[Pollution Characteristics, Source, and Health Risk Assessment of Metal Elements in PM2.5 Between Winter and Spring in Zhengzhou].

A total of 18 metal elements in ambient PM2.5 in Zhengzhou were continuously determined using an online heavy metal observation instrument in January and April, 2021, and the changes in element concentrations were analyzed. Metal elements were traced via enrichment factors, positive matrix factorization (PMF), and a characteristic radar chart. The US EPA health risk assessment model was used to assess the health risks of heavy metals, and the backward trajectory method and the concentration-weighted trajectory (CWT) method were used to evaluate the potential source regions of health risks. The results showed that the element concentrations were higher in spring, and the sum of Fe, Ca, Si, and Al concentrations accounted for 89.8% and 87.5% of the total element concentrations in winter and spring, respectively. Cd was enriched significantly, which was related to human activities. The concentrations of Pb, Se, Zn, Ni, Sb, and K in winter and Cr, Ni, Fe, Mn, V, Ba, Ca, K, Si, and Al in spring increased with the increasing pollution level. The results of PMF and the characteristic radar chart showed that the main sources of metal elements in winter and spring were industry, crust, motor vehicles, and mixed combustion, with industry and mixed combustion pollution occurring more often in winter and crust pollution occurring more often in spring. Significant non-carcinogenic risks existed in both winter and spring with more severe health risks in winter, and Mn caused significant non-carcinogenic risks. The health risks in winter were mainly influenced by Zhengzhou and surrounding cities and long-distance transport in the northwest, and the health risks in spring were mainly influenced by Zhengzhou and surrounding cities.

Circadian disruption during fetal development promotes pathological cardiac remodeling in male mice.

Disruption of circadian rhythms during fetal development may predispose mice to developing heart disease later in life. Here, we report that male, but not female, mice that had experienced chronic circadian disturbance (CCD) in utero were more susceptible to pathological cardiac remodeling compared with mice that had developed under normal intrauterine conditions. CCD-treated males showed ventricular chamber dilatation, enhanced myocardial fibrosis, decreased contractility, higher rates of induced tachyarrhythmia, and elevated expression of biomarkers for heart failure and myocardial remodeling. In utero CCD exposure also triggered sex-dependent changes in cardiac gene expression, including upregulation of the secretoglobin gene, Scgb1a1, in males. Importantly, cardiac overexpression of Scgb1a1 was sufficient to induce myocardial hypertrophy in otherwise naive male mice. Our findings reveal that in utero CCD exposure predisposes male mice to pathological remodeling of the heart later in life, likely as a consequence of SCGB1A1 upregulation.

Clinical and immunological characteristics of acute viral infection-related encephalopathy / 中华实用儿科临床杂志

Objective:To analyze the clinical and immunological characteristics of children with acute viral infection-related encephalopathy.Methods:Case-control study.A retrospective analysis was conducted on the clinical data of children diagnosed with acute viral infection-related encephalopathy during hospitalization at the Children′s Hospital, Capital Institute of Pediatrics from January 2020 to January 2023.According to the last follow-up modified Rankin scale (mRS) score, these children were divided into a good prognosis group (mRS score ≤2) and a poor prognosis group (mRS score >2), and the clinical and immunological characteristics of the children with different prognoses were analyzed.The binary Logistic regression was used to analyze the risk factors for poor prognosis.Results:A total of 28 children with acute viral infection-related encephalopathy aged 4 months to 11 years were included.There were 16 males (57%) and 12 females (43%). Among the preinfection viruses, there were 16 children of Corona virus disease 2019, 8 children of influenza A virus, 3 children of influenza B virus, and 1 child of norovirus.Among them, there were 21 children with acute necrotizing encephalopathy, 4 children with acute encephalopathy with biphasic seizures and late reduced diffusion, 2 children with mild encephalitis with a reversible splenial lesion, and 1 child with hemorrhagic shock and encephalopathy syndrome.Among the first symptoms, 24 children (85.7%) had consciousness disorders, 23 children (82.1%) had seizures, 17 children (60.7%) had speech disorders, 11 children (39.3%) had involuntary movements, and 10 children (35.7%) had abnormal mental behavior.For the site of lesion, the cranial nuclear magnetic resonance imaging revealed 17 in the thalamus, 10 in the brainstem, 9 in the basal ganglia, 8 in the cerebellar hemisphere, and 4 in the corpus callosum.In the last follow-up evaluation, 17 children had a mRS score of >2, and 11 children had a mRS score of ≤2.Univariate analysis showed that disturbance of consciousness, seizure cluster, brain stem lesion, absolute value of serum T lymphocytes, cerebrospinal fluid(CSF) protein, CSF cytokines [interleukin(IL)-1β, IL-6 and IL-8]were higher in the poor prognosis group than those in the good prognosis group.Multivariate Logistic regression analysis indicated that brain stem disease, CSF IL-1β and T lymphocyte absolute number were independent risk factors for poor prognosis.Conclusions:Brain stem lesions, cerebrospinal fluid IL-1β and the absolute number of T lymphocytes have predictive value for the prognosis of acute viral infection-associated encephalopathy.The more severe the conditions, the lower the T lymphocytes, and the higher the cytokines in some cerebrospinal fluid.

