Dynamic observation on capillarization of liver sinusoidal endothelial cells induced by Echinococcus multilocularis infection / 中国血吸虫病防治杂志

Objective To investigate the capillarization of liver sinusoidal endothelial cells (LSECs) and its association with hepatic fibrosis during the development of alveolar echinococcosis, so as to provide the basis for unraveling the mechanisms underlying the role of LSEC in the development and prognosis of hepatic injuries and hepatic fibrosis caused by alveolar echinococcosis. Methods Forty C57BL/6 mice at ages of 6 to 8 weeks were randomly divided into a control group and 1-, 2- and 4-week infection groups, of 10 mice in each group. Each mouse in the infection groups was intraperitoneally injected with 2 000 Echinococcus multilocularis protoscoleces, while each mouse in the control group was given an equal volume of phosphate-buffered saline using the same method. All mice were sacrificed 1, 2 and 4 weeks post-infection and mouse livers were collected. The pathological changes of livers were observed using hematoxylin-eosin (HE) staining, and hepatic fibrosis was evaluated through semi-quantitative analysis of Masson’s trichrome staining-positive areas. The activation of hepatic stellate cells (HSCs) and extracellular matrix (ECM) deposition were examined using immunohistochemical staining of α-smooth muscle actin (α-SMA) and collagen type I alpha 1 (COL1A1), and the fenestrations on the surface of LSECs were observed using scanning electron microscopy. Primary LSECs were isolated from mouse livers, and the mRNA expression of LSEC marker genes Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf was quantified using real-time fluorescence quantitative PCR (qPCR) assay. Results Destruction of local liver lobular structure was observed in mice 2 weeks post-infection with E. multilocularis protoscoleces, and hydatid cysts, which were surrounded by granulomatous tissues, were found in mouse livers 4 weeks post-infection. Semi-quantitative analysis of Masson’s trichrome staining showed a significant difference in the proportion of collagen fiber contents in mouse livers among the four groups (F = 26.060, P < 0.001), and a higher proportion of collagen fiber contents was detected in mouse livers in the 4-week infection group [(11.29 ± 2.58)%] than in the control group (P < 0.001). Immunohistochemical staining revealed activation of a few HSCs and ECM deposition in mouse livers 1 and 2 weeks post-infection, and abundant brown-yellow stained α-SMA and COL1A1 were deposited in the lesion areas in mouse livers 4 weeks post-infection, which spread to surrounding tissues. Semi-quantitative analysis revealed significant differences in α-SMA (F = 7.667, P < 0.05) and COL1A1 expression (F = 6.530, P < 0.05) in mouse levers among the four groups, with higher α-SMA [(7.13 ± 3.68)%] and COL1A1 expression [(13.18 ± 7.20)%] quantified in mouse livers in the 4-week infection group than in the control group (both P values < 0.05). Scanning electron microscopy revealed significant differences in the fenestration frequency (F = 37.730, P < 0.001) and porosity (F = 16.010, P < 0.001) on the surface of mouse LSECs among the four groups, and reduced fenestration frequency and porosity were observed in the 1-[(1.22 ± 0.48)/μm2 and [(3.05 ± 0.91)%] and 2-week infection groups [(3.47 ± 0.10)/μm2 and (7.57 ± 0.23)%] groups than in the control group (all P values < 0.001). There was a significant difference in the average fenestration diameter on the surface of mouse LSECs among the four groups (F = 15.330, P < 0.001), and larger average fenestration diameters were measured in the 1-[(180.80 ± 16.42) nm] and 2-week infection groups [(161.70 ± 3.85) nm] than in the control group (both P values < 0.05). In addition, there were significant differences among the four groups in terms of Stabilin-1 (F = 153.100, P < 0.001), Stabilin-2 (F = 57.010, P < 0.001), Ehd3 (F = 31.700, P < 0.001), CD209b (F = 177.400, P < 0.001), GATA4 (F = 17.740, P < 0.001), and Maf mRNA expression (F = 72.710, P < 0.001), and reduced mRNA expression of Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf genes was quantified in three infection groups than in the control group (all P values < 0.001). Conclusions E. multilocularis infections may induce capillarization of LSECs in mice, and result in a reduction in the expression of functional and phenotypic marker genes of LSECs, and capillarization of LSECs occurs earlier than activation of HSC and development of hepatic fibrosis.

