Mutations in CERS3 Gene Underlies a Case of Autosomal Recessive Congenital Ichthyosis / 罕见病研究

Autosomal recessive congenital ichthyosis caused by CERS3 mutations is extremely rare in clinical practice. We recently identified a family of autosomal recessive congenital ichthyosis and performed multigene exome sequencing for hereditary skin diseases to identify causative genes. Mutation analysis revealed compound heterozygous mutations of c.746A>G(from the mother) and exon12 deletion(from the father)in CERS3 were detected in the proband, which were verified by Sanger sequencing and co-segregated with the ichthyosis phenotype in the proband and her parents. These mutations were both reported for the first time. For the treatment, the proband received an oral acitretin capsules of 20 mg once daily. After 3-month follow up, the patient's lesion improved significantly.

Analysis of the genome and transmission characteristics of an aggregated novel coronavirus infection based on metagenomic next-generation sequencing / 中华地方病学杂志

Objective:To analyze the viral genome sequence of novel coronavirus infected persons in Baotou City, understand the mutation characteristics of novel coronavirus genome in the process of transmission among cases, and explore the transmission rule of novel coronavirus in the clustered populations.Methods:Nine throat swabs samples (No. 1 - 7, No. 9, and No. 10), two sputum samples (No. 8, No. 11, and No. 11 sample was from No. 10 case), and one surface smear sample (No.12, and No. 12 sample was from No. 10 case) were collected from 10 confirmed cases of novel coronavirus infection in Baotou City from January 25 to February 21, 2020. Samples 1 and 3 were from single cases, and the rest were from clustered cases. The virus genome was sequenced by metagenomic next-generation sequencing (mNGS), and single nucleotide polymorphism (SNP) mutation sites were screened by comparing with NC_045512, a reference strain of novel coronavirus. Combined with relevant epidemiological information, gene mutation, virus typing, and evolutionary traceability analysis were carried out.Results:The results of viral genome mNGS showed that 76 SNP mutation sites were detected in 12 samples compared with the reference strain NC_045512, including 3 (3.95%) transitions and 73 (96.05%) reversals. There were 19 (25.00%) synonymous mutations and 57 (75.00%) non-synonymous mutations. The analysis of nucleotide and amino acid variation sites showed that mutations were found at five sites (T2821C, C6548T, T16464C, G16858A and T251C) in all the clustered cases (cases 2, 4 - 10). In the single cases, sample 1 had mutations at C9245T and A15340T, and sample 3 had mutation at C13T. The virus typing analysis showed that the samples 1 and 3 belonged to the L type of novel coronavirus, while the rest belonged to the S type of novel coronavirus. The results of genomic evolutionary relationship analysis showed that all the samples could be divided into two branches. The branches of sample 1 and 3 belonged to single cases, and the rest belonged to family clustered cases.Conclusion:The genomic characteristics of the clustered cases of novel coronavirus infection in Baotou City are basically consistent with the epidemiological investigation results, and the transmission of the virus is mainly related to close contact and family gathering.

Cutaneous manifestations of COVID-19 / 中华皮肤科杂志

COVID-19 can be accompanied by a variety of cutaneous abnormalities, which mainly include vascular lesions (chilblain-like lesions, livedo reticularis, purpura, ecchymosis, acral cyanosis, gangrene, etc) and inflammatory lesions (diffuse erythema, morbilliform exanthem, acute urticaria, varicella-like exanthem, etc) . Some types of skin lesions may be the first symptom or the only clinical manifestation of COVID-19.

The role of histone deacetylases 1/2 in regulating murine oogenesis / 生理学报

Oogenesis is the basic reproductive process of female mammals and is essential for fertilization and embryo development. Recent studies have shown that epigenetic modifications play an important role in the regulation of mammalian reproductive processes (such as oogenesis, spermatogenesis, preimplantation embryo development and sex differentiation). Taking histone acetylation as an instance, the dynamic changes of histone acetyltransferases (HATs) and deacetylases (HDACs) are involved in the regulation of gene activation and inactivation when numerous key physiological events occur during reproduction. Thereinto, HDAC1 and HDAC2, which are highly homologous in terms of both structure and function, play a pivotal role in murine oogenesis. HDAC1 and 2 jointly regulate the global transcription and the incidence of apoptosis of growing oocytes and affect its subsequent growth and development, which reflects their compensatory function. In addition, HDAC1 and 2 also play a specific part in oogenesis respectively. It has shown that HDAC2 is more critical than HDAC1 for oocyte development, which regulates de novo DNA methylation and chromosome segregation. Reciprocally, HDAC1 is more critical than HDAC2 for preimplantation development. Deficiency of HDAC1 causes the decreased proliferation of embryonic stem cells and the smaller embryoid bodies with irregular shape. In this review, we summarized the role and the current research progress of HDAC1/2 in murine oogenesis, to provide a reference for further understanding the relationship between epigenetic modifications and reproductive regulation.