SARS-CoV-2 NSP13 interacts with host IRF3, blocking antiviral immune responses.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an unprecedented threat to human health since late 2019. Notably, the progression of the disease is associated with impaired antiviral interferon (IFN) responses. Although multiple viral proteins were identified as potential IFN antagonists, the underlying molecular mechanisms remain to be fully elucidated. In this study, we firstly demonstrate that SARS-CoV-2 NSP13 protein robustly antagonizes IFN response induced by the constitutively active form of transcription factor IRF3 (IRF3/5D). This induction of IFN response by IRF3/5D is independent of the upstream kinase, TBK1, a previously reported NSP13 target, thus indicating that NSP13 can act at the level of IRF3 to antagonize IFN production. Consistently, NSP13 exhibits a specific, TBK1-independent interaction with IRF3, which, moreover, is much stronger than that of NSP13 with TBK1. Furthermore, the NSP13-IRF3 interaction was shown to occur between the NSP13 1B domain and IRF3 IRF association domain (IAD). In agreement with the strong targeting of IRF3 by NSP13, we then found that NSP13 blocks IRF3-directed signal transduction and antiviral gene expression, counteracting IRF3-driven anti-SARS-CoV-2 activity. These data suggest that IRF3 is likely to be a major target of NSP13 in antagonizing antiviral IFN responses and provide new insights into the SARS-CoV-2-host interactions that lead to viral immune evasion.

The mediating effect of math self-efficacy on the relationship between parenting style and math anxiety.

The present study aims to investigate the associations among math self-efficacy, parenting style, and math anxiety in primary school children. The sample comprised 400 participants, aged between 10 and 11 years old, from an elementary school in China. Participants completed three self-reported questionnaires on math anxiety, parenting styles and math self-efficacy. The results revealed that rejection was strongly and positively correlated with math anxiety, while emotional warmth was negatively related to math anxiety. Interestingly, math anxiety was found to be related to rejection, with math self-efficacy playing a mediating role in this relationship. Conversely, math self-efficacy played a mediating role in the relationship between parenting styles and math anxiety, while over protection exhibited no significant correlation with math anxiety. The study also showed that gender differences existed in the level of math anxiety and math self-efficacy, with boys exhibiting lower math anxiety and higher math self-efficacy than girls. These results provide important insights into the development and treatment of math anxiety in primary school children. Specifically, parents and educators should focus on enhancing children's math self-efficacy beliefs, while adopting a parenting style characterized by emotional warmth and low levels of rejection.

Molecular characterization and antimicrobial susceptibility of human Brucella in Northeast China.

