of the control group and observation group were 18.17 ± 6.33 and 13.33 ± 6.38 respectively, and the difference between the two groups was significant ( t=5.38, P<0.01). The ICU transfer rate was significantly different between the control group 17.6% (18/102) and observation group 8.2% (8/98) ( χ2=3.98, P<0.05). The reduction of increased intracranial pressure, cooling, calm, sedation and oxygen breathing in the control group were 6.86% (7/102), 13.73% (14/102), 6.86% (7/102), 7.84% (8/102), while the observation group were 17.35% (17/98), 27.55% (27/98), 24.49% (24/98), 28.57% (28/98), and the differences between the two groups were significant ( χ2 values were 5.20-14.55, all P<0.05). Conclusions:The application of PEWS ruler is helpful for nurses to recognize the progress of diseases of the critically ill children. Also, it can shorten the hospitalization days of these children, reduce the ICU transfer rate, as well as improve the nursing quality for them.

Objective:To analyze the needle and syringe exchange programme (NSEP) implementation among injecting drug users (IDUs) in China and provide data support and a scientific reference for intervention among IDUs.Methods:All the statistical reports of high-risk behavior interventions during 2007-2021 were collected from the HIV/AIDS Comprehensive Response Information Management System. Descriptive analysis was used to analyze the changes in the number of NSEP points, regional distribution of NSEP points, the number of people covered, and the HIV detection rate in China from 2007 to 2021. Excel 2016 software was used to plot the variation trend. SAS 9.4 software was used for the needle recovery and HIV-positive detection rate to do the χ2 trend test. Results:There were 578 NSEP sites in 11 provinces (autonomous regions and municipalities) by the end of 2021, covering 21 215 IDUs. 2014-2021, the number of NSEP sites and the number of IDUs covered decreased year by year. Each injecting drug user participating in NSEP received more than 200 clean needles annually. The needle recovery rate showed an increasing trend( Z=170.26, P<0.001) from 2009 to 2016 but showed a decreasing trend ( Z=-91.96, P<0.001) from 2016 to 2021. The rate of HIV-positive in IDUs participating in NSEP showed a downward trend ( Z=-66.53, P<0.001), which decreased from 5.8% (2 709/46 591) in 2011 to 0.1% (19/21 215) in 2021, decreasing 98.3%. Conclusions:NSEP is a vital intervention to prevent HIV transmission through injecting drugs. There were still many difficulties. It is necessary to strengthen further communication and coordination with government and public security departments to understand and support for NSEP. Targeted publicity and education are needed to be carried out for local IDUs to encourage them to participate in NSEP and reduce their dropout. Meanwhile, peer educators supervision and management also need to be strengthened.

OBJECTIVE: To analyze the accuracy and positive rate of ultrasound-guided fine-needle aspiration (US-FNA) cytology for detecting suspected thyroid cancer nodules of different sizes. METHODS: A total of 591 patients with 594 suspected malignant thyroid nodules received examinations with US-FNA cytology. Based on their size, the nodules were divided into group I (4-5 mm), group II (6-10 mm), group III (>10 mm). With the results of pathology as the standard, we analyzed the results of US-FNA cytology for detecting thyroid carcinoma in terms of its accuracy, indeterminate rate, positive predictive value and negative predictive value for nodules of different sizes. RESULTS: The positive rates in group I, group II and group III were 39.2% (40/102), 48.2% (172/357) and 65.2% (88/135), respectively, similar between groups I and II (=0.107) and differed significantly between groups I and III (=0.000) and between groups II and III (=0.001). The accuracy, indeterminate rate, positive predictive value and negative predictive value in the 3 groups were 95.5% (21/22), 97.1% (100/103), and 94.4% (51/54); 2.9% (3/102), 2.8% (10/357), and 1.5% (2/135); 100%, 100%, and 98%; 66.7%, 57.1%, and 33.3%, respectively, showing no significant differences among the 3 groups. CONCLUSIONS The size of the thyroid nodules can affect the positive rate but does not have significant effects on the accuracy, indeterminate rate, positive predictive value or negative predictive value of US-FNA cytology.
Biopsy, Fine-Needle ; Humans ; Retrospective Studies ; Thyroid Neoplasms ; Thyroid Nodule ; Ultrasonography, Interventional

