White matter injury exacerbated anxiety-like behavior of db/db mice after distal middle cerebral artery occlusion / 中国医师进修杂志

Objective:To explore the possible mechanism of exacerbation of anxiety-like behavior in db/db mice after distal middle cerebral artery occlusion (dMCAO).Methods:The db/db mice was used to establish a type 2 diabetes mellitus model. Meanwhile, heterozygous db/+ mice and C57 wild-type (WT) mice were chosen as double control groups. Then a permanent distal middle cerebral artery occlusion model was employed as an acute ischemic stroke model. The blood glucose levels before and post-dMCAO surgery on day1, day3, and day5 were detected. The brain tissue loss at 35 days after stroke was measured by immunofluorescent staining of MAP2. The open-field test was performed to estimate anxiety-like behavior and general motor and exploring ability of the animals. Axons and myelin were immunostained with non-phosphorylated neurofilaments (SMI32) and myelin basic protein (MBP), respectively, to evaluate differences in white matter integrity in WT, db/+ and db/db mice 35 days after stroke. The correlation between SMI32/MBP and open field test parameters (time in center and corner) was analyzed. Flow cytometry was employed to detect the amount of T cells and B cells, including regulatory T cells (Tregs) in the brain tissue.Results:Blood glucose levels in db/db mice were significantly higher than db/+ mice and WT mice in both sham and dMCAO groups ( P<0.01). There was no significant difference in brain tissue loss 35 days post-stroke among db/db mice, db/+ mice, and WT mice. In the open field test, there were significant differences in the total distance of db/db mice, db/+ and WT mice in the sham and dMCAO groups. Db/db mice shorter than db/+ mice ( P<0.05), WT mice ( P<0.01), and db/+ mice shorter than WT mice ( P<0.05). There were significant time differences in the center among db/db, db/+, and WT mice in sham and dMCAO groups. In both the sham and dMCAO groups, db/db mice spent less time in the center area of the open field than WT mice ( P<0.01). In the sham group, db/+ mice spent less time in the center area than WT mice ( P<0.05). In dMCAO group, db/db mice spent less time in the center area than db/+mice ( P<0.05), and db/+ mice spent less time in the center area than WT mice ( P<0.01). For the time in the corner, in both the sham and dMCAO groups, db/db mice and db/+ mice consumed more time than WT mice ( P<0.01 or <0.05). In the dMCAO group, db/db mice spent more time in the corner than db/+ mice ( P<0.05). Referring to white matter injury, an increased SMI32/MBP ratio in EC area and CTX area (data was not shown in this article) after dMCAO in db/db, db/+ and WT mice were detected. In EC area, db/db mice have a higher SMI32 ratio than db/+ mice and WT mice: 4.24 ± 0.37 vs. 1.96 ± 0.37, 1.80 ± 0.36, both have significant differences ( P<0.01). For db/db mice and WT mice, the SMI32/MBP ratio negatively correlates with time in center and positive correlation with time in the corner. Three days after dMCAO, the total cells of CD 3+ T cells, CD 8+ cells, Tregs, in db/db mice group have significantly decreased compared to WT group: 4 079 ± 1 345 vs. 70 055 ± 3 374, 141.30 ± 28.36 vs. 2 714.00 ± 463.20, 148.00 ± 61.15 vs. 3 007.00 ± 639.90 ( P<0.01), while B cell has no change between two groups. Conclusions:By comparing the severity of anxiety-like behavior of db/db mice, the severity of white matter injury, and the number of T cells and B cells in brain tissue after dMCAO, immune-mediated brain white matter injury may aggravate db/db mice′s post-dMCAO anxiety-like behavior. Due to the gene dose effect, db/+ mice are not suitable as a control group for db/db mice in animal experiments involving anxiety-like behavior assessment.