Combined Effect of Smoking and Obesity on Coronary Heart Disease Mortality in Male Veterans: A 30-year Cohort Study / 生物医学与环境科学（英文）

Objective@#Evidence is lacking regarding the combined effects of smoking and obesity on mortality from coronary heart disease in male veterans. This study aimed to explore the combined effect of smoking and obesity on coronary heart disease mortality in male veterans in China.@*Methods@#A cohort of 1,268 male veterans from 22 veteran centers in Xi'an (Shaanxi Province, China) were followed up once every 2 years from February 1, 1987 to October 30, 2016. The endpoint was death from any cause. The hazard ratio ( @*Results@#The total follow-up was 24394.21 person-years; each subject was followed up for a mean duration of 19.24 years. By the end of the study, of the 1,268 veterans, 889 had died, 363 were alive, and 16 were lost to follow-up. Cox regression analysis results revealed that current smoking ( @*Conclusion@#Our results suggest that obese veterans who smoke might be an important target population for coronary heart disease mortality control.

3D disorganization and rearrangement of genome provide insights into pathogenesis of NAFLD by integrated Hi-C, Nanopore, and RNA sequencing

The three-dimensional (3D) conformation of chromatin is integral to the precise regulation of gene expression. The 3D genome and genomic variations in non-alcoholic fatty liver disease (NAFLD) are largely unknown, despite their key roles in cellular function and physiological processes. High-throughput chromosome conformation capture (Hi-C), Nanopore sequencing, and RNA-sequencing (RNA-seq) assays were performed on the liver of normal and NAFLD mice. A high-resolution 3D chromatin interaction map was generated to examine different 3D genome hierarchies including A/B compartments, topologically associated domains (TADs), and chromatin loops by Hi-C, and whole genome sequencing identifying structural variations (SVs) and copy number variations (CNVs) by Nanopore sequencing. We identified variations in thousands of regions across the genome with respect to 3D chromatin organization and genomic rearrangements, between normal and NAFLD mice, and revealed gene dysregulation frequently accompanied by these variations. Candidate target genes were identified in NAFLD, impacted by genetic rearrangements and spatial organization disruption. Our data provide a high-resolution 3D genome interaction resource for NAFLD investigations, revealed the relationship among genetic rearrangements, spatial organization disruption, and gene regulation, and identified candidate genes associated with these variations implicated in the pathogenesis of NAFLD. The newly findings offer insights into novel mechanisms of NAFLD pathogenesis and can provide a new conceptual framework for NAFLD therapy.

Mechanism of Huangjingwan in Inhibiting Tau Hyperphosphorylation in Hippocampal Neurons of Mice with Alzheimer's Disease Induced by D-galactose and Okadaic Acid Resulting in Learning and Memory Disorders / 中国实验方剂学杂志

Objective:To investigate the effect of Huangjingwan （HW） on the activities of glycogen synthase kinase-3β （GSK-3β）， protein phosphatase 2A （PP2A） and the mechanism in inhibiting tau protein hyperphosphorylation in the hippocampal neurons of mice with Alzheimer's disease. Method:After subcutaneous injection with 1.0% D-galactose （0.14 g·kg-1·d-1） into the back and neck of mice for 4 weeks， the right ventricle of mice was injected with 2 μL （75 ng） of okadaic acid for one time to make AD model， and the successfully modeled AD mice were selected by Morris water maze. Then， the selected AD mice were randomly divided into AD model group， memantine group （1.3×10-3 g·kg-1·d-1） and HW group （2.5 g·kg-1·d-1）. In addition， the sham model control group and the normal control group were set up. At the same time， 2 μL normal saline was injected into the right ventricle of mouse in the sham model control group for modeling control. Two weeks after modeling， the mice in the two experimental drug groups were given the corresponding dose of the experimental drug by gavage for 4 weeks. In addition， after 2 weeks of AD modeling， mice in control group and AD model group were intragastrically administrated with the same amount of normal saline daily for 4 weeks. The mice in normal control group were only given daily feed. At the end of gavage， all the mice were tested by the open field experiment and jumping platform experiment to evaluate the differences in exploratory activity ability， anxiety level and learning and memory ability. The number of neurons in CA1 and CA3 areas of hippocampus in all the mice was detected by Nissl staining. Quantitative real-time polymerase chain reaction （Real-time PCR） was used to detect mRNA expressions of GSK-3β and PP2A in hippocampus of mice in each group. Protein expressions of GSK-3β， PP2A， phosphorylated tau （p-tau） and total tau protein （t-tau） in hippocampus of mice in each group were detected by Western blot. Result:Compared with the normal control group， mice in AD model group showed an obvious dementia state， which was characterized by a lower spontaneous activity， lower exploration behavior ability， higher anxiety level， less movement and easier to stay and hide， longer learning response time， significantly increased number of learning and memory errors， and decreased numbers of hippocampal neuron in CA1 and CA3 areas， and reduced mRNA and protein expressions of PP2A， mRNA and protein expressions of GSK-3β， p-tau protein and the ratio of p-tau/t-tau were all increased significantly （P<0.01）， while expression of t-tau protein was decreased， with no significant difference. Compared with the AD model group， mice in the HW group showed a higher spontaneous activity， higher exploration ability， lower anxiety level， higher learning and memory performance， and the numbers of hippocampal neuron in CA1 and CA3 areas increased， while mRNA and protein expressions of PP2A increased， and the mRNA and protein expressions of GSK-3β， the expression of p-tau protein and the ratio of p-tau/t-tau were all decreased significantly （P<0.01）， but with no significant difference in the protein expression of t-tau. Conclusion:HW can inhibit tau hyperphosphorylation in hippocampal neurons of AD mice， restore tau protein function， protect hippocampal neurons， and exert an anti-AD effect， which may be related to the regulatory mechanism in the activity balance between GSK-3β and PP2A in hippocampal neurons.