Objective To study the relationship between uridine diphosphate glucuronic acid (UGT1A1) gene polymorphism and unexplained neonatal unconjugated hyperbilirubinemia in Jinhua.Method Full-term infants with unidentified non-binding hyperbilirubinemia were selected as hyperbilirubinemia group from January 2016 to December 2017 in the obstetrics or neonatal intensive care unit of Jinhua Central Hospital,healthy full-term neonates and those with physiological jaundice admitted during the same period were selected as control group.Whole blood DNA was extracted and UGT1A1 was sequenced and then annotated with human gene mutation database.The distribution and frequency of UGT1A1 genotype were analyzed.The correlation between different genotypes and unexplained unconjugated hyperbilirubinemia in neonates was also studied.Result Two hundred and forty cases were enrolled in the hyperbilirubinemia group,and 216 cases were enrolled in the control group.Four single nucleotide variation (SNV) sites associated with the disease were found on UGT1A1,which were c.211G＞A (Gly71Arg),c.686C＞A (Pro229Gln),c.1091C＞T (Pro364Leu) and c.1456T＞G (Tyr486Asp),accounting for 83.9％(141/168),1.8％(3/168),8.9％(15/168) and 5.4％(9/168) in the experimental group respectively.The genotype frequency and allele frequency analysis showed that the distribution of the two SNV sites of c.211G＞A and c.1456T＞G were statistically different between the experimental group and the control group (P＜0.05),whereas there was no statistical difference of the other two SNV sites of c.686C＞A and c.1091C＞T between the two groups.Binary Logistic regression analysis showed that c.211G＞A and c.1456T＞G were related to the occurrence of unexplained hyperbilirubinemia,The OR values (95％CI) were 5.412 (3.567～ 8.212) and 8.377 (1.052～66.670) respectively,but no correlation was found of the other two polymorphic loci.At the different genotypes of c.211G＞A locus,the levels of total bilirubin and non-binding bilirubin in infants with homozygous mutant (AA) were higher than those in infants with heterozygous mutant (GA) and wild type (GG),which was statistically significant (P＜0.05).Conclusion The most common mutation site of the UGT1A1 gene in Jinhua is c.211G＞A.The mutations of c.211G＞A and c.1456T＞G are risk factors forunconjugated hyperbilirubinemia in neonates.Of the different genotypes of c.211G＞A locus,the serum bilirubin level of homozygous mutant group was significantly higher than heterozygous mutant group and wild type group.

OBJECTIVE: To analyze the clinical characteristics and genetic basis of a child affected with Glass syndrome. METHODS: Clinical manifestations and auxiliary examination results of the child were analyzed. Potential mutation was detected with next generation sequencing and validated by Sanger sequencing. RESULTS: The child has featured growth and mental retardation, delayed speech, cleft palate, crowding of teeth, and downslanting palpebral fissures. DNA sequencing revealed a de novo heterozygous missense mutation c.1166G>A (p.R389H) in exon 8 of the SATB2 gene in the child. CONCLUSION The heterozygous mutation c.1166G>A (p.R389H) of the SATB2 gene probably account for the Glass syndrome in the patient.
Abnormalities, Multiple ; genetics ; Child ; Chromosome Deletion ; Chromosomes, Human, Pair 2 ; Humans ; Intellectual Disability ; genetics ; Matrix Attachment Region Binding Proteins ; genetics ; Mutation ; Transcription Factors ; genetics