Analysis of influencing factors in migraine combined with patent foramen ovale / 中国医师进修杂志

Objective:To investigate the influencing factors of headache degree in migraine patients with patent foramen ovale (PFO).Methods:The clinical data of 124 migraine patients with PFO from January 2013 to June 2019 in Dalian Central Hospital Affiliated to Dalian Medical University were retrospectively analyzed. The right-to-left shunt of PFO was assessed by contrast-enhanced transcranial Doppler (c-TCD); the diameter of PFO, length of PFO tunnel and the presence of atrial septal aneurysm (ASA) were detected by transesophageal echocardiography (TEE); the degree of migraine was assessed by headache impact test-6 (HIT-6) scale. The relations between right-to-left shunt volume of PFO, diameter of PFO and degree of migraine were analyzed by Goodman-Kruskal γ test; the relations between the length of PFO tunnel, ASA and degree of migraine were analyzed by Spearman rank correlation analysis.Results:Among the 124 migraine patients with PFO, the c-TCD test result showed that small shunt volume was in 20 cases, medium shunt volume in 31 cases, and large shunt volume in 73 cases. The TEE test result showed that small foramen ovale in 76 cases, medium foramen ovale in 47 cases, and large foramen ovale in 1 case; long tunnel in 57 cases, and short tunnel in 67 cases; without ASA in 91 cases, and with ASA in 33 cases. The HIT-6 score result showed that some influence in 9 cases, significantly influence in 22 cases, and serious influence in 93 cases. The Goodman-Kruskal γ test result showed that right-to-left shunt volume of PFO and diameter of PFO were positive correlation with degree of migraine ( γ = 0.66, P<0.01; γ = 0.38, P<0.05). The Spearman rank correlation analysis result showed that ASA was positive correlation with degree of migraine ( r = 0.18, P<0.05), while the length of PFO tunnel was negative correlation with degree of migraine ( r = -0.23, P<0.05). Conclusions:The right to left shunt amount of PFO, diameter of PFO and the presence of ASA are positive correlation with degree of migraine, while the length of PFO tunnel is negative correlation with degree of migraine.

The influence of the prevalence of covid-19 on intravenous thrombolytic therapy in patients with acute ischemic stroke in Dalian / 中国医师进修杂志

Objective:To investigate the influence of Covid-19 epidemic on the number of acute ischemic stroke patients with intravenous thrombolytic therapy in Dalian in 2020, the way to hospital, onset to door time (ODT), door to needle time(DNT), onset to needle time(ONT), and the National Institute of Health Stroke Scale (NIHSS) before and after intravenous thrombolytic therapy.Methods:This was a retrospective descriptive study on 13 map-participating hospitals in Dalian from August 2020 to December 2020. The number of acute ischemic stroke patients with intravenous thrombolytic therapy, ODT, DNT, ONT, modes of transport to hospital, the NIHSS score before and after intravenous thrombolytic therapy, etc were analyzed. Data were collected from August 1, 2020 to December 31, 2020, and compared with the baseline data from the same period in 2019.Results:SPSS 22.0 statistical software and Data Analysis ToolPak were used for statistical analysis of the obtained data, and T tests statistic was used for data analysis. In 2020,the number of acute ischemic stroke patients with intravenous thrombolytic therapy increased (681 cases vs 416 cases), and DNT increased [50 minutes vs 45 minutes P = 0.01]. In 2020, 83.55% of patients indicated self-visit as their main mode of transport to the hospital. In 2020, among the self-visit patients with NIHSS score<15 scores,the number of the patients with the NHISS score unchanged or decreased after intravenous thrombolytic therapy was more (562 scores vs. 535 scores, P<0.001), and the patients with NIHSS score ≥15 scores were more willing to call ambulances to hospital. Conclusions:During the Covid-19 epidemic period of 2020, the number of acute ischemic stroke patients receiving intravenous thrombolytic therapy increased, DNT increase; the patients withNIHSS score<15 scores are more willing to choose to visit the hospital using their own transportation and benefit from intravenous thrombolytic therapy. The patients with NIHSS ≥15 scores prefer to call ambulances to hospital.

Genetic analysis of three patients with Kleefstra syndrome / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical and genetic features of three patient diagnosed with Kleefstra syndrome.@*METHODS@#Whole exome sequencing (WES) was carried out for the probands and their parents. Suspected variants were validated by Sanger sequencing. Copy number variations (CNV) were detected by CNV-seq and validated by real-time PCR.@*RESULTS@#Proband 1 was found to carry a de novo heterogeneous variant (c.823+1G>T) of the EHMT1 gene, which may affect its expression. Based on the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic (PVS1+PS2+PM2). Proband 2 was found to carry a de novo missense variant c.439C>G (p.L147V) of the EHMT1 gene, which was predicted to be likely pathogenic (PS2+PM1+PM2+PP3). Proband 3 was found to carry a heterozygous 520 kb deletion at 9q34.3 by CNV-seq. The deletion has encompassed the whole of the EHMT1 gene. Real-time PCR has detected no CNV of this region in her parents.@*CONCLUSION@#Variants of the EHMT1 gene probably underlay the disease in these patients. Genetic testing has provided a basis for their clinical diagnosis.