Effect of Huangjingwan on Expressions of Wnt/β-catenin Signal Pathway-associated Proteins in Hippocampus of Mice with Alzheimer's Disease Induced by D-galactose and Okadaic Acid with Learning and Memory Disorders / 中国实验方剂学杂志

Objective:To explore the effect of Huangjingwan （HW） on the expressions of Wnt/β-catenin signal pathway-associated proteins in the hippocampus of mice with Alzheimer's disease （AD） induced by D-galactose and okadaic acid with learning and memory disorders， as well as its mechanism. Method:After subcutaneous injection with 1.0% D-galactose （0.14 g·kg-1·d-1） into the back and neck of mice for 4 weeks， the right ventricle of mice was injected with 2 μL（75 ng） of okadaic acid for one time to make AD model， and the successfully modeled AD mice were selected by Morris water maze. Then， the selected AD mice were randomly divided into AD model group， memantine group （1.3×10-3 g·kg-1·d-1） and HW group （2.5 g·kg-1·d-1）. In addition， the sham model control group and the normal control group were set up. At the same time， 2 μL normal saline was injected into the right ventricle of mouse in the sham model control group as the modeling control. Two weeks after molding， the mice in the two experimental drug groups were given the corresponding dose of the experimental drug by gavage for 4 weeks. In addition， after 2 weeks of AD modeling， mice in sham model control group and AD model group were intragastrically administrated with the same amount of normal saline daily for 4 weeks. There was no special treatment in the normal control group. At the end of gavage， the shuttle experiment was performed to detect the differences in learning and memory levels of mice in each group. The changes of β-catenin and GSK-3β positive neurons in CA1 area of hippocampus in each group were tested by immunohistochemistry. Quantitative real-time polymerase chain reaction （Real-time PCR） was used to measure the mRNA expressions of GSK-3β， β-catenin and CyclinD1 in hippocampus of mice in each group. The Western blot was used to detect the expressions of total GSK-3β （t-GSK-3β）， phosphorylation of GSK-3β at Ser9 （p-Ser9-GSK-3β）， phosphorylation of GSK-3β at Tyr216 （p-Tyr216-GSK-3β）， total β-catenin （t-β-catenin）， phosphorylation of β-catenin （p-β-catenin） and CyclinD1 proteins in hippocampus of mice in each group. Result:Compared with the normal control group， mice in AD model group showed an obvious dementia state， which was characterized by significant declines in learning and memory ability， the number of β-catenin immunoreactive neurons in hippocampal CA1 area， the mRNA and protein expressions of t-β-catenin and CyclinD1， the protein expressions of p-Ser9-GSK-3β， and the ratio of p-Ser9-GSK-3β/t-GSK-3β and p-Tyr216-GSK-3β/t-GSK-3β in hippocampal region （P<0.01）， and significant increases in the number of GSK-3β immunoreactive neurons in hippocampal CA1 area， the mRNA and protein expressions of t-GSK-3β， the protein expressions of p-Tyr216-GSK-3β and p-β-catenin， the ratio of p-β-catenin/t-β-catenin in hippocampal region （P<0.01 respectively）. Compared with the AD model group， the dementia symptoms of mice in HW group were significantly alleviated， and the number of β-catenin immunoreactive neurons in hippocampal CA1 area， the mRNA and protein expressions of t-β-catenin and CyclinD1， the protein level of p-Ser9-GSK-3β， the ratio of p-Ser9-GSK-3β/t-GSK-3β in hippocampal region were all significantly increased （P<0.01 respectively）， whereas the number of GSK-3β immunoreactive neurons in hippocampal CA1 area， the mRNA and protein expressions of t-GSK-3β， the proteins expressions of p-Tyr216-GSK-3β and p-β-catenin， the ratio of p-β-catenin/t-β-catenin in hippocampal region were all significantly decreased （P<0.01 respectively）， but the ratio of p-Tyr216-GSK-3β/t-GSK-3β has no significant statistical difference. Conclusion:HW shows the role of AD treatment， which can down-regulate the expression of GSK-3β in the hippocampus of AD mice and reduce its protein activity， and up-regulate the expression of β-catenin as well as increase its protein activity， so as to enhance the expression of downstream CyclinD1 and promote the transcription of the target genes. Its mechanism may be related to the activation of Wnt/β-catenin signal pathway.