Tung tree (Vernicia fordii) is an economically important woody oil plant that produces tung oil rich in eleostearic acid. Here, we report a high-quality chromosome-scale genome sequence of tung tree. The genome sequence was assembled by combining Illumina short reads, Pacific Bio-sciences single-molecule real-time long reads, and Hi-C sequencing data. The size of tung tree gen-ome is 1.12 Gb, with 28,422 predicted genes and over 73％ repeat sequences. The V. fordii underwent an ancient genome triplication event shared by core eudicots but no further whole-genome duplication in the subsequent ca. 34.55 million years of evolutionary history of the tung tree lineage. Insertion time analysis revealed that repeat-driven genome expansion might have arisen as a result of long-standing long terminal repeat retrotransposon bursts and lack of efficient DNA deletion mechanisms. The genome harbors 88 resistance genes encoding nucleotide-binding sites;17 of these genes may be involved in early-infection stage of Fusarium wilt resistance. Further, 651 oil-related genes were identified, 88 of which are predicted to be directly involved in tung oil biosynthesis. Relatively few phosphoenolpyruvate carboxykinase genes, and synergistic effectsbetween transcription factors and oil biosynthesis-related genes might contribute to the high oil content of tung seed. The tung tree genome constitutes a valuable resource for understanding genome evolution, as well as for molecular breeding and genetic improvements for oil production.

Objective To evaluate the effect of hyperbaric oxygen (HBO) therapy on postoperative cognitive dysfunction (POCD) in elderly patients undergoing general anesthesia.Methods A total of 112 patients,aged 65-75 yr,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,undergoing elective non-cardiac surgery with general anesthesia,were randomly divided into control group (C group,n =54) and HBO group (n =58).Patients were exposed to hyperbaric oxygen in a hyperbaric oxygen chamber once a day from day 3 to day 12 after surgery in both groups.Pressure was slowly increased to 2 atmosphere absolute within 20 min,pure oxygen was inhaled for 35 min by mask,5 min later pure oxygen was inhaled for another 35 min,oxygen inhalation was then stopped and pressure was slowly increased to 1 atmosphere absolute in HBO group.Patients inhaled air at 1 atmosphere absolute for 70 min in C group.Cognitive function score was assessed using Mini-Mental State Examination,language ability test,visual identification function test,digit span backwards task and Hasegawa's Dementia Scale (HDS) at 2 days before surgery and 7 and 13 days after surgery.The development of POCD was recorded.Results Compared with the baseline at 2 days before surgery,language ability test,digit span backwards task and HDS scores were significantly decreased at 7 and 13 days after surgery in C group,and digit span backwards task scores were significantly decreased at 7 days after surgery in HBO group (P＜0.05 or 0.01).The language ability test and HDS scores were significantly higher,and the incidence of POCD was lower at 7 and 13 days after surgery in HBO group than in C group (P＜0.05).Conclusion HBO therapy can reduce POCD in elderly patients undergoing general anesthesia.