Clinical and genetic analysis of four patients with congenital neutropenia / 中华医学遗传学杂志

OBJECTIVE@#To delineate the clinical feature and genetic basis of four patients with congenital neutropenia.@*METHODS@#All patients were subjected to whole exome sequencing (WES). Suspected variants were verified by Sanger sequencing.@*RESULTS@#The patients (two boys and two girls), aged 7 to 15 months, suffered from neutropenia and recurrent infections. Bone marrow smears showed a significant decrease in the proportion of rod-shaped and lobulated granulocytes, which suggested impaired development and maturation of bone marrow neutrophils. WES has discovered heterozygous variants (c.496G>A, c.58C>G, c.391G>A and IVS1+5T>A) of the ELANE gene in the patients. Among these, c.58C>G and IVS1+5T>A were unreported previously. Follow up revealed patients 1 and 3 had periodic neutropenia, while patients 2 and 4 had severe congenital neutropenia. After attaining the definite diagnosis, the patients were treated symptomatically.@*CONCLUSION@#The main clinical feature of congenital neutropenia is refractory recurrent bacterial infections, for which mutations of the ELANE gene are a common cause. Two novel pathogenic ELANE variants have been discovered in this study.

Preparation of Chitosan-stearic Acid Nano-micelles Modified with Folic Acid and mPEG / 中国药房

OBJECTIVE： To prepare insoluble anti-tumor drug-loading polymer micelles， and to increase inhibitive effect of insoluble anti-tumor drug. METHODS： Chitosan （CSO） and stearic acid （SA） were used to prepare blank micelles （CSO-SA）， then modified with mPEG and folic acid （FA） to prepare PEG-CSO-SA and FA-PEG-CSO-SA. Characteristic functional groups of CSO-SA， PEG-CSO-SA and FA-PEG-CSO-SA were detected by infrared spectroscopy. The morphology of micelles was observed by transmission electron microscopy. The particle size and Zeta potential of micelles were measured by laser particle size analyzer. Osthole （OST） was used as the model drug and drug-loading micelles （FA-PEG-CSO-SA/OST） were prepared by dialysis. MTT assay was used to detect the inhibitory rate of FA-PEG-CSO-SA， OST solution and FA-PEG-CSO-SA/OST to human liver cancer cell HepG2. Half inhibitory concentration （IC50） was calculated. RESULTS： FA-PEG-CSO-SA was successfully prepared. CSO-SA， PEG-CSO-SA， FA-PEG-CSO-SA were oval in shape； particle sizes were （96.01±5.99）， （112.93±1.06）， （216.01±4.76） nm （n＝3） and Zeta potentials were （39.30±1.75）， （38.03±2.91）， （15.17±2.10） mV （n＝3）， respectively. Encapsulation efficiency and drug-loading amount of OST in FA-PEG-CSO-SA were （84.47±2.07）％ and （16.01±0.90）％ （n＝3）， respectively. The inhibition rates of FA-PEG-CSO-SA to HepG2 cells were＜20％. IC50 of OST solution and FA-PEG-CSO-SA/OST to HepG2 cells were （62.08±5.21）， （27.49±0.50） μg/mL （n＝3）， respectively. CONCLUSIONS： Prepared FA-PEG-CSO-SA can significantly increase inhibitive effect of insoluble drug OST to HepG2 cells， and it is expected to become a new anti-tumor drug carrier.