Effect of β-catenin RNAi Interference on Signal Mechanism of Huangjingwan in Treating Learning and Memory Impairment Mice / 中国实验方剂学杂志

Objective:To treat mice with Alzheimer's disease （AD） with β-catenin RNA interference （RNAi） Huangjingwan （HW）， so as to explore the neuroprotective signal mechanism of its prevention and treatment of AD. Method:A total of 81 male Kunming mice were randomly divided into normal control group， sham model control group， AD model group， Donepezil group， HW+scrambled group， HW+RNAi group， HW group， with 8 mice in each of donepezil group and HW group， and 13 mice in each of other groups. The AD models were established through injection with D-galactose and scopolamine in the last 5 groups for 5 consecutive weeks. On the 1st day of the 4th week after modeling， 0.75 μL PEI-LMW/β-catenin siRNAs nano-complex was injected into the right lateral ventricle of each mouse in for one time to treat with β-catenin RNAi in mice brains of the HW+RNAi group. The 0.75 μL complex was injected into the right lateral ventricle of each mouse for one time as for β-catenin interference control of the HW+scrambled group. The 0.75 μL normal saline was injected into the right lateral ventricle of each mouse in one time of the sham control group. Two weeks after intracerebroventricular injection， β-catenin RNAi was confirmed to be successful， and Donepezil （6.5×10-4 g·kg-1） was intragastrically administered to each mouse of donepezil group. HW （2.5 g·kg-1） was intragastrically administered to each mouse of HW group， HW+RNAi group and HW+scrambled group. Normal saline （0.5 mL·d-1） was intragastrically administered to each mouse of the sham control group. All gastric perfusion lasted for 4 weeks. At the end of gavage， the difference in learning and memory ability of mice was evaluated by platform jumping test. Nissl staining was used to count the number of neurons in s1Tr area of cerebral cortex and CA1 and CA3 areas of hippocampus of each mouse in each group. The mRNA expressions of Wnt1， DVL2， GSK-3β， β-catenin and CyclinD1 in mice brain of each group were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Western blot was used to detect the expressions of Wnt1， DVL2， GSK-3β， β-catenin and CyclinD1 in mice brain of each group. Result:The expression of β-catenin could be significantly inhibited through the injection with PEI-LMW/β-catenin siRNAs nano-complex into the lateral ventricle of AD mice， and nearly no β-catenin expression could be detected， which successfully achieved gene silencing. Compared with the normal control group， mice in AD model group showed that the learning and memory performance decreased significantly， the number of jumping errors increased （P<0.01）， the number of neurons in S1Tr area of cerebral cortex and CA1， CA3 areas of hippocampus decreased significantly （P<0.01）， the mRNA and protein expressions of Wnt1， DVL2， β-catenin， CyclinD1 in brain decreased significantly （P<0.01）， while the mRNA and protein expressions of GSK-3β increased significantly （P<0.01）. Compared with the AD model group， mice in HW group showed that the learning and memory performance increased significantly， the number of jumping errors decreased， the number of neurons in S1Tr area of cerebral cortex and CA1， CA3 areas of hippocampus increased significantly， the mRNA and protein expressions of Wnt1， DVL2， β-catenin， CyclinD1 in brain increased significantly， while the mRNA and protein expression of GSK-3β decreased significantly （P<0.01）. Compared with the HW group， mice in HW+RNAi group showed that the learning and memory performance decreased significantly， the number of jumping errors increased significantly （P<0.01）， the number of neurons in S1Tr area of cerebral cortex and CA1， CA3 areas of hippocampus decreased significantly （P<0.01）， there was no significant change in mRNA and protein expressions of Wnt1， DVL2， GSK-3β in the brain， and the mRNA and protein expressions of β-catenin， CyclinD1 decreased significantly （P<0.01）. Conclusion:HW can treat and prevent AD by activating Wnt/β-catenin signal pathway.

Clinical analysis of 380 botulism patients caused by cosmetic injection of botulinum toxin / 中华急诊医学杂志