SRF-rearranged cellular perivascular myoid tumor: a clinicopathological analysis of two cases / 中华病理学杂志

Objective: To investigate the clinicopathological features, immunophenotype, diagnosis and differential diagnosis of SRF-rearranged cellular perivascular myoid tumor. Methods: Two cases of SRF-rearranged cellular perivascular myoid tumor diagnosed in the Department of Pathology, Fudan University Shanghai Cancer Center from October 2021 to March 2022 were collected. Immunohistochemical staining, fluorescence in-situ hybridization (FISH) and next-generation sequencing (NGS) were performed, and the literature was reviewed. Results: Case 1, a 3-month-old boy presented with a painless tumor of the scalp, measuring about 2 cm in diameter. Case 2, a 3-year-old girl complained with a painless tumor of the knee, measuring approximately 1.5 cm in diameter. Microscopically, the tumor had a clear boundary and showed multinodular growth. The tumor was mainly composed of spindle cells arranged in long intersecting fascicles associated with thin, slit-like or branching ectatic vessels, focally forming hemangiopericytoma-like appearance. The tumor cells were abundant, but there was no obvious atypia. Mitotic figures (3-4/10 HPF) were noted. H-caldesmon and SMA were positive in both cases. Case 1 showed diffuse and strong positivity for Desmin, and focally for CKpan. Ki-67 proliferation index was 20% and 30%, respectively. FISH displayed NCOA2 gene translocation in case 1 and the RELA gene translocation in case 2. NGS detected the SRF-NCOA2 gene fusion in case 1 and the SRF-RELA gene fusion in case 2. Both patients underwent local excisions. During the follow-up of 5-14 months, case 1 had no local recurrence, while case 2 developed local recurrence 1 year post operatively. Conclusions: SRF-rearranged cellular perivascular myoid tumor is a novel variant of perivascular cell tumor, which tends to occur in children and adolescents. The tumor forms a broad morphologic spectrum ranging from a pericytic pattern to a myoid pattern, and include hybrid tumors with a mixture of pericytic and myoid patterns. Due to its diffuse hypercellularity and increased mitotic figures and smooth muscle-like immunophenotype, the tumor is easy to be misdiagnosed as myogenic sarcomas. The tumor usually pursues a benign clinical course and rare cases may locally recur.

Application progress of swept-source optical coherence tomography angiography in ophthalmology / 国际眼科杂志(Guoji Yanke Zazhi)

Swept-source optical coherence tomography angiography(SS-OCTA)is a new vascular imaging technique that was recently proposed. It has the advantages of being non-invasive, quick, high-resolution, and automated vascular stratification imaging. It is extremely helpful in the early diagnosis of ophthalmology-related diseases, as well as in the evaluation of treatment effectiveness and the tracking of disease progression. Based on the foundation of OCTA, SS-OCTA utilizes a fast-tuning laser with a wavelength of 1 050 nm for deeper penetration and non-invasive depth-resolved imaging of the retinal and choroidal microvascular systems, deepening the understanding of the characteristics of a wide range of ophthalmic diseases(fundus lesions, glaucoma, neurodegenerative diseases, etc.). The structures of the anterior segment of the eye can also be studied using SS-OCTA, including changes in the depth and density of corneal neovascularization as well as changes in iris neovascularization before and after therapy. This approach provides a novel tool for ophthalmic clinical practice. The development of the clinical use of SS-OCTA technology in ophthalmology is reviewed in this article.

Advances in clinical research on drug-induced acute interstitial nephritis / 中国临床药理学与治疗学

The kidneys are one of the main excretory organs for drugs and when drugs are not excreted effectively, they can accumulate in the kidneys or in the interstitial tubules, leading to drug-induced kidney injury. The tubulointerstitium accounts for 80% of the volume of the kidney and is the primary site of response to various types of renal injury. This article focuses on drug-induced acute interstitial nephritis, highlighting its clinical symptoms, listing common induction drugs, analysing pathological features, and explaining its pathogenesis from the perspective of immune response, with the aim of providing a basic and clinical evidence for subsequent studies.

Effect of NMDA receptor blocker in relieving HIV-1/gp120 induced learning and memory disorder in rats and its mechanism / 中国药理学通报

Aim: To investigate the alleviating effect of NMDA receptor blocking on learning and memory impairment induced by gp120 in rats and its mechanism. Methods: (1 ) Thirty-two SD rats were randomly divided into control group, sham operation group, gpl20 group, and gp120 + Memantine group. Except for the control group, the other groups underwent a bilateral hippocampal injection to establish the model of learning and memory impairment in rats. Memantine (10 mg • kg

Effect of astaxanthin on blood brain barrier injury and cognitive impairment in db/db mice and its mechanism / 中国药理学通报

Aim To investigate the effect of astaxanthin (ASTA) on the blood brain barrier (BBB) injury and cognitive disorders in mice induced by hyperglycemia and the possible mechanism. Methods db/db mice aged eight weeks were administered ASTA (5, 10, 20 mg • kg

Practice and Thinking of Promoting Spiritual Culture Cultivation by Inheriting the Red Gene in Public Hospital / 中国医学伦理学

