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Background Previous studies have shown that active smoking during pregnancy can reduce the level of neonatal cord blood leptin, and thereby affect birth weight. However, few studies have studied the association of passive smoking during pregnancy with leptin in neonatal cord blood and birth weight. Objective To explore the effects of passive smoking in varied pregnancy stages and entire pregnancy on neonatal cord blood leptin level and birth weight in a certain rural area of Yunnan, and potential mediating role of cord blood leptin. Methods Based on a prospective prenatal cohort study conducted in Xuanwei County, Yunnan Province, a total of 545 mother-infant pairs were included in this study from early pregnancy enrollment to delivery. The demographic information and reproductive history of the subjects were collected by questionnaire. The urine samples of pregnant women in the first, second, and third trimesters of pregnancy were collected during regular prenatal examinations. Umbilical cord blood samples were collected from newborns at birth. The concentration of urine cotinine (UC) was measured by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). According to the results of UC level during pregnancy, the study subjects were divided into three groups: negative group (<LOD), low exposure group (LOD-M), and high exposure group(>M). The level of leptin in cord blood was detected by ELISA. Multiple linear regression was used to analyze the effect of passive smoking on umbilical cord blood leptin in newborns during pregnancy. Path analysis was used to explore the relationship among passive smoking during pregnancy, neonatal cord blood leptin, and birth weight. Results The average exposure rate of passive smoking during pregnancy was 87.28%, and the exposure rate for entire pregnancy was 76.88%. The median concentration of leptin in neonatal cord blood was 4.17 μg·L−1. After adjusting for maternal age, ethnicity, educational level, pre-pregnancy body mass index (BMI), gestational weight gain, parity, annual household income, infant sex, and birth weight, we found that low level (b=−3.388, P=0.001) and high level (b=−2.738, P=0.006) of passive smoking in the first trimester of pregnancy had negative associations with leptin concentration of cord blood by multiple linear model. The path analysis results showed that passive smoking in the first trimester and pre-pregnancy BMI directly affected leptin levels, and the sizes of direct effects were −0.073 and −0.087 (both P<0.05) respectively. Passive smoking in late pregnancy, gestational weight gain, premature, newborn girls, parity, and pre-pregnancy BMI directly affected birth weight, and the sizes of direct effects were −0.063, 0.191, −0.301, −0.128, −0.121, and 0.167 (all P<0.05), respectively. No mediating role of leptin was found in the effect of passive smoking on neonatal birth weight. Conclusion Passive smoking exposure during pregnancy is common among rural women in Yunnan Province. Passive smoking in the first trimester may be key in decreasing the leptin level of neonatal cord blood. Passive smoking in third trimester may lead to a decrease in birth weight. No evidence shows that leptin mediates the relationship between passive smoking and birth weight.
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Standardized training of specialists is an important part of medical education system. The training goal is to cultivate high-quality specialists with high clinical practice ability, teaching and scientific research ability. Based on the training practice of clinical, teaching and scientific research ability of the standardized training of cardiovascular specialists in Peking University Third Hospital, this paper discusses how to establish and improve the quality management system of cardiovascular specialist training, and introduces the training content, training methods, training organization and management, and training effect respectively, hoping to provide more practical basis for improving the quality of standardized training for cardiovascular specialists.
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The establishment of outcome-based or competency-based education is an important feature of today's curriculum plans. This paper reviews the development and application of outcome-based education (OBE) in medical education. Based on the concept of OBE, the curriculum framework system of Higher Medical Education is reformed and optimized, and the frameworks of course learning outcome, curriculum teaching theme and curriculum competency are redesigned and determined. Outcome-based curriculum reform reflects the requirements of global healthcare education for medical talents in the new era. Driven by the learning outcomes of postgraduates, the curriculum reform focuses on cultivating the postgraduates' recognition, understanding, analysis and research of the phenomena and problem-solving abilities in medical education by providing courses with different teaching topics, clear learning objectives and requirements. The systematic improvement of teaching quality is helpful to further promote the scientific research of medical education and the cultivation of professional talents in medical education management.