Objective:To analyze and summarize the basic characteristics and clinical features of botulism patients caused by cosmetic injection of botulinum toxin.Methods:Retrospective investigation and analysis method were used to analyze the data of botulism patients caused by cosmetic injection of botulinum toxin admitted to the Poisoning Treatment Center of the PLA from March 2016 to June 2019.Results:Total of 380 cases were included in this study, including 114 hospitalized cases and 266 emergency cases. The majority patients (97.4%) were female, and most of them (39.5%) were among 30-39 years old. Most of the cases occurred in beauty salons or beauty studios, and most of the botulinum toxin injected was fake and inferior products. Onset latency were mainly distributed in 3 to 6 days. Common clinical symptoms included dizziness, blurred vision, eyes open weakness, dysphagia, chest tightness of breath, fatigue, diplopia, nausea, bilateral eyelid drooping, and dysarthria. The "4D" sign of cranial nerve injury occurred less frequently, mainly with mild and moderate poisoning; The occurrence rates of dysarthria, dysphagia, eyes open weakness, blurred vision, choking in drinking water, chewing weakness, bilateral eyelid drooping, decreased limb muscle strength, and chest tightness of breath in the hospitalized case were significantly higher than those in the emergency cases (all P < 0.05). Three hundred and nine patients received botulinum antitoxin therapy. The dose of botulinum antitoxin was 20 000 (20 000-30 000) U, with a total treatment duration of 4 (3-7) days in the emergence cases, and 30 000 (30 000-50 000) U with a total treatment time of 8 (5-11) days in the hospitalized cases, and there were significant differences between the two groups ( P < 0.05). All cases were followed up with good prognosis. Conclusions:Cosmetic injection of botulinum toxin has certain risk. If symptoms of poisoning occur such as dizziness, blurred vision, eyes open weakness and dysphagia, patients should be treated promptly, and early treatment with botulinum antitoxin can improve the prognosis.

Development of a cell-based diagnostic system for vitamin K-dependent coagulation factor deficiency 1 / 中华医学遗传学杂志

OBJECTIVE@#To develop a cell-based system for the diagnosis of vitamin K-dependent coagulation factor deficiency 1 (VKCFD1).@*METHODS@#In HEK293 cells stably expressing the reporter gene FIX-Gla-PC, the gamma-glutamyl carboxylase (GGCX) gene was knocked out by using CRISPR/Cas9 technology. Enzyme-linked immunosorbent assay (ELISA), DNA sequencing and Western blotting were used to identify the GGCX gene knockout cells. A quickchange point variant method was used to construct the GGCX variant. ELISA was used to assess the influence of GGCX variant on the activity of reporter gene.@*RESULTS@#Two monoclonal cell lines with no reporter activity by ELISA was identified. Edition and knockout of the GGCX gene was confirmed by DNA sequencing and Western blotting. The activity of the reporter gene was recovered by transfection of the wild-type GGCX gene. Thereby two monoclonal cells with GGCX knockout were obtained. By comparing the wild-type and pathogenic GGCX variants, the reporter activity was decreased in the pathogenic variants significantly.@*CONCLUSION@#A cell-based system for the detection of GGCX activity was successfully developed, which can be used for the diagnosis of VKCFD1 caused by GGCX variants.

Effect of Huangjingwan on Antioxidant Functions and Aβ1-42 and APP Protein Expressions in Brain of Alzheimer' s Disease Rats / 中国实验方剂学杂志

Objective::To observe the effect of Huangjingwan (HW) on antioxidant functions and β-amyloid 1-42 (Aβ1-42) and amyloid precursor protein (APP) expressions in the brain of Alzheimer' s disease (AD) rats. Method::SD rats were randomly divided into normal control group, sham model control group, AD model group, and low, medium, high-dose (equivalent raw drug dose 1, 3, 9 g·kg-1·d-1) HW groups.The AD models were established through intraperitoneal injection with 1.25% D-galactose (120 mg·kg-1·d-1, 6 consecutive weeks) and then one-time right ventricular injection with Aβ1-42 (10 μg). Two weeks after modeling, the rats in each HW group received corresponding drugs through intragastric administration, once a day, while the rats in sham model control group, AD model group were given normal saline 1 mL through intragastric administration, once a day.Gastric perfusion lasted for 8 weeks.At the end of the experiment, learning and memory abilities of the rats were assessed by Platform Jumping Test.The changes of physical endurance in rats were tested by 10% weight swimming under load.The activities of superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GSH-Px) antioxidant enzymes and the contents of glutathione (GSH) and malondialdehyde (MDA) in rat brain tissue were detected by colorimetry.The changes of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), Aβ1-42 and APP protein in rat brain tissues were determined by enzyme linked immunosorbent assay (ELISA). Western blot analysis was used to measure the expression of APP protein in rat brain. Result::Compared with the normal control group, rats in AD model group showed an obvious dementia state, that is more lying and less movement, longer learning response time, significant increase in the number of learning and memory errors, significant attenuation in physical fitness, significant decrease in the activities of antioxidant enzymes (SOD, GR, GSH-Px) and anti-inflammatory factors GSH in brain, significant rise in the levels of inflammatory factors MDA, IL-1β and TNF-α and the content of Aβ1-42 protein, and significant reduction in the content of APP protein in brain (P<0.01). Low, medium and high-dose HW could ameliorate dementia symptoms in AD rats, improve the achievement of learning and memory, antagonize body weakness and increase physical fitness, promote SOD, GR, GSH-Px activities and anti-inflammatory factor GSH level in the brain, reduce the levels of MDA, IL-1β and TNF-α in the brain, decrease the level of Aβ1-42 and increase the level of APP protein in the brains of AD rats compared with the AD model group (P<0.05, P<0.01), besides, within the dose range of 1-9 g·kg-1·d-1, HW has a more obvious effect with the increase of dose. Conclusion::HW has the effects in preventing and treating AD, which is related to the HW' s mechanisms in enhancing the function of antioxidant system in brain, reducing neuroinflammatory reaction and deposition of Aβ1-42 induced by oxidative stress, and maintaining the expression level of APP protein.