The red gene is the crystallization of the ideas and wisdom of the Chinese Communist Party’s century-long struggle, and plays an irreplaceable and decisive role in cultivating socialist hospital culture and medical professionals in the new era. The Chinese Academy of Medical Science (CAMS) Cancer Hospital has a distinctive red gene trait. For more than 60 years since its establishment, through the protection of the red gene inheritance carrier, the enrichment of the content and expression form of the red gene inheritance, and the exploration and demonstration of the role model in the red gene inheritance, it has always integrated the red gene inheritance into the whole process of hospital construction, development and spiritual culture cultivation, and has achieved remarkable results, accumulated rich practical experience, and provided a useful reference for the spiritual and cultural construction of public hospitals.

Visual analysis of social isolation studies on adolescents based on Web of Science / 上海预防医学

ObjectiveTo perform visual analysis of the literature in the field of adolescent social isolation in order to provide reference for research on social isolation of Chinese teenagers. MethodsLiterature related to adolescent social isolation was retrieved from the Web of Science core collection database from September 2013 to September 2022. CiteSpace 6.1.R3 software was used to conduct bibliometric analysis on publication volume， publication organization， keyword clustering， keyword salience， and time⁃line map of hot words. ResultsA total of 1 347 related articles were screened out， and the overall number of publications from 2013 showed an upward trend. The largest number of articles came from the United States with 521 （38.68%）， and China ranked 6th with 79 （5.86%）. The top three institutions were Columbia University in the United States （29 articles）， King's College London in the United Kingdom （28 articles） and the University of London in the United Kingdom （27 articles）. Research hotspots mainly focused on social isolation， physical and mental health， loneliness， quality of life and comprehensive interventions. ConclusionIn recent years， the problem of adolescent social isolation has attracted continuous attention from foreign scholars. Based on our national conditions， we should conduct relevant screening and preventive assessment for social isolation of special youth groups， so as to conduct early management and intervention.

Identification of Complex and Combined Antibody Consisted of Anti-c, Anti-E, Anti-Jka and Anti-Fya / 中国实验血液学杂志

OBJECTIVE@#To investigate the role of multiple serological methods in the identification of complex antibodies.@*METHODS@#The blood group antigens were detected by saline and microcolumn agglutination methods. The saline method was used to screen and identify IgM-type antibodies in the patient's serum, while the polybrene, anti-globulin, microcolumn agglutination, enzymic and absorption-elution methods were used to screen and identify IgG-type antibodies.@*RESULTS@#The patient was B/CCDee/Jk(a-b+)/Fy(a-b+) blood type. The serum reacted with panel cells, and the reaction presented anti-E pattern in the saline medium. It was fully positive in the microcolumn agglutination card, except 2 negative ones after using papain to treat the panel cells. Referring to the pattern table, it was concluded that there existed anti-c, anti-E, and anti-Jka antibodies, and one antibody corresponding to an antigen that was easily destroyed by papain. The red blood cells with specific phenotype were selected for absorption-elution to identify IgG-type anti-c, anti-E, anti-Jka and anti-Fya antibodies.@*CONCLUSION@#It is confirmed that IgM-type anti-E, and IgG-type anti-c, anti-E, anti-Jka and anti-Fya antibodies exist in the patient's serum by multiple serological methods.

Application of metagenomic next-generation sequencing of bronchoalveolar lavage fluid in the diagnosis and treatment of refractory pneumonia in children / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical application of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) in the etiological diagnosis and treatment of refractory pneumonia (RTP) in children.@*METHODS@#A retrospective analysis was performed on 160 children with RTP who were admitted to the Department of Pediatric Internal Medicine, Maternal and Child Health Hospital of Inner Mongolia Autonomous Region, from January 2020 to March 2023. According to whether mNGS was performed, they were divided into two groups: mNGS (n=80) and traditional testing (n=80). All children received the tests of inflammatory markers and pathogen tests after admission. Traditional pathogenicity tests included microbial culture (sputum specimen collected by suction tube), nucleic acid detection of respiratory pathogens, and serological test (mycoplasma, tuberculosis, and fungi). For the mNGS group, BALF specimens were collected after bronchoscopy and were sent to the laboratory for mNGS and microbial culture. The two groups were analyzed and compared in terms of the detection of pathogens and treatment.@*RESULTS@#Compared with the traditional testing group, the mNGS group had a significantly higher detection rate of pathogens (92% vs 58%, P<0.05), with more types of pathogens and a higher diagnostic rate of mixed infections. Compared with the traditional testing group, the mNGS group had a significantly higher treatment response rate and a significantly lower incidence rate of complications during hospitalization (P<0.05). Treatment was adjusted for 68 