Introduction: Northeast China has always been an area with severe brucellosis prevalence. This study will identify Brucella in Northeast China and test its resistance to antibiotics, in order to clarify its resistance mechanism. Brucella is a widespread and highly pathogenic bacteria that poses serious threats to public health and animal husbandry. Methods: In this study, 61 Brucella isolates were identified by abortus-melitensis-ovis-suis polymerase chain reaction (AMOS-PCR) for biotypes and epidemic potential was clarified by multi-locus sequence analysis. Whole-genome sequencing (WGS) was performed and the antibiotic susceptibility of the Brucella strains against 13 antibiotics was detected with the use of E-test strips. Results: The results showed that all of the isolates were Brucella melitensis ST8, group CC4 with little genetic variation and obvious geographical characteristics. All 61 Brucella isolates were sensitive to doxycycline, tetracycline, minocycline, levofloxacin, ciprofloxacin, gentamicin, and streptomycin, while 24.6%, 86.9%, 65.6%, 27.9%, 3.3%, and 1.6% were resistant to rifampin, azithromycin, cefepime, cefoperazone/sulbactam, cefotaxime, and meperidine/sulfamethoxazole, respectively. This is the first report of cephalosporin-resistant B. melitensis in China. The WGS results indicated that about 60% of the antibiotic resistance genes were associated with efflux pumps (mainly the resistance nodulation division family). Discussion: Brucellosis is usually treated with antibiotics for several months, which can easily lead to the emergence of antibiotic resistance. To ensure the effectiveness and safety of antibiotics for treatment of brucellosis, continuous surveillance of antibiotic susceptibility is especially important.

Efficacy and safety of selegiline for the treatment of Parkinson's disease: A systematic review and meta-analysis.

Background: Drug efficacy generally varies with different durations. There is no systematic review analyzing the effect of selegiline for Parkinson's disease (PD) on different treatment duration. This study aims to analyze how the efficacy and safety of selegiline changes for PD over time. Methods: PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure and Wanfang Database were systematically retrieved for randomized controlled trials (RCTs) and observational studies of selegiline for PD. The search period was from inception to January 18th, 2022. The efficacy outcomes were measured by the mean change from baseline in the total and sub Unified Parkinson's Disease Rating Scale (UPDRS), Hamilton Depression Rating Scale (HAMD) and Webster Rating Scale (WRS) scores. The safety outcomes were measured by the proportion of participants having any adverse events overall and that in different system organ classes. Results: Among the 3,786 studies obtained, 27 RCTs and 11 observational studies met the inclusion criteria. Twenty-three studies reported an outcome which was also reported in at least one other study, and were included in meta-analyses. Compared with placebo, selegiline was found with a stronger reduction of total UPDRS score with increasing treatment duration [mean difference and 95% CIs in 1 month: -3.56 (-6.67, -0.45); 3 months: -3.32 (-3.75, -2.89); 6 months: -7.46 (-12.60, -2.32); 12 months: -5.07 (-6.74, -3.41); 48 months: -8.78 (-13.75, -3.80); 60 months: -11.06 (-16.19, -5.94)]. A similar trend was also found from the point estimates in UPDRS I, II, III, HAMD and WRS score. The results of observational studies on efficacy were not entirely consistent. As for safety, compared with placebo, selegiline had higher risk of incurring any adverse events [rate: 54.7% vs. 62.1%; odd ratio and 95% CIs: 1.58 (1.02, 2.44)], with the excess adverse events mainly manifested as neuropsychiatric disorders [26.7% vs. 31.6%; 1.36 (1.06, 1.75)] and no significant change over time. The statistically difference in overall adverse event between selegiline and active controls was not found. Conclusion: Selegiline was effective in improving total UPDRS score with increasing treatment duration, and had a higher risk of incurring adverse events, especially the adverse events in the neuropsychiatric system. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: PROSPERO CRD42021233145.

Subcellular distribution, chemical forms of cadmium and rhizosphere microbial community in the process of cadmium hyperaccumulation in duckweed.

