Clinicopathological features of hepatic fibrinogen storage disease in children / 中华病理学杂志

Objective: To investigate the clinicopathological and molecular characteristics of hepatic fibrinogen storage disease (FSD) in children. Methods: The clinical, histopathologic, immunophenotypic, ultrastructural and gene sequencing data of 4 FSD cases were collected from September 2019 to January 2021 in the Children's Hospital of Fudan University, Shanghai, China. Retrospective analysis and literature review were conducted. Results: There were 4 cases of FSD, 3 males and 1 female, aged 3 years and 3 months to 6 years (median age, 3 years and 4 months). The clinical manifestations were abnormal liver function and abnormal blood coagulation function, for which 2 cases had family genetic history. Liver biopsies revealed that, besides liver steatosis, fibrosis and inflammation, there were single or multiple eosinophilic inclusion bodies of various sizes and surrounding transparent pale halo in hepatocytes. Immunohistochemistry showed that the inclusion bodies were positive for anti-fibrinogen. Under the electron microscope, they corresponded to the dilated cisternae of the rough endoplasmic reticulum, which were occupied by compactly packed tubular structures and arranged into a fingerprint-like pattern with curved bundles. Gene sequencing revealed that the 2 cases of FGG mutation were located in exon 8 c.1106A>G (p.His369Arg) and c.905T>C (p.Leu302Pro), and 1 case was located in exon 9 c.1201C>T (p.Arg401Trp). No pathogenic variant was detected in the other case. Conclusions: FSD is a rare genetic metabolic disease and clinically manifests as abnormal liver function with hypofibrinogenemia. In the background of liver steatosis, fibrosis and inflammation, there are eosinophilic inclusions with pale halo in the hepatocytic cytoplasm, which can be identified by anti-fibrinogen immunohistochemical staining. The fingerprint-like structures under electron microscope are helpful for the diagnosis, while FGG sequencing detects the pathogenic mutation of exon 8 or 9 that can clearly explain the phenotype. However, the diagnosis of FSD cannot be completely ruled out if the relevant mutations are not detected.

Characteristics and Forensic Identification of Blunt Vertebral Artery Injury / 法医学杂志

Blunt vertebral artery injury occurs frequently in forensic practice. However, injuries of the vertebral artery are easily ignored or overlooked because of its relatively deep location. Through literatures review, this paper finds that the manners of blunt vertebral artery injury are varied and one or more injury mechanisms may be involved simultaneously. Patients often undergo immediate or delayed cerebral apoplexy as well as compression and injury of surrounding structures, due to direct injury or secondary aneurysm or dissection, resulting in disability or death. Diseases such as, vertebral atherosclerosis and dysplasia can increase the disability and death risk and the difficulty of forensic identification. In forensic identification, the details of the case should be considered. For cases of suspected vertebral artery injury, in addition to routine examination of intracranial segment, attention should be paid to the examination of extracranial segment. If conditions permit, angiography can be used prior to or during the autopsy to improve the identification efficiency and accuracy of opinions.

Susceptibility vessel sign in subacute stroke patients with large vessel occlusion / 北京大学学报(医学版)