Synthesis and evaluation of necrosis avidity of MRI contrast agent Gd-DO3A-Ether-Rhein / 中国药科大学学报

@#The aim of this study was to synthesize and evaluate the necrosis avidity of MRI contrast agent based on rhein and linked by ether. The novel ligand 10-{［6-(1, 8-dihydroxyanthraquinone-3-carboxamido)ethoxyethyl］amino}carbonylmethyl-1, 4, 7, 10-tetraazacyclododecan-1, 4, 7-triacetic acid(DO3A-Ether-Rhein, E1)was synthesized by two steps of acylation and deprotection reaction. The paramagnetic gadolinium 10-{［6-(1, 8-dihydroxyanthraquinone-3-carboxamido)ethoxyethyl］amino}carbonylmethyl-1, 4, 7, 10-tetraazacyclododecan-1, 4, 7-triacetic acid(Gd-DO3A-Ether-Rhein, GdE1)was obtained by coordination of Gd3+ with the above ligand. We examined the necrotic avidity of GdE1 in human hepatocellular carcinoma HepG2 cell necrosis induced by hyperthermia in vitro and in rat model with muscular necrosis induced by microwave ablation in vivo by MRI. The MRI was implemented before administration of GdE1 and during 0-9 h after administration of GdE1(0. 1 mmol/kg), and Gd-DOTA(gadolinium 1, 4, 7, 10-tetraacetic acid-1, 4, 7, 10-tetraazacyclo dodecane)was used as control. The signal intensity of necrotic cells(4 369±70)was significantly higher than that of normal cells(2 555±84)(P< 0. 05). Similarly, the contrast ratio between necrotic and normal muscle at 3 h after administration of GdE1(2. 00±0. 12)was remarkblely higher than that at 0 h after administration of GdE1(1. 27±0. 03)(P< 0. 05). Therefore, GdE1 presents good necrosis affinity and has the potential to be used in the diagnosis of necrosis-related diseases.

Study of coxsackievirus A6 infection in Mongolian gerbils / 中华实验和临床病毒学杂志

Objective@#To study infection of coxsackievirus A6 (CV-A6) in Mongolian gerbils.@*Methods@#To screen the optimal ages of Mongolian gerbils, five groups with different ages were infected with 1×105 TCID50 dose of CV-A6 XS45 strain by intraperitoneal, and symptom scores of Mongolian gerbils were collected. Then to estimate the dose-effect, three doses of virus were injected to the Mongolian gerbils. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry(IHC) were used to determine virus load and tissues infection in muscle, brain and intestinal tract.@*Results@#Mongolian gerbils infected with 1×105 TCID50 dose CV-A6 consistently exhibited clinical signs, and the morbidity (death) rates of five age groups were up to 100%. There was a positive correlation between the trend of symptom scores changes and ages. The morbidity (death) rates of three doses (1×103 TCID50, 1×104 TCID50, 1×105 TCID50) also were up to 100% in 28 days Mongolian gerbils. The correlation between the trend of symptom scores changes and doses were negative. Virus loads were detected in muscle, brain and intestinal tract of pathogenesis animal. The virus loads of muscle were higher than others. IHC results showed virus infection and cytopathic effects in three tissues.@*Conclusions@#Mongolian gerbils had high susceptibility to CV-A6, and were best for animal model of CV-A6 infection.

Paeoniflorin inhibits programmed cell death-1-ligand 1 expression in HepG2 cells by regulating JAK/STAT3 signal pathway / 中国药科大学学报

@#In order to explore the effect and its mechanism of paeoniflorin on PD-L1, a PD-L1 high expression cell model was established in interferon gamma(IFN-γ)-induced HepG2 cells. The cytotoxicity of paeoniflorin was detected by MTT assay. Flow cytometry, ELISA and RT-PCR were performed to detect protein and mRNA levels of PD-L1 regulated by paeoniflorin. In HepG2 cells and Jurkat T cell co-culture system, the expression of IL-2 was detected by ELISA. Besides, T cell proliferation was evaluated by CCK-8 method, and the protein expression levels of PD-L1, JAK and STAT3 after drug treatment were determined by Western blot. These results indicated that paeoniflorin could significantly down-regulate the levels of PD-L1 protein and mRNA. In addition, it increased the number of T cells and the concentration of IL-2 in the co-culture system. Furthermore, paeoniflorin could significantly inhibit the protein expression of JAK and STAT3. Au the above experimental data indicated that paeoniflorin could down-regulate the expression of PD-L1, and its mechanism might be related to the JAK/STAT3 pathway.