Duckweed is a newly reported Cd hyperaccumulator that grow rapidly; however, little is known about its tolerance and detoxification mechanisms. In this study, we investigated the tissue, subcellular, and chemical form distribution of the Cd in duckweed and studied the influences of Cd on duckweed growth, ultrastructure, and rhizosphere microbial community. The results showed that Cd could negatively affect the growth of duckweed and shorten the root length. More Cd accumulated in the roots than in the leaves, and Cd was transferred from the roots to the leaves with time. During 12-24 h, Cd mainly existed in the cell wall fraction (2.05 %-95.52 %) and the organelle fraction (5.03 %-97.80 %), followed the soluble fraction (0.14 %-16.98 %). Over time, the proportion of Cd in the organelles increased (46.64 %-92.83 %), exceeding that in the cell wall (6.79 %-66.23 %), which indicated that duckweed detoxification mechanism may be related to the retention of cell wall and vacuole. The main chemical form of Cd was the NaCl-extracted state (30.15 %-88.66 %), which was integrated with pectate and protein. With increasing stress concentration and time, the proportion of the HCl-extracted state and HAc-extracted state increased, and they were low-toxic Cd oxalate and Cd phosphate, respectively. Cd damaged the ultrastructure of cells such as chloroplasts and mitochondria and inhibited the diversity of microbial communities in the duckweed rhizosphere; however, the dominant populations that could tolerate heavy metals increased. It was speculated that duckweed distributed Cd in a less toxic chemical form in a less active location, mainly through retention in the root cell wall and sequestration in the leaf vacuoles, and is dynamically adjusted. The rhizosphere microbial communities tolerate heavy metals may also be one of the mechanisms by which duckweed can tolerate Cd. This study revealed the mechanism of duckweed tolerance and detoxification of Cd at the molecular level and provides a theoretical basis for further development of duckweed.

Influences of the copy number of SMN2 and transcript level of fl-SMN2 on the phenotype and survival of spinal muscular atrophy / 中华实用儿科临床杂志

Objective:To explore the distribution of the copy number of survival motor neuron gene 2 ( SMN2) and the transcript level of the full-length SMN2 ( fl-SMN2) transcript level in patients with type 1-3 spinal muscular atrophy (SMA), and to evaluate their influences on disease severity, progression, and prognosis. Methods:It was a retrospective study involving 78 therapy-naive SMA patients with SMN1 gene homozygous deletion who were diagnosed and treated in the Capital Institute of Pediatrics from January 2019 to December 2021.Cross-sectional clinical data, including age at onset, motor milestones, and complications were recorded.They were followed up for monitoring motor function degeneration and survival.The copy number of SMN2 and the transcript level of fl-SMN2 were detected.Differences between groups were compared by the Student′s t-test or One- Way ANOVA or Chi- square test.Kaplan-Meier analysis was used for survival analysis, and Kendall′ s tau- c was performed to assess the correlation of these two biomarkers with SMA phenotypes, age at onset, motor milestones, and survival. Results:Of the 78 SMA patients, there were 17 cases (21.8%) of type 1, 34 cases(43.6%) of type 2, and 27 cases(34.6%) of type 3.Seven cases(41.2%) type 1 SMA patients died, with a median survival time of 11 months, and no deaths were observed in type 2 and type 3 SMA patients.There was a significant difference in the median age at onset among SMA patients with 2, 3, and 4 copies of SMN2 (1.8, 12.0, and 24.0 months, respectively; F=4.943, P=0.01). The mean transcript level of fl-SMN2 in type 1, 2 and 3 SMA patients were 196.25±68.79, 331.21±108.79 and 455.69±122.27, respectively ( F=37.154, P<0.001). The survival rate of SMA with 2 SMN2 copies at 1, 2, and 5 years were 50.5%, 0, and 0, respectively, and their median survival age was 7 months.The survival rate of SMA with 3 and 4 SMN2 copies at 5 years were 97.4% and 100.0%, respectively.Moreover, a negative correlation was observed between the transcript level of fl-SMN2 and phenotype severity ( Kendall′ s tau- c=-0.444, P<0.001), and the transcript level of fl-SMN2 of the survival group was much higher than that of the death group (342.93±125.74 vs.212.14±92.31). More copies of SMN2 and higher transcript level of fl- SMN2 indicated more motor function acquisitions (head control, sitting and walking) ( P<0.001). In addition, there was a significant difference in the transcription level of fl-SMN2 between the undegenerated group and the degenerated group in sitting and standing ( F=5.432, P=0.023 and F=4.315, P=0.047, respectively). Conclusions:Both the copy number of SMN2 and the transcript level of fl-SMN2 are correlated with SMA severity, survival, and motor milestones, serving as valuable biomarkers for evaluating phenotypic severity of SMA.The transcript level of fl-SMN2 s may play an important role in the degeneration of sitting and standing.