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Objective:To study the relationship between white matter injury (WMI) and brain maturity in preterm infants at full-term corrected gestational age (cGA).Methods:A retrospective study was performed in preterm infants [GA≤32 weeks or birth weight (BW) ≤1 500 g] admitted to the neonatal intensive care unit of the First Affiliated Hospital of Xi'an Jiaotong University from January 2017 to August 2018 and the Northwest Women and Children's Hospital from January 2017 to June 2017. The infants received conventional magnetic resonance imaging (MRI) at cGA 37~42 weeks. The infants were assigned into the WMI group and the control group according to the WMI scoring system, including the total maturation scores (TMS) and four sub-item scores.Results:A total of 118 premature infants were enrolled in this study (17 cases in the WMI group and 101 cases in the control group). The GA was (30.3±1.7) weeks, and BW was (1 356±268) g. The proportion of delayed TMS in the WMI group was significantly higher than the control group [58.8%(10/17) vs. 31.7%(32/101), P<0.05]. The TMS of the WMI group were significantly lower than the control group [(10.7±1.8) vs. (11.8±1.5), P<0.05]. The sub-item scores of TMS showed that the myelination [(2.8±0.6) vs. (3.1±0.4), P<0.05] and glial cell migration bands of the WMI group [(1.6±0.4) vs. (2.1±0.6), P=0.004] were significantly lower than the control group and no significant differences existed in cortical folding and involution of germinal matrix tissue scores between the two groups. Conclusions:The brain maturity of preterm infants with WMI is substantially delayed than those without WMI, including delayed myelination and delayed disappearance of glial cell migration bands.
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DNA damage response (DDR) is a highly conserved genome surveillance mechanism that preserves cell viability in the presence of chemotherapeutic drugs. Hence, small molecules that inhibit DDR are expected to enhance the anti-cancer effect of chemotherapy. Through a recent chemical library screen, we identified shikonin as an inhibitor that strongly suppressed DDR activated by various chemotherapeutic drugs in cancer cell lines derived from different origins. Mechanistically, shikonin inhibited the activation of ataxia telangiectasia mutated (ATM), and to a lesser degree ATM and RAD3-related (ATR), two master upstream regulators of the DDR signal, through inducing degradation of ATM and ATR-interacting protein (ATRIP), an obligate associating protein of ATR, respectively. As a result of DDR inhibition, shikonin enhanced the anti-cancer effect of chemotherapeutic drugs in both cell cultures and in mouse models. While degradation of ATRIP is proteasome dependent, that of ATM depends on caspase- and lysosome-, but not proteasome. Overexpression of ATM significantly mitigated DDR inhibition and cell death induced by shikonin and chemotherapeutic drugs. These novel findings reveal shikonin as a pan DDR inhibitor and identify ATM as a primary factor in determining the chemo sensitizing effect of shikonin. Our data may facilitate the development of shikonin and its derivatives as potential chemotherapy sensitizers through inducing ATM degradation.
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Recent studies have revealed great functional and structural heterogeneity in the ribbon-type synapses at the basolateral pole of the isopotential inner hair cell (IHC). This feature is believed to be critical for audition over a wide dynamic range, but whether the spatial gradient of ribbon morphology is fine-tuned in each IHC and how the mitochondrial network is organized to meet local energy demands of synaptic transmission remain unclear. By means of three-dimensional electron microscopy and artificial intelligence-based algorithms, we demonstrated the cell-wide structural quantification of ribbons and mitochondria in mature mid-cochlear IHCs of mice. We found that adjacent IHCs in staggered pairs differ substantially in cell body shape and ribbon morphology gradient as well as mitochondrial organization. Moreover, our analysis argues for a location-specific arrangement of correlated ribbon and mitochondrial function at the basolateral IHC pole.