Association of body mass index and waist circumference with major chronic diseases in Chinese adults / 中华流行病学杂志

Objective@#To examine the association of BMI with major chronic diseases morbidity and all-cause mortality in Chinese adults.@*Methods@#This study is based on China Kadoorie Biobank. Anthropometric indexes were objectively measured at the baseline survey during 2004-2008. After excluding participants with heart disease, stroke, cancer, COPD and diabetes, 428 113 participants aged 30 to 79 years were included in the analysis. Cox regression models were used to investigate the associations of BMI and waist circumference with incidence of major chronic diseases (including cardiovascular disease, cancer, COPD, and type 2 diabetes) and all-cause mortality.@*Results@#Over an average of 10 years, 131 454 participants developed any one of major chronic diseases. A total of 26 892 all-cause deaths were reported. The risk of major chronic diseases increased with BMI. Compared with normal BMI (18.5-24.0 kg/m2), the HR (95%CI) of overweight (BMI 24.0-28.0 kg/m2) and obesity (BMI≥28.0 kg/m2) were 1.26 (95%CI: 1.24-1.27) and 1.59 (95%CI: 1.57-1.62) respectively. Underweight and obesity were both associated with risk of all-cause mortality. Waist circumference was positively associated with risk of major chronic diseases and all-cause mortality. According to recommended cut-off points of BMI and waist circumference for Chinese adults, maintaining a healthy body weight would prevent 12% incident cases of major chronic diseases.@*Conclusion@#General and central obesity were risk factors for major chronic disease among Chinese adults.

The cut-off points of body mass index and waist circumference for predicting metabolic risk factors in Chinese adults / 中华流行病学杂志

Objective@#To assess the association of BMI and waist circumference (WC) with metabolic risk factors, and confirm the appropriate cut-off points of BMI and WC among Chinese adults.@*Methods@#After excluding participants with missing or extreme measurement values, as well as individuals with self-reported histories of cancer, a total of 501 201 adults in baseline and 19 201 adults in the second re-survey from the China Kadoorie Biobank were included. The associations of BMI and WC with metabolic risk factors were estimated. Receiver operating characteristic (ROC) analyses were conducted to assess the appropriate cut-off values of BMI and WC to predict the risk of hypertension, diabetes, dyslipidemia and clustering of risk factors.@*Results@#The prevalence of hypertension, diabetes, dyslipidemia and clustering of risk factors all presented ascending trends with the increasing levels of BMI or WC. Defined as the points on the ROC curve where Youden’s index reached the highest, the appropriate overweight cut-off points of BMI were around 24.0 kg/m2 both in men and women, and the points of WC were around 85 cm in men and 80 to 85 cm in women. With specificity 90% for identification of risk factors, the appropriate obese cut-off points of BMI were around 28.0 kg/m2 both in men and women, with the range of 27.0 to 28.9 kg/m2.@*Conclusions@#The cut-off points for overweight and obesity recommended by Coorperative Meta-analysis Group of China Obesity Task Force was verified in the large sample survey conducted more recently. The cut-off points of BMI were 24.0 and 28.0 kg/m2 for overweight and obesity, and the cut-off point of WC was 85 cm in men and 80 to 85 cm in women for central obesity.

Analysis of characteristics and influencing factors of fine particulate matters and submicron particulate matters in printing shop / 中华预防医学杂志

Objective@#To analyze the physical characteristics of fine particulate matters (PM2.5) and submicron particulate matters (PM1), and investigate the factors influencing the emission peak of printer particles.@*Methods@#A 12-hour particle concentration monitoring for PM2.5 and PM1 was conducted in a printing shop on January 5th, 2018. PM2.5 in the air was analyzed after the monitoring process to figure out morphological characteristics and element composition of printer particles. Besides, experiments were carried out in an enclosed space to detect the number concentration peaks of PM1 during every printing process. Influencing factors investigated in this study were printer types, toner coverages and interval time between different printing processes.@*Results@#The 12-hour particles concentration monitoring showed that the number concentration of PM1 and the mass concentration of PM2.5 were 7.510×104 pt/cm3 and 96.85 μg/m3. The diameter of most PM2.5 was less than 100 nm, with a fractal dimension of 2.591. Most PM2.5 appeared as regular spheres with typical agglomeration phenomenon, while some were in rhabditiform or irregular shapes. Element analysis showed that PM2.5 was mainly composed of C, O, Si, Ca, with less metallic element. The PM1 emission peak values of three printers were 3.60×104, 3.43×104, 0.31×104 pt/cm3, respectively and the difference was not statistically significant (χ2=5.42, P>0.05). When the page coverage rate was 0%, 2.5%, 5%, 10%, 20% and 50%, the PM1 emission peak value of printer A was 6.74×104, 4.62×104, 3.82×104, 2.82×104, 1.00×104 and 1.08×104 pt/cm3, and the difference was also not statistically significant (χ2=7.01, P>0.05). The natural logarithm of PM1 emission peak value in printing work was associated with the resting time before printing and the change value of heating roller temperature (r value was 0.83 and 0.89, respectively, all P values<0.05).@*Conclusion@#PM2.5 and PM1 in the printing shop stayed at a high level. Particles appeared as various shapes and element compositions were complex. The temperature change of heating roller was one of most important factors that lead to the increased number concentration peak of PM1.