Research Status and Trend of Devices for Treating Advanced Heart Failure / 中国医学科学院学报

Heart failure (HF),a chronic progressive disease,is a global health problem and the leading cause of deaths in the global population.The pathophysiological abnormalities of HF mainly include abnormal cardiac structure (myocardium and valves),disturbance of electrophysiological activities,and weakened myocardial contractility.In addition to drug therapy and heart transplantation,interventional therapies can be employed for advanced-stage HF,including transcatheter interventions and mechanical circulatory assist devices.This article introduces the devices used for advanced HF that have been marketed or certified as innovative or breakthrough devices around the world and summarizes the research status and prospects the trend in this field.As diversified combinations of HF devices are used for the treatment of advanced HF,considerations regarding individualized HF therapy,risk-benefit evaluation on device design,medical insurance payment,post-market supervision system,and protection of intellectual property rights of high-end technology are needed,which will boost the development of the technology and industry and benefit the patients.

Investigation and analysis of airborne allergenic pollen in 4 districts and 5 counties of Hohhot City / 中华预防医学杂志

Objective: To investigate the species, concentration and seasonal trends of main airborne allergenic pollen in 4 districts and 5 counties of Hohhot City. Methods: The Department of allergy, Beijing Shijitan Hospital Affiliated to Capital Medical University conducted a cross-sectional study about monitoring the airborne allergenic pollen from August 1, 2021 to July 31, 2022 by the gravitational method in 4 districts and 5 counties of Hohhot City, which include Yuquan District, Xincheng District, Huimin District, Saihan District, Tuoketuo County, Helingeer County, Tumotezuoqi County, Wuchuan County and Qingshuihe County. Daily pollens were counted and identified by optical microscopy, and the data were analyzed. Results: The airborne allergenic pollen was collected every month all year round in 4 districts and 5 counties of Hohhot city. Through the whole year of the total quantity of pollens ranged from 24 850 to 50 154 grains per 1 000 mm2 and two peaks of pollen concentration in air were observed,which happened in spring (from March to May) and in summer and autumn (from July to September). In spring, the main pollens were tree pollens, which principally distributed in Populus pollen (18.29%), Ulmus pollen (8.36%), Pinus pollen (6.20%), Cupressaceae pollen (5.23%), Betulaceae pollen (2.73%), Salix pollen (1.80%) and Quercus pollen (1.16%). In summer and autumn, the main pollens were weed pollens, which mainly included Artemisia pollen (42.73%), Chenopodiaceae pollen or Amaranthaceae pollen (7.46%), Poaceae pollen (2.26%), Humulus pollen or Cannabis pollen (0.60%). Conclusion: There were two peaks of main airborne allergenic pollen in 4 districts and 5 counties of Hohhot City. In the spring peak of pollen, the main airborne pollens were tree pollens. In the summer and autumn peak of pollen, the main airborne pollens were weed pollens. The Artemisia pollen was the most major airborne pollen in this area.

Investigation and analysis of airborne allergenic pollen in 4 districts and 5 counties of Hohhot City / 中华预防医学杂志