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Animals , Mice , Artificial Intelligence , Cochlea/metabolism , Hair Cells, Auditory, Inner , Mitochondria , Synapses/metabolismABSTRACT
Objective@#To analyze anxiety and its influencing factors of medical college students during the epidemic of COVID-19, so as to provide theoretical basis for targeted mental health promotion.@*Methods@#Participants were selected through convenient sampling in 2 medical colleges, and general situation questionnaires, anxiety self rating scale(SAS), were csuected through questionnaire stars among to 6 276 medical college students anonymously through online platforms such as WeChat and QQ during the COVID-19 epidemic.@*Results@#SAS scores of medical students was(38.52±7.76), anxiety detection rate was 8.9%. Anxiety detection rate varied significantly by gender, the frequency of protection alerting by the counselor, college level, residence, self reported health status, confirmed cases in the community, personal attention, disinfection, perceived risk of infection,as well as panic in the outbreak of COVID-19 (all P <0.05). Multivariate Logistic analysis showed that undergraduate( OR = 1.25 ), high perceived risk of infection( OR =1.71); extreme panic ( OR =2.75) were associated with high detection rate of anxiety. Female students( OR =0.62), rural residents( OR =0.80), moderate health status( OR =0.06), in good health( OR =0.11), in excellent health( OR =0.30); know or don t know there were COVID-19 patients in their residential areas( OR =0.67), close attention to COVID-19 1-2 times/d( OR = 0.47 ), or frequently( OR =0.38); moderate inevitable disinfection( OR =0.53), few inevitable disinfection ( OR =0.32) were associated with low detection rate of anxiety.@*Conclusion@#During the epidemic of COVID-19, anxiety among the medical college students was high, which varies by gender and college level. Psychological adjustment, appropriate attention and positive attitude towards COVID-19 should be promoted among medical college students. School counsellors should pay more attention and care to students while providing COVID-19 information through various ways.
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The process of tourism economic development is accompanied by the consumption of energy and environment. It is of a big significance to measure the level of tourism economic development and regional eco-efficiency correctly to clarify the relationship between them, as it contributes to realizing the high-quality development of the tourism economy and the construction of "beautiful China". On the basis of the panel data of China's 30 provinces and cities from 2002 to 2016, the paper intends to evaluate the regional eco-efficiency and tourism economic development level by using the super-efficiency DEA model and the grey entropy weight method, and then construct spatial panel econometric model which is based on the previous data to deeply discuss the influence of tourism economy development on regional ecological efficiency and its spatial effect. The research shows that (1) regional ecological efficiency has significant spatial dependence and spatial aggregation characteristics. With the passing of time, this kind of positive spatial autocorrelation is gradually strengthened. (2) In the long-term development, tourism economic development and regional ecological efficiency show a more obvious "Kuznets curve" effect. (3) The "U"-curve relationship between urbanization, environmental regulation, and regional eco-efficiency was confirmed. (4) In the process of tourism economic transformation and development, industrial pollution control, environmental regulation, technological level, urbanization, and investment openness are the main factors that affect the improvement of ecological efficiency in the local region. (5) Tourism economic development and urbanization levels have different spatial spillover effects in different periods, while investment openness has obvious positive spillover effects.
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Economic Development , Urbanization , China , Cities , Efficiency , Environmental PollutionABSTRACT
The recent outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its rapid international spread pose a global health emergency. The trimeric spike (S) glycoprotein interacts with its receptor human ACE2 to mediate viral entry into host-cells. Here we present cryo-EM structures of an uncharacterized tightly closed SARS-CoV-2 S-trimer and the ACE2-bound-S-trimer at 2.7-Å and 3.8-Å-resolution, respectively. The tightly closed S-trimer with inactivated fusion peptide may represent the ground prefusion state. ACE2 binding to the up receptor-binding domain (RBD) within S-trimer triggers continuous swing-motions of ACE2-RBD, resulting in conformational dynamics of S1 subunits. Noteworthy, SARS-CoV-2 S-trimer appears much more sensitive to ACE2-receptor than SARS-CoV S-trimer in terms of receptor-triggered transformation from the closed prefusion state to the fusion-prone open state, potentially contributing to the superior infectivity of SARS-CoV-2. We defined the RBD T470-T478 loop and residue Y505 as viral determinants for specific recognition of SARS-CoV-2 RBD by ACE2, and provided structural basis of the spike D614G-mutation induced enhanced infectivity. Our findings offer a thorough picture on the mechanism of ACE2-induced conformational transitions of S-trimer from ground prefusion state towards postfusion state, thereby providing important information for development of vaccines and therapeutics aimed to block receptor binding.Competing Interest StatementThe authors have declared no competing interest.View Full Text
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Objective: To explore the early changes of left ventricular systolic function and synchrony in systemic lupus erythematosus (SLE) patients with longitudinal layer-specific strain imaging. Methods: Forty-two SLE patients (SLE group) and 30 healthy subjects (control group) were collected. Two-dimensional gray-scale moving images of three long axial sections of the left ventricular apex were stored, and the parameters of the longitudinal strain (LS) and peak strain dispersion (PSD) were obtained. The differences of these parameters were compared between groups. According to SLEDAI-2000 scoring system, the patients were divided into inactive phase (SLE-) subgroup and active phase (SLE+) subgroup, and the differences of related parameters were further analyzed. Results: Compared with control group, except apical segment, the LS of global and segmental three-layer myocardium decreased in SLE group (all P0.05). Conclusion: Longitudinal layer-specific strain imaging can be used to sensitively evaluate the subclinical left ventricular myocardial changes in SLE patients.