OBJECTIVE@#To investigate the presentation of susceptibility vessel sign (SVS) in subacute stroke patients with large vessel occlusion.@*METHODS@#We collected consecutive stroke patients who were admitted to Peking University First Hospital from December 2017 to August 2019 retrospectively. Those who had intracranial large vessel occlusion and received sensitivity weighted imaging (SWI) within 3 to 14 days after stroke onset were included in our analysis. The diagnosis of large vessel occlusion was based on magnetic resonance angiography (MRA), CT angiography (CTA) or digital subtraction angiography (DSA). The demographic information, clinical characteristics and imaging results were obtained from medical record. The occurrence rates of SVS sign were compared between stroke patients with cardioembolism (CE) and large artery atherosclerosis (LAA). In the sensitivity analysis, we performed a subgroup analysis in those patients who received SWI within 7 to 14 days after stroke onset. We also compared the occurrence rate of SVS sign between the patients with and without atrial fibrillation.@*RESULTS@#A total of 51 patients, 19 females and 32 males, with an average age of (63.04±11.23) years were analyzed in this study. Compared with LAA group, the patients in CE group were older and more likely to have an atrial fibrillation (P < 0.05). There were no significant differences between the CE group and LAA group in gender, hypertension, diabetes, coronary heart disease, hyperlipidemia, smoking, or National Institute of Health stroke scale(NIHSS) score at admission. SVS sign was found in 30 patients. Of whom, 3 were in CE group and 27 in LAA group. The occurrence rate of SVS sign was higher in the LAA group than in the CE group significantly (65.9% vs. 30.0%, P=0.039). The subgroup analysis showed that, in the patients who received SWI examination within 7 to 14 days after stroke onset, the differences between the two groups were still statistically significant (0 vs. 72.7%, P=0.006). Another sensitivity analysis showed that, the rate of SVS in the patients with atrial fibrillation was significantly lower than those patients without atrial fibrillation (25% vs. 65.1%, P=0.043).@*CONCLUSION@#In subacute stroke patients, the occurrence rate of SVS sign in CE group was lower than that of LAA group. The significance of SVS sign in the differentiation of stroke subtype needs further validation.

Decitabine combined with arsenious acid in the treatment of patients with higher-risk myelodysplastic syndromes and chronic myelomonocytic leukemia / 中国实用内科杂志

OBJECTIVE: To evaluate the clinical efficacy of decitabine combined with arsenious acid in the treatment of patients with higher-risk myelodysplastic syndromes(MDS) and chronic myelomonocytic leukemia(CMML). METHODS: Totally 39 patients with MDS and 8 patients with CMML received the treatment of decitabine and arsenious acid from April 2016 to December 2018. Decitabine [20 mg/(m~2·d)] and arsenious acid [0.15 mg/(m~2·d)] were administered intravenously for 5 consecutive days every 4-6 weeks. Patients who achieved complete or partial remission entered into the consolidation cycle. Efficacy and influencing factor were analyzed. RESULTS: Clinical response were observed in 31 patients after a median of 2 courses(ranging 1-12) of treatment. The overall response rate(ORR) was 66.0%. The median duration of response was 16 weeks(ranging 2-52 weeks). There were 8 cases(17.0%) of complete remission(CR), 10 cases(21.3%) of partial remission(PR),12 cases(25.5%) of hematological improvement(HI), 1 case(2.1%) of marrow complete remission(mCR), 8 cases(17.0%) of stable disease(SD), and 1 case(2.1%) of progressive disease(PD). By next generation sequencing, 25 genes mutated with 70 times in 33 cases. The mutation frequency of epigenetic regulators(57.6%) was higher than splicing factors(33.5%), transcription factors and kinase signaling(54.5%),and TP53(21.2%)(P<0.01). There was no significant difference in response rates among these patients(47.4%, 54.5%, 50.0% and85.7%, P=0.977). Gene mutation frequency(VAF) of patients who responded to the regimen declined significantly(16.67% vs. 10.26%,P=0.014). CONCLUSION: Decitabine combined with arsenious acid has significant effect in the treatment of patients with higher-risk MDS and CMML and is well-tolerated. Gene mutation test results by next generation sequencing might be related to clinical response.