Objective: To investigate the species, concentration and seasonal trends of main airborne allergenic pollen in 4 districts and 5 counties of Hohhot City. Methods: The Department of allergy, Beijing Shijitan Hospital Affiliated to Capital Medical University conducted a cross-sectional study about monitoring the airborne allergenic pollen from August 1, 2021 to July 31, 2022 by the gravitational method in 4 districts and 5 counties of Hohhot City, which include Yuquan District, Xincheng District, Huimin District, Saihan District, Tuoketuo County, Helingeer County, Tumotezuoqi County, Wuchuan County and Qingshuihe County. Daily pollens were counted and identified by optical microscopy, and the data were analyzed. Results: The airborne allergenic pollen was collected every month all year round in 4 districts and 5 counties of Hohhot city. Through the whole year of the total quantity of pollens ranged from 24 850 to 50 154 grains per 1 000 mm2 and two peaks of pollen concentration in air were observed,which happened in spring (from March to May) and in summer and autumn (from July to September). In spring, the main pollens were tree pollens, which principally distributed in Populus pollen (18.29%), Ulmus pollen (8.36%), Pinus pollen (6.20%), Cupressaceae pollen (5.23%), Betulaceae pollen (2.73%), Salix pollen (1.80%) and Quercus pollen (1.16%). In summer and autumn, the main pollens were weed pollens, which mainly included Artemisia pollen (42.73%), Chenopodiaceae pollen or Amaranthaceae pollen (7.46%), Poaceae pollen (2.26%), Humulus pollen or Cannabis pollen (0.60%). Conclusion: There were two peaks of main airborne allergenic pollen in 4 districts and 5 counties of Hohhot City. In the spring peak of pollen, the main airborne pollens were tree pollens. In the summer and autumn peak of pollen, the main airborne pollens were weed pollens. The Artemisia pollen was the most major airborne pollen in this area.

Is compromised intestinal barrier integrity responsible for the poor prognosis in critically ill patients with pre-existing hyperglycemia?

BACKGROUND: Compromised intestinal barrier integrity can be independently driven by hyperglycemia, and both hyperglycemia and intestinal barrier injury are associated with poor prognosis in critical illness. This study investigated the intestinal barrier biomarkers in critically ill patients, to explore the role of compromised intestinal barrier integrity on the prognosis of critically ill patients with pre-existing hyperglycemia. METHODS: This was a retrospective observational study. The relationships between intestinal barrier biomarkers and glycated hemoglobin A1c (HbA1c), fasting blood glucose (FBG), indicators of clinical characteristics, disease severity, and prognosis in critically ill patients were investigated. Then the metrics mentioned above were compared between survivors and non-survivors, the risk factors of 90-day mortality were investigated by logistic regression analysis. Further, patients were divided into HbA1c < 6.5% Group and HbA1c ≥ 6.5% Group, metrics mentioned above were compared between these two groups. RESULTS: A total of 109 patients with critical illness were included in the study. D-lactate and lipopolysaccharide (LPS) were associated with sequential organ failure assessment (SOFA) score and 90-day mortality. LPS was an independent risk factor of 90-day mortality. DAO, NEU (neutrophil) proportion, temperature, lactate were lower in HbA1c ≥ 6.5% Group while D-lactate, LPS, indicators of disease severity and prognosis showed no statistical difference between HbA1c < 6.5% Group and HbA1c ≥ 6.5% Group. CONCLUSIONS: Intestinal barrier integrity is associated with the disease severity and prognosis in critical illness. Compromised intestinal barrier integrity might be responsible for the poor prognosis in critically ill patients with pre-existing hyperglycemia.

Anti-Hyperglycemic Agents in the Adjuvant Treatment of Sepsis: Improving Intestinal Barrier Function.

Intestinal barrier injury and hyperglycemia are common in patients with sepsis. Bacteria translocation and systemic inflammatory response caused by intestinal barrier injury play a significant role in sepsis occurrence and deterioration, while hyperglycemia is linked to adverse outcomes in sepsis. Previous studies have shown that hyperglycemia is an independent risk factor for intestinal barrier injury. Concurrently, increasing evidence has indicated that some anti-hyperglycemic agents not only improve intestinal barrier function but are also beneficial in managing sepsis-induced organ dysfunction. Therefore, we assume that these agents can block or reduce the severity of sepsis by improving intestinal barrier function. Accordingly, we explicated the connection between sepsis, intestinal barrier, and hyperglycemia, overviewed the evidence on improving intestinal barrier function and alleviating sepsis-induced organ dysfunction by anti-hyperglycemic agents (eg, metformin, peroxisome proliferators activated receptor-γ agonists, berberine, and curcumin), and summarized some common characteristics of these agents to provide a new perspective in the adjuvant treatment of sepsis.

Recent Advance of Stainless Steel Used In Non-active Surgical Implantable Medical Device and Regulatory Perspective / 中国医疗器械杂志

Stainless steel has been widely used in non-active surgical implantable medical device of cardiovascular, orthopedics, dental and ophthalmology. In this paper, we mainly focused on development of stainless steel, as well as the material-related standard evolution. We further summarized the recent advancement of stainless steel use in surgical implantable medical device. Insight and regulatory perspective has been further demonstrated.