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Objective:To determine whether postoperative concurrent chemoradiotherapy (CCRT) improves the survival outcomes of cervical cancer patients with pelvic and/or para-aortic lymph node metastasis after radical surgery.Methods:Clinical data of 188 cervical cancer patients presenting with pelvic and/or para-aortic lymph node metastasis after radical surgery between February 2008 and November 2011 were retrospectively analyzed. The incidence of pelvic and/or para-aortic lymph node metastasis was confirmed by postoperative pathology. The clinical efficacy of CCRT was evaluated.Results:Recurrence/metastasis occurred in 46 patients. In the radiotherapy alone group, 4(57.1%) patients had recurrence/metastasis in the posterior peritoneum subgroup, 5(55.6%) in the iliac subgroup and 11(28.2%) in the pelvic non-iliac subgroup, respectively. In the CCRT group, there were 5(62.5%) cases of recurrence/metastasis in the posterior peritoneum subgroup, 5(25%) in the iliac subgroup and 16(15.2%) in the pelvic non-iliac subgroup, respectively. Compared with the radiotherapy alone, CCRT could significantly improve the 5-year overall survival (OS) rate of patients with pelvic without iliac lymph node metastasis or iliac lymph node metastasis (pelvic without iliac: 88.6% vs.76.9%, P=0.003; iliac: 80.0% vs.44.4%, P=0.041), whereas failed to improve the 5-year OS of patients with para-aortic lymph node metastasis (50.0% vs.42.9%, P=0.973). The location of lymph node metastasis and CCRT were the independent prognostic factors for OS (para-aortic vs. pelvic without iliac: hazard ratio[HR]=4.259, 95% CI=1.700-10.671, P=0.002; iliac vs. pelvic without iliac: HR=2.985, 95% CI=1.290-6.907, P=0.011; concurrent chemotherapy vs. radiotherapy alone: HR=0.439, 95% CI=0.218-0.885, P=0.021). Conclusions:CCRT can improve the survival of patients with pelvic lymph node metastasis, but it fails to enhance the survival rate of patients with para-aortic lymph node metastasis.
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The purpose of this study is to investigate the basic situation of self-regulated learning among clinical medical undergraduates in the stage of professional courses and construct a structural model suitable for them to carry out self-regulated learning . Zimmerman's self-regulated learning concept framework was determined as the theoretical basis of this study. A questionnaire survey was performed to identify five main dimensions affecting self-regulated learning including expression of learning intention, self-efficacy, adjustment of learning behavior, management of curriculum strategies, and adaption of learning environment, and then, Amos 24.0 software was used to construct the structural model and draw the conclusion that self-regulated learning in this group centers on the regulation of learning behavior, with learning intention and self-efficacy as sub-centers.
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Eradication the infection of Helicobacter pylori is essential for the treatment of gastrointestinal diseases such as gastrointestinal ulcer and gastric cancer.Because of the increased resistance rate of H.pylori to antibiotics,clarithromycin triple therapy is no longer the best treatment for H.pylori,especially in some parts of the country with over 20％ resistance to this antibiotic.Alternative therapies for eradicate of H.pylori have been proposed,including some new antibiotics or different combinations of classical antibiotics,which are used in regular clinical practice as a new and more effective treatment.Other treatments are antibiotic-related probiotics to treat the infection.The mechanism of which is not fully understood and needs further study.