Artificial intelligence in medicine / 中华皮肤科杂志

With the development of medical technology,a new era of "big data" and "precision medicine" is coming.Artificial intelligence can assist in the diagnosis and treatment process,and reduce the pressure of data analysis on physicians.At present,artificial intelligence is mainly applied to image recognition,genetics and genomics,intelligent diagnosis and treatment,and prognosis prediction in medicine,whose accuracy may approach human experts.Image recognition is most studied,including skin image recognition.In non-image recognition field,artificial intelligence is less studied in dermatology.In the future,artificial intelligence will increase the efficiency of diagnosis and treatment,so as to benefit both physicians and patients.

Metamorphopsia change and influence factors before and after idiopathic epiretinal membrane surgery / 中华实验眼科杂志

Objective To investigate the changes of metamorphopsia between before and after surgery in the patients with idiopathic epiretinal membrane and its influence factors.Methods A series cases observitional study included 39 eyes of 39 patients with idiopathic epiretinal membrane.Follow-up was carried out at 1 week before surgery and 3,6 months after surgery respectively.M-chart was used to quantify the severity of metamorphopsia (M-score).EDTRS visual chart was used to quantify best corrected visual acuity (BCVA) (converted to LogMAR).Central subfield thickness (CST),central foveal volumn (CV),cube average thickness (CAT),central foveal thichness (CFT),ganglion cell layer (GCL) thickness,inner nuclear layer (INL) thickness,outer nuclear layer (ONL) and outer plexiform layer (OPL) thickness,the integrity of external limiting membrane,ellipsoid zone and interdigitation zone were analyzed by using spectral domain-optical coherence tomography (OCT).This study protocol was approved by Ethic Committee of Beijing Tongren Hospital (No.TRECKY-012).Written informed consent was obtained from each subject before surgery.Results Mean M-score was significantly decreased from 0.8 (0.3,1.1) before surgery to 0.5 (0.2,0.8) at 3 months after surgery,with a significant difference between the two time points (Z=-2.013,P=0.044).Mean M-score was 0.6(0.2,0.8) at 6 months after surgery,which was not significantly different in comparison with before surgery and 3 months after surgery (Z =-1.873,P =0.061;Z =-0.288,P =0.773).Compared with before surgery,the horizontal M-score was significantly decreased 3 months and 6 months after surgery (Z =-2.329,P =0.020;Z =-2.858,P =0.004).No significant difference was found in vertical M-score among before surgery and 3,6 months after surgery (all at P＞0.05).The BCVA was improved from 0.40 (0.30,0.66) before surgery to 0.20 (0.06,0.42) 3 months after surgery and declined to 0.30 (0.10,0.52) at 6 months after surgery,and significant differences were obtained between 3 months after surgery and before surgery or 6 months after surgery (Z =-4.087,P＜0.001;Z =-2.235,P =0.025).Compared with before surgery,the BCVA in cataract combined with vitrectomy operative group was significantly improved in 3 months and 6 months after surgery (Z=-2.613,P=0.009;Z=-2.466,P=0.014) and the BCVA in only vitrectomy group was significantly improved at 3 months after surgery but decreased 6 months after surgery,showing significant differences between 3 months after surgery and before surgery or 6 months after surgery (Z =-3.104,P =0.002;Z =-3.464,P =0.001).Preoperative M-score was positively correlated with preoperative BCVA,preoperative CST or preoperative CFT (rs =0.384,P =0.016;rs =0.585,P＜0.001;rs =0.601,P＜0.001).No correlation was found between BCVA with GCL,INL or ONL + OPL thickness.Horizontal M-score was positively correlated with CST,postoperative CV and postoperative CAT (rs=0.322,P=0.045;rs=0.340,P=0.034;rs =0.336,P=0.036),and no correlation was found between horizontal M-score and BCVA,CFT,GCL thickness,INL thickness,ONL+OPL thickness in 6 months after surgery.The vertical M-score and mean M-score were not correlated with OCT parameters in 6 months after surgery.The mean M-score was positively correlated with preoperative mean M-score,preoperative CST,preoperative CV,preoperative CAT in 6 months after surgery (rs =0.589,P＜0.001;rs =0.330,P =0.040;rs =0.404,P =0.011;rs =0.410,P =0.009).In addition,and no significant correlation between mean M-score and preoperative BCVA,CFT,GCL thickness,INL thickness,ONL+OPL thickness.Multivariate stepwise linear regression showed that preoperative M-score was a predictor of postoperative M-values (adjusted R2 =0.211,P =0.002).Conclusions Most metamorphopsia can be alleviated after idiopathic epiretinal membrane surgery.The residue metamorphopsia after surgery probably is correlated with preoperative metamorphopsia and CFT.