Spindle cell hemangioma: a clinicopathological and molecular analysis of eight cases / 中华病理学杂志

Objective: To investigate the clinicopathological and genetic characteristics of spindle cell hemangioma (SCH). Methods: The clinical, morphological and immunohistochemical features of 8 SCHs diagnosed from January 2013 to September 2021 in West China Hospital, Sichuan University, Chengdu, China were retrospectively analyzed. Hotspot mutations for IDH1 codon 132 and IDH2 codon 172 were tested in 4 SCHs and 29 other non-SCH lesions using Sanger sequencing. Results: The 8 cases occurred in patients with a wide age range, from neonate to 46 years (mean 28 years, median 32 years). Both genders were equally affected. The course of the disease spanned from half a year to 31 years. Two SCHs were recurrent tumors. All tumors involved the distal extremities (4 of foot, 2 of ankle and 2 of hand). Six cases were presented as a single lesion and 2 cases as multiple lesions. The tumor diameters were 1-5 cm. All the 8 SCHs were typically composed of cavernous vascular space and solid components consisting of slit-like vessels, spindle cells and epithelioid endothelial cells which often exhibited cytoplasmic vacuolation. These two alternating components and the vacuolated epithelioid endothelial cells were the distinctive diagnostic clues for SCH. Vascular endothelial cells including epithelioid cells in the solid areas expressed CD31 (8/8), ERG (4/4), CD34 (5/8) and D2-40 (2/3). The spindle cells expressed SMA (8/8). Neither endothelial cells nor spindle cells expressed HHV8 (0/7), Desmin (0/5) or S-100 (0/3). Mutations were revealed in 2 SCHs, with IDH1 mutation (p.R132C) and IDH2 mutation (p.R172G), respectively. The IDH1/2 gene hotspot mutations were not found in the remaining 2 SCHs or the other 29 non-SCH lesions. Simple excisions were performed for 7 cases, and partial resection for 1 case. Follow-up information was obtained in 6 cases, with follow-up time ranging from 5 to 90 months (average, 46 months). No metastasis occurred in the 6 cases. No recurrence occurred in cases treated with simple excision. The residual lesions of the patient who received partial resection were stable. Conclusions: SCH is rare and should be differentiated from a variety of benign and malignant vascular lesions. An accurate diagnosis of SCH is clinically important and can be achieved by combining clinical information and typical pathological presentation. IDH1/2 gene hotspot mutations are specific to SCH in vascular lesions. Genetic detection is helpful in the diagnosis of challenging cases.

Silk fibroin/collagen composite hydrogels with different matrix stiffness influence the growth and phenotype of human mammary epithelial cells / 生理学报

Extracellular matrix (ECM) stiffness is closely related to the physiological and pathological states of breast tissue. The current study was aimed to investigate the effect of silk fibroin/collagen composite hydrogels with adjustable matrix stiffness on the growth and phenotype of normal breast epithelial cells. In this study, the enzymatic reaction of horseradish peroxidase (HRP) with hydrogen peroxide (H2O2) was used to change the degree of cross-linking of the silk fibroin solution. The rotational rheometer was used to characterize the composite hydrogel's biomechanical properties. Human normal mammary epithelial cell line MCF-10A were inoculated into composite hydrogels with various stiffness (19.10-4 932.36 Pa) to construct a three dimensional (3D) culture system of mammary epithelial cells. The CCK-8 assay was applied to detect the cell proliferation rate and active states in each group. Hematoxylin-Eosin (HE) staining and whole-mount magenta staining were used for histological evaluation of cell morphology and distribution. The results showed that with the increase of matrix stiffness, MCF-10A cells exhibited inhibited proliferation rate, decreased formation of acinus structures and increased branching structures. Meanwhile, with the increase of matrix stiffness, the polarity of MCF-10A cells was impeded. And the increase of matrix stiffness up-regulated the expression levels of mmp-2, mmp-3, and mmp-9 in MCF-10A cells. Among the genes related to epithelial-mesenchymal transition (EMT), the expression level of the epithelial marker gene E-cadherin was significantly down-regulated, while the interstitial cell marker gene Vimentin was up-regulated, and the expression levels of Snail, Wnt5b and Integrin β1 in the Wnt pathway were up-regulated. These results suggest that the silk fibroin/collagen composite hydrogels with adjustable matrix stiffness regulates the proliferation and the phenotype of MCF-10A cells. The effects of increased matrix stiffness may be closely related to the changes of the polar structures and function of MCF-10A cells, as well as the occurrence of ECM-remodeling and EMT.