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<p><b>OBJECTIVE</b>To report on the first case with chromosome 14q12 triplication involving the FOXG1 gene.</p><p><b>METHODS</b>The clinical, radiological and array-based comparative genomic hybridization (aCGH) data of a patient was analyzed, in addition with a literature review.</p><p><b>RESULTS</b>The 9-year-old girl has suffered from severe psychomotor delay, infantile spasms, severe mental retardation, absent language, autistic spectrum disorders, impaired ambulation, poor functional hand use and microcephaly, which were considered as manifestation of FOXG1 related diseases. Magnetic resonance imaging has documented heterotopic gray matter changes. aCGH showed a 1.9 Mb triplication in the 14q12 region, which involved the FOXG1 and a predicted gene 14orf23.</p><p><b>CONCLUSION</b>For patients with early-onset severe psychomotor retardation, epilepsy, microcephaly, severe cognitive impairment and encephalodysplasia, analysis of copy number variations and mutations of the FOXG1 gene is crucial for the diagnosis.</p>
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Child , Female , Humans , Autism Spectrum Disorder , Genetics , Chromosomes, Human, Pair 14 , Comparative Genomic Hybridization , DNA Copy Number Variations , Forkhead Transcription Factors , Genetics , Intellectual Disability , Genetics , Magnetic Resonance Imaging , Microcephaly , Genetics , Nerve Tissue Proteins , GeneticsABSTRACT
cyclic di-GMP (c-di-GMP) is a universal second messenger in bacterial cells. It regulates various biological processes such as biofilm development, pathogenicity, motility, exopolysaccharide (EPS) production and cell cycle. The second messenger exerts its function by binding to effectors, such as riboswitches and proteins. However, due to the diverse conformations of c-di-GMP, its effectors are hardly to be predicted by homology search. Identification of c-di-GMP effectors is the initial step to investigate its regulatory function in bacterial signal transduction, however, it remains to be a technically difficult task. Here we reviewed the mechanism of biofilm development controlled by c-di-GMP through binding to various types of protein effectors, and summarized the screening strategies, including genetics analysis, protein pull-down combined with LC/MS/MS identification, DRaCALA systematic screening and molecular docking-based prediction. We also summarized experimental methods for verifying protein-c-di-GMP interaction, including isothermal titration calorimetry, surface plasmon resonance, microscale thermophoresis etc. In addition, we discussed the advantages and disadvantages of these strategies and methods. The present review aims to facilitate the future investigations that are focused on regulatory role of novel c-di-GMP effectors.
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Polycystic ovary syndrome (PCOS) is an endocrine disorder with reproductive dysfunction and abnormal metabolic syndrome. However, its etiology is unknown yet. Androgen hypersecretion is one of the main features of PCOS. It has been found that PCOS has various effects on the offspring in reproductive, metabolic and nervous systems, including:increasing secretion of gonadotropin-releasing hormone and luteinizing hormone, ovarian morphological changes and abnormal secretion of sex hormones, leading to disorders of lipid and glucose metabolism, and increasing the risks of depression and autism. However, there is still lack of direct evidence, and more studies should be conducted on the underlying mechanism in future.
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Depression and anxiety is one of common mental illness that are being seriously harm to the physical and mental health of human being in recent years.Depression and anxiety are difficult to be well treated with a single and targeted drug,owing to its biological-psychological-social interaction pathogenic feature.Due to its own multicomponent characteristics,traditional Chinese medicine (TCM) compound Xiao-Yao (XY) powder can exert the antidepression and anxiety effects from multi-level,multi-link and multi-target.Based on previous studies on effect and mechanism of XY powder on anti-depression and anxiety of our group,we proposed that XY powder had two main characteristics when treating depression and anxiety,which were "two-way adjustment" and "multi-target,multisystem,multi-level".Additionally,to further clarify the pharmacodynamic material basis of XY powder,more importance is that we should depend on the variety of disciplinary research methods,focused on the TCM syndrome and the combination of disease and TCM syndrome,brought both disease evaluation and syndrome evaluation method,took the importance of gut-brain axis (GBA),and combined with the correlation between the formula and the syndrome.