Effect of calcium dobesilate on fundus microcirculation in patients with diabetic retinopathy and cataract / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the effect of calcium dobesilate combined with hypoglycemics for patients with diabetic retinopathy (DR) and cataract, and the influence on microcirculation of eye fundus, hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) level. METHODS: Totally 98 DR patients with cataract (126 eyes) from January 2013 to December 2015 in our hospital were selected as the research objects, and were divided into two groups randomly(treatment group:64 eyes in 49 patients, control group: 62 eyes in 49 patients). The control group was treated with acarbose tablet and metformin, while treatment group was treated with calcium dobesilate additionally. The clinical effect, the glycemic control effect, serum HIF-1α and VEGF level, eye function and fundus microcirculation of two groups after 12mo were compared. RESULTS: After 12mo, the total effective rates of two groups were 87.5%,61.3% respectively, which indicated significantly difference (P<0.05); the vision of treatment group was significantly higher than that of control group (P<0.05). Two groups' blood glucose level decreased significantly, and no significant difference between two groups(P>0.05). After 1-month treatment, the plasma viscosity, erythrocyte aggregation index, erythrocyte deformability index, erythrocyte sedimentation rate and hematocrit in the treatment group were significantly lower than those in the control group (P<0.05). The PSV and EDV of the posterior ciliary artery and central artery in the treatment group were significantly higher than those in the control group (P<0. 05), and RI was significantly lower than that in the control group (P<0.05). After 12-month treatment, the HIF-1α level of two groups were 35 90士11.36mmol/L, 46.75士12.08mmol/L respectively;the VEGF of two groups level were 89.72士13.61mmol/L, 110.30士16.74mmol/L, respectively, the treatment group's HIF- 1α level and VEGF were significantly lower than control group (P<0.05), and both decreased significantly after treatment (P<0.05). CONCLUSION: Calcium dobesilate combined with hypoglycemics can effectively increase the clinical effect in the treatment of retinopathy diabetic cataract, effectively control blood glucose, improve microcirculation of eye fundus, decrease HIF - 1α, VEGF level, inhibit angiogenesis.

Current Status of Forensic Identification for Blunt Injuries of Internal Carotid Arterial System / 法医学杂志

Internal carotid arterial system is the main source of blood supply in brain. In forensic identi-fication practice, blunt injures of internal carotid arterial system usually cause complications such as throm-bus, aneurysm and arteriovenous fistula, etc. The deaths following delayed cerebral infarction or intracra-nial haemorrhage are not rare. At present, literature of deaths caused by blunt injuries of internal carotid arterial system mainly consist of case reports in China. This paper reviews related literature and case re-ports at home and abroad, and summarizes forensic medical features and identification method of the deaths caused by such injuries. The results show that blunt injures of internal carotid arterial system are related to the direct or indirect force on head and neck, which can result in exceed physiological range traction of head and neck, incision following basicranial fracture, etc. Such injuries are common in the cases as mechanical asphyxia, cervical manipulation, traffic accident and fall, etc. The artery should be examined carefully, and the relationship among injury, disease and death should be analysed correctly when no cause of infarction and hemorrhage was found in routine examination of such cases in forensic pratice. Because of the difficulty for exposing the artery completely in autopsy, angiography can be used to infer the location when necessary for improving the scientificity and reliability of the appraisal conclusion.

Clinical effect of anterior vitrectomy for congenital cataract / 国际眼科杂志(Guoji Yanke Zazhi)

?AlM: To evaluate the clinical efficacy of posterior continuous curvilinear capsulorhexis ( PCCC ) combined with anterior vitrectomy in preventing posterior capsule opacification of congenital cataract surgery. ?METHODS:Postoperative clinical follow-up data of 82 cases ( 87 eyes ) with congenital cataract treated in Eye Center of our hospital from January 2011 to August 2014 were retrospectively analyzed. The patients were divided into the surgical control group ( 38 cases, 40 eyes, recieved phacoemulsification + PCCC ) and the study group ( 44 cases, 47 eyes, accepted phacoemulsification+ PCCC + anterior vitrectomy). The incidence of central optic axis opaque and postoperative visual acuity distribution were recorded at 1a follow - up. lntraoperative and postoperative complications were observed. ?RESULTS:The rate of central optic axis opaque grade 0 in control group was 37. 5%, compared to 76. 6% in study groups. The opacity distribution ratio of grade 1,2,3 and 4 in study group were lower than that of control group, and the central optic axis opacity distribution ratio in study group was significantly better than that of control group (P0. 5 in control group was lower than the 40 eyes ( 85. 11%) of that in study group. The visual acuity between two groups has statistical significance difference after 1a follow-up ( P ?CONCLUSlON: Combination of phacoemulsification, PCCC and anterior vitrectomy presents reliable clinical effects on postoperative central optic axis opacity distribution ratio and visual acuity, and it should be adopted to prevent the occurrence of posterior capsule opacification.