Analysis of prognosis-relating factors in the elderly patients after the initial onset of delirium / 中华老年医学杂志

Objective To investigate the correlations of risk factors of age,delirium-inducing factors,dementia,delirium severity,and disease severity with the prognosis of elderly patients with delirium.Methods A total of 112 patients aged 70 years and older with initial onset of delirium during hospital stay were enrolled in this study.They were hospitalized in Dalian Municipal Central Hospital from Jan.2013 to Dec.2015.The severity of delirium was evaluated by delirium rating scalerevised-98(DRS-R-98).The acute physiology and chronic health enquiry(APACHE-Ⅱ)score and the sequential organ failure assessment(SOFA)score were recorded within 48 h after delirium onset.After periods of hospitalization of Jan.2013 to Dec.2015,patients were followed up until 31 Dec 2017.Correlations of age,delirium-inducing factors and dementia with survival time and long-term viability after delirium onset were statistically analyzed.Results Age,delirium-inducing factors,cognitive impairment,duration of cognitive impairment,type of dementia,and delirium severity had no correlations with the lifetime and long-term viability in patients with delirium.While,APACHE Ⅱ score for assessment of severity degree of delirium(P ＜0.001,r =-0.390) and SOFA score(P ＜0.001,r=-0.638)were negatively correlated with the lifetime in patients with delirium.SOFA score (P =0.004) and delirium recurrence (P ＜ 0.001) were significantly correlated with the long-term viability in patients with delirium.Conclusions The severity and recurrence of delirium are strongly correlated with the lifetime and quality of life in patients with delirium.Compared with APACHE Ⅱ score,SOFA score may have a more important clinical application value in predicting the prognosis of patients with delirium.

Effect of ligustrazine on cerebral injury in LPS-induced septic shock rats / 中国病理生理杂志

AIM: To investigate the effect of ligustrazine (Lig) on cerebral injury in LPS-induced septic shock rats and to explore the underlying mechanism.METHODS: Wistar rats (n =48) were randomly divided into control group, LPS group and LPS +Lig treatment group.The rats in LPS group were randomly divided into 2 subgroups at time points of 6 h and 12 h.After ligustrazine treatment, the venous blood was collected by removal of eyeballs to detect the con-centration of neuron-specific enolase (NSE) using ELISA.The nitric oxide (NO) concentration in the homogenate of brain tissues was examined.The apoptosis in the hippocampus was analyzed by TUNEL staining.The protein expression of Bax and Bcl-2 was determined by Western blot.RESULTS: Ligustrazine inhibited the elevation of NSE and NO concentrations in LPS-induced septic shock rats.Furthermore, ligustrazine administration also attenuated LPS-induced increase in Bax ex-pression and decrease in Bcl-2 expression.CONCLUSION: Ligustrazine decreases the concentration of NSE and NO, and attenuates cerebral injury in LPS-induced septic shock rats.These effects may be related to the regulation of Bax and Bcl-2 expression.

Effects of Rosuvastatin on Blood Lipid and Thyroid Nodules in Elderly Patients with Dyslipidemia / 中国药房

OBJECTIVE:To investigate the effects and safety of rosuvastatin on blood lipid and thyroid nodules in elderly pa-tients with dyslipidemia. METHODS:70 elderly patients with dyslipidemia were selected and randomly divided into control group (33 cases) and treatment group (37 cases). Control group was treated with routine treatment as abstain from tobacco and drink, low fat diet,Aspirin enteric-coated tablets 100 mg at bed time;treatment group was additionally treated with Rosuvastatin calcium tablet 10 mg at bed time,on the basis of control group. Both groups received the treatment for consecutive 12 weeks. BMI,blood lipid and the size of thyroid nodules were compared between 2 groups before and after treatment,and the occurrence of ADR was also observed. RESULTS:There was no significant difference in BMI between 2 groups before and after treatment (P>0.05). There was no significant difference in blood lipid level and the size of thyroid nodules between 2 groups before and after treatment (P>0.05). The blood lipid level and the size of thyroid nodule of 2 groups were improved significantly after treatment,and the treatment group was significantly better than the control group,with statistical significance(P<0.05). 2 pationts of creatment suf-fered from the increase of ALT but recovered withont angtreatment. CONCLUSIONS:Rosuvastatin can significantly improve blood lipid and decrease thyroid nodules in elderly patients with dyslipidemia with good safety.