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OBJECTIVE:To establish the method for simultaneous determination of paeoniflorin,amygdalin,ferulic acid and ligustrazine in Modified buying huanwu decoction.METHODS:RP-HPLC method was adopted.The determination was performed on YMC C18 column with the mobile phase consisted of acetonitrile-0.1％ phosphoric acid (gradient elution) at the flow rate of 1.0 mL/min.The detection wavelengths were set at 320 nm (femlic acid),230 nm (paeoniflorin),207 nm (amygdalin),280 nm (ligustrazine).The column temperature was 30 ℃,and sample size was 10 μL.RESULTS:The linear ranges of paeoniflorin,amygdalin,femlic acid and ligustrazine were 0.191 2-1.912 μg/mL (r=0.999 6),0.117 4-1.174 μg/mL (r=0.999 6),0.011 5-0.115 μg/mL (r=0.999 8) and 0.001 66-0.016 6 μg/mL(r=0.999 7),respectively.The limits of quantitation were 1.912,1.174,0.115,0.016 6 μg/mL,and the limits of detection were 0.25,0.40,0.05,0.008 5 μg/mL,respectively.RSDs of precision,stability and reproducible tests were all lower than 2.0％.The recoveries were 96.9％-100.3％ (RSD=1.3％,n=6),95.1％-100.3％ (RSD=2.2％,n=6),95.3％-100.2％ (RSD=2.0％,n=6)and 97.0％-100.0％ (RSD=1.3％,n=6).CONCLUSIONS:The method is reliable,simple and accurate,and is suitable for simultaneous determination of paeoniflorin,amygdalin,ferulic acid and ligustrazine in Modified buyang huanwu decoction.
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OBJECTIVE:To establish the method for simultaneous determination of paeoniflorin,amygdalin,ferulic acid and ligustrazine in Modified buying huanwu decoction.METHODS:RP-HPLC method was adopted.The determination was performed on YMC C18 column with the mobile phase consisted of acetonitrile-0.1％ phosphoric acid (gradient elution) at the flow rate of 1.0 mL/min.The detection wavelengths were set at 320 nm (femlic acid),230 nm (paeoniflorin),207 nm (amygdalin),280 nm (ligustrazine).The column temperature was 30 ℃,and sample size was 10 μL.RESULTS:The linear ranges of paeoniflorin,amygdalin,femlic acid and ligustrazine were 0.191 2-1.912 μg/mL (r=0.999 6),0.117 4-1.174 μg/mL (r=0.999 6),0.011 5-0.115 μg/mL (r=0.999 8) and 0.001 66-0.016 6 μg/mL(r=0.999 7),respectively.The limits of quantitation were 1.912,1.174,0.115,0.016 6 μg/mL,and the limits of detection were 0.25,0.40,0.05,0.008 5 μg/mL,respectively.RSDs of precision,stability and reproducible tests were all lower than 2.0％.The recoveries were 96.9％-100.3％ (RSD=1.3％,n=6),95.1％-100.3％ (RSD=2.2％,n=6),95.3％-100.2％ (RSD=2.0％,n=6)and 97.0％-100.0％ (RSD=1.3％,n=6).CONCLUSIONS:The method is reliable,simple and accurate,and is suitable for simultaneous determination of paeoniflorin,amygdalin,ferulic acid and ligustrazine in Modified buyang huanwu decoction.
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Objective To explore the adaptive modulation of brain in structure and function when moving to high altitude areas based on voxel-based morphometry (VBM),amplitude of low frequency fluctuation (ALFF)and regional homogeneity (ReHo) method.Methods Resting-state functional magnetic resonance imaging (fMRI)of brain was respectively performed in 1 9 normal adults who moved to high altitude areas within a week,and they have matched age and education level.The subj ects were performed the same scanning after one year.The VBM,ALFF and ReHo methods were adopted to analyze the functional MRI data.Results There were no significant differences in brain structure between the two groups.There were significant differences in brain function in resting state.Subj ects staying in high altitude areas for one year had increased ALFF in left middle frontal gyrus,decreased ALFF in right lingual gyrus(P<0.01),increased ReHo in the left orbital frontal gyrus,and decreased ReHo in right cuneus and right superior parietal gyrus(P<0.05).Conclusion There are significant changes in brain function of normal adult after stayed in high altitude for one year,which might be associated with long-term chronic hypoxia.