Effect of triptolide on reversing hypermethylation of apc gene in Jurkat cells and its possible mechanisms / 中国实验血液学杂志

This study was aimed to investigate the effect of traditional Chinese medicine, Triptolide (TPL) on reversing hypermethylation of antioncogene (apc gene) in acute lymphoblastic leukemia cell line Jurkat in vitro and to explore its mechanisms. The effects of TPL on cell growth, proliferation and cell cycle were detected by growth curve, MTT assay, colony formation test and flow cytometry, respectively. The effect of TPL on apc gene methylation of Jurkat cells was analyzed by nested methylation specific PCR; the expressions of apc gene, dnnt3a, dnmt3b mRNA were measured by RT-PCR; the protein expression of apc gene was detected by Western blot. The results showed that as compared with untreated control cells, the TPL of different concentrations could significantly inhibit growth and proliferation of Jurkat cells in dose-and time-dependent manners with IC₅₀ 19.7 ng/ml at 48 hours. All cytosines in CpG dinucleotides in untreated Jurkat cells had no changed, while all cytosines in Jurkat cells treated with TPL had been converted to thymidine suggesting the methylation of apc gene in Jurkat cells. The TPL could reverse hypermethylation of apc gene and induced the mRNA and protein expression of apc gene in dose-dependent manner. It is concluded that the small dose of TPL can obviously suppress the proliferation of Jurkat cells, activate and up-regulate the expression of apc gene through demethylation of apc gene resulting from DNMT and/or direct action, thereby inhibit the proliferation rate of Jurkat cells.

Detection of APC gene promoter methylation in hematological malignant cell lines by nested-methylation specific polymerase chain reaction / 中国实验血液学杂志

This study was aimed to investigate the efficiency of nested methylation specific polymerase chain reaction (nMS-PCR) for detecting the APC gene promoter methylation and to clarify the roles of methylation in genesis and development of hematologic malignancies, as well as to screen the hematologic malignant cell lines with hypermethylation of APC gene promoter to use as an ideal cell model for exploring the relationship between gen methylation and gene expression. The genome DNA of 10 cell lines modified with bisulfide was amplified and the methylation status of APC gene promoter was detected by using nMS-PCR. The results showed that the methylation of APC gene promoter was detected in Jurkat cells, while could not be detected in CA46, U266, Molt4, K562, HL-60, CEM, AKR, U937 and Raji cell lines. In conclusion, APC gene methylation in hematological malignant cell lines can be accurately detected by nMS-PCP method, which is simple method for detecting methylation status of various hematological malignant cell lines.

Methylation status of CpG islands in secreted frizzled-related protein gene promoter region of malignant hematopoietic cell lines / 中国实验血液学杂志

To investigate the methylation status of CpG islands of the secreted frizzled-related protein (SFRP) gene promoter region in malignant hematopoietic cell lines, and to explore the possible relationship of CpG abnormal methylation status with pathogenic mechanism of hematologic malignancies. Methylation-specific PCR was used to detect the status of SFRP gene promoter region in nine malignant hematopoietic cell lines and peripheral blood mononuclear cells from healthy people. The results indicated that hypermethylation of 2 genes coding for SFRP1 and 2 were present in nine malignant hematopoietic cell lines, however, methylation and unmethylation of SFRP4 were both detected in CA46, HL60 and U937 cell lines, and SFRP5 in U266 as well. None of the normal mononuclear cells showed methylation of SFRP 1-5 genes. It is concluded that the hypermethylation of SFRP genes is related to the evolution of malignant hematopoiesis. Methylation of SFRP genes may serve as potential independent biomarkers for early detection of hematologic malignancies.