Bilateral papillary thyroid carcinoma concurrent with parathyroid adenoma: one case report / 临床耳鼻咽喉头颈外科杂志

Concurrent thyroid carcinoma and parathyroid adenoma is rare, they can and do coexist. We present here a 63-year old man who had bilateral papillary thyroid carcinoma and a parathyroid adenoma in the right thyroid lobe. Thyroid cancer was confirmed surgically. After the operation, the patient was found hypercalcemie and hypophosphatemia along with an elevated parathyroid hormone (PTH), indicating primary hyperparathyroidism. Also, the parathyroid 99mTc-MIBI scan demonstrated parathyroid adenoma in the right lower pole of the thyroid. The abnormal parathyroid tissue was carried out, and then serum calcium and PTH levels decreased to normal ranges.

Association between polymorphism ofSLC26A9gene and clinical characteristics of asthma in children / 临床儿科杂志

ObjectiveTo investigate the association between nucleotide polymorphisms (SNP) of rs2282430 and rs2031234 inSLC26A9 gene and clinical characteristics of asthma in Han children in central China.MethodsA case-control study was performed. Two hundreds and three children with asthma were recruited in this study and 221 normal children were selected as controls. The genotypes of two SNPs inSLC26A9 gene were examined using PCR-RFLP.ResultsBetween children with asthma and controls, the distribution of three genotypes (AA, AG and GG) in rs2282430 locus had signiifcant difference (P=0.042). The percentage of AA genotype was higher in children with asthma than that in controls. In implicit mode (AAvs. AG+GG), the two groups was statistically signiifcant difference (P=0.028). The frequency of A allele was higher in children with asthma than that in controls (P=0.011). Between children with asthma and controls, the distribution of three genotypes (TT, GT, and GG) in rs12031234 locus had no signiifcant difference (P=0.479). The frequency of alleles in rs12031234 locus also had no signiifcant difference (P=0.215). Among asthmatic children with different genotype of rs2282430, the lymphocytecounts (LYM), C-reaction protein (CRP), IgE, neutrophils (NEU%), and eosinophils (EOS%) were not signiifcantly different (P>0.05). Conclu-sionsThe rs2282430 polymorphism inSLC26A9 gene is associated with childhood asthma in the central China and the A allele is the risk factor. The rs2282430 polymorphism is not associated with LYM counts, CRP level, IgE level, NEU%, and EOS%.

Screening significance of transcranial Doppler for patients with patent foramen ovale induced cerebral embolism / 中国医师进修杂志

Objective To investigate the screening significance of transcranial Doppler (TCD) for patients with patent foramen ovale ( PFO) induced cerebral embolism and to improve the treatment aiming at the causes.Methods Thirty-six patients of less than 60 years old with unknown-cause cerebral embolism and transient ischemic attack were enrolled.Besides conventional examination,the 24 h Holter,transthoracic echocariiography,carotid artery Doppler ultrasonography (CAU),routine TCD,TCD foaming test,transesophageal echocardiography (TEE),CT angiography (CTA) of head and neck,ultrasonography of vein in bilateral lower limbs were examined in all patients.Results All the patients showed no atrial fibrillation.No structural heart disease and intracardiac occupying lesion were shown in transthoracic echocardiography.No carotid stenosis was shown in carotid artery Doppler ultrasonography.Routine TCD showed no intracranial artery stenosis.No thrombus was found in ultrasonography of deep veins in bilateral lower limbs.CTA of head and neck showed everything was normal.Fourteen patients were observed with right-to-left shunt in heart by TCD foaming test,including 10 cases with microbubble signals(MBS) in 10 s,and 4 cases with MBS after Valsalva maneuver.Among 14 patients,12 patients were proved PFO by TEE.Conclusions PFO is one of the causes of cardiogenic cerebral embolism.TCD is accurate and reliable for the screening of PFO.

Expression of kringlie 1～3 of angiostatin in Pichia and activity detection / 中国生化药物杂志

Purpose　The aim is to invest the mechanism and activity of kringle1～3 gene of angiostatin. Methods　Kringle1～3 gene of angiostatin was abtained from hepatocyte of normal human by RT-PCR and inserted into expression vector pPIC9K in Pichia expression system. The recombinant protein was induced secrete , purified and test the activity by MTT.Results　　Krigle1～3 protein could inhibit vascular endothelial cell proliferative activity.Conclusion　The reaction similar apoptosis induced by kringle1～3 recombinant protein of angiostatin inhibit cell proliferation.