Does three cycles of neoadjuvant chemotherapy prior to concurrent chemoradiotherapy provide benefits for all childhood patients with locoregionally advanced nasopharyngeal carcinoma?

BACKGROUND: Adding neoadjuvant chemotherapy (NAC) to concurrent chemoradiotherapy (CCRT) is the main strategy in treatment of children and adolescents with locoregionally advanced nasopharyngeal carcinoma (CA-LANPC). Yet, an optimal number of NAC cycles remains unknown. We aimed to optimize the NAC cycle and potentially contribute to clinical decision making for the individual treatment of CA-LANPC. PATIENTS AND METHODS: Utilizing an NPC-specific database through an acknowledged big-data information system at our center, we identified 143 CA-LANPC treated with NAC followed by CCRT between September 2007 through April 2018. Recursive partitioning analysis (RPA) was performed to categorize the patients and predict disease-free survival (DFS). The clinical benefits of NAC cycles (two cycles vs three cycles) were assessed in each risk group. RESULTS: Independent factors derived from multivariable analysis to predict DFS were T stage (T1-3 vs T4) and plasma Epstein-Barr virus (EBV) DNA (< 4000 vs ≥ 4000 copies/mL) for risk stratification. Consequently, 87 (61%) participants were classified as low-risk group (T1-3 with low or high EBV DNA, and T4 with low EBV DNA) and the other 56 patients (39%) were classified as a high-risk group (T4 with high EBV DNA) through RPA, and corresponding 5-year DFS rates of 91.9% and 71.2%, respectively (p = 0.001). Among the high-risk group, patients receiving three cycles of NAC had statistically significant improvement in 5-year DFS over those who received two cycles of NAC (86.7% vs 59.1%; p = 0.020), while the survival benefit of three cycles NAC for low-risk groups were not observed (94.7% vs 89.7%; p = 0.652). CONCLUSIONS: We found three cycles of NAC with CCRT was a positive prognostic indicator for improved DFS for the high-risk group among CA-LANPC. However, whether low-risk patients could benefit from three cycles NAC needs further study.

Preoperative prediction of gastrointestinal stromal tumors with high Ki-67 proliferation index based on CT features.

BACKGROUND: To determine whether preoperative computed tomography (CT) features can be used for the prediction of gastrointestinal stromal tumors (GISTs) with a high Ki-67 proliferation index (Ki-67 PI). METHODS: A total of 198 patients with surgically and pathologically proven GISTs were retrospectively included. All GISTs were divided into a low Ki-67 PI group (<10%) and a high Ki-67 PI group (≥10%). All imaging features were blindly interpreted by two radiologists. Receiver operating characteristic (ROC) curve analyses were conducted to evaluate the predictive performance of the imaging features. RESULTS: Imaging features were found to be significantly different between the low and the high Ki-67 PI groups (P<0.05). Wall thickness of necrosis showed the highest predictive ability, with an area under the curve (AUC) of 0.838 [95% confidence interval (CI): 0.627-0.957], followed by necrosis, necrosis degree, hyperenhancement of the overlying mucosa (HYOM), and long diameter (LD) (AUC >0.7, P<0.05). HYOM was the strongest predictive feature for the high Ki-67 PI GISTs group, with an odds ratio (OR) value of 30.037 (95% CI: 5.707-158.106). CONCLUSIONS: Imaging features, including the presence of necrosis, high necrosis degree, thick wall of necrosis, and HYOM were significant predictive indicators for the high Ki-67 PI GISTs group.