Objective To explore the influence of LPS treatment on related molecules in Smads and ERK1/2 signal pathway in pancreatic stellate cell line LTC-14.Methods LTC-14 cells were cultured in vitro, and were treated with LPS at different dose in different time points.Protein expressions of related molecules in Smads pathway and ERK1/2 pathway and α-SMA in LTC-14 Cells were examined by Western blot.Results On Treated LTC-14 cells by 0, 1, 5, 10, 20 and 50 mg/L LPS,protein expressions of Smad3 were 0.15±0.02, 0.37±0.02, 0.44±0.01, 0.46±0.02, 0.372±0.01 and 0.24±0.03;expressions of Smad7 were 0.79±0.05, 0.84±0.02, 0.55±0.03, 0.45±0.03, 0.34±0.02 and 0.92±0.07;p-ERK1/2 levels were 0.48±0.05, 0.74±0.03, 0.72±0.04, 0.89±0.02, 0.81±0.02 and 0.72±0.03;p-cPLA2 levels were 0.15±0.03, 0.30±0.01, 0.31±0.01, 0.30±0.02, 0.28±0.03 and 0.32±0.02;α-SMA levels were 0.56±0.06, 0.62±0.06, 0.54±0.04, 1.03±0.11, 1.39±0.08 and 1.28±0.10.The changes of protein expressions before and after LPS treatment were obvious (all P<0.01).The protein expressions of ERK1/2 were 0.56±0.03, 0.57±0.02, 0.53±0.02, 0.58±0.02, 0.59±0.05 and 0.55±0.04, which did not change obviously along with increased LPS dosages.LTC-14 cells treated with 10 mg/L LPS for 0, 1, 3, 6 and 9 h,the expressions of Smad3 were 0.69±0.05, 0.68±0.07, 1.02±0.14, 1.82±0.0 and 2.04±0.11,those of Smad7 were 2.77±0.10, 1.37±0.08, 1.45±0.14, 0.78±0.09 and 0.63±0.06,those of p-ERK1/2 were 0.16±0.03, 0.32±0.05, 0.79±0.03, 1.50±0.07 and 1.77±0.04,those of p-cPLA2 were 0.15±0.04, 0.32±0.06, 0.63±0.04, 0.95±0.04 and 1.49±0.10,those of α-SMA were 0.84±0.03, 1.26±0.21, 1.81±0.19, 4.28±0.26 and 4.37±0.15, all of which changed obviously as the treatment time increased (P<0.05 or 0.01).The expressions of ERK1/2 were 0.75±0.03, 0.72±0.02, 0.80±0.04, 0.74±0.03 and 0.85±0.09, which did not change obviously as the treatment time increased.Conclusions LPS could upregulate the expression of α-SMA in a time-and dose-dependent way, and activate intracellular Smads and ERK1/2 inflammatory pathways, which may be the potential molecular mechanism of the development of chronic pancreatitis.

Objective To investigate the feasibility, safety and technical superiority of mechanical thrombectomy using a direct aspiration first-pass thrombectomy (ADAPT) in treatment of patients with acute cerebral artery occlusion. Methods A retrospective study was conducted on all patients with acute ischemic stroke treated with mechanical thrombectomy in our institution from January 2013 to August 2016.Patients using ADAPT or stent retriever as a first-line endovascular procedure were compared for clinical characteristics, procedural variables and clinical outcomes. The technical superiority of ADAPT was analyzed in depth. Results During observation period, a total of 91 cases were performed endovascular treatment with mechanical thrombectomy. ADAPT was designed in 46 cases as a first-line endovascular procedure and was utilized in 38 cases (82.6%;ADAPT group), while primary stent retriever thrombectomy was performed in 21 patients(stent group). There was no significant difference in baseline clinical or radiographic factors between ADAPT and stent groups. Although rates of good neurological outcome (modified Rankin Scale(mRS) score≤2) at 90 days were similar between the ADAPT and stent groups (61%(23/38) vs 48%(10/21), P=0.247), National Institute of Health Stroke Scale (NIHSS) score at seven days (6.0(2.0, 9.3) vs 9.0(5.5, 18.5),Z=-2.031,P=0.021) and full recovery rate of neurological outcome (mRS score=0, 37%(14/38) vs 10%(2/21), P=0.022) were significantly better in the ADAPT group than in the stent group. There were no significant differences in rates of embolus to new territory (21%(8/38) vs 29%(6/21), P=0.365), Thrombolysis In Cerebral Infarction (TICI) 2b/3 grade revascularization (84%(32/38) vs 81%(17/21), P=0.507) and symptomatic intracerebral hemorrhage (0%(0/38) vs 10%(2/21), P=0.123) between the ADAPT and the stent groups, but the figures were better in the ADAPT group. Conclusions Mechanical thrombectomy using ADAPT is feasible and safe compared with stent retriever, with higher full recovery rate of neurological outcome and better NIHSS score.It is a method worthy of further exploration for endovascular mechanical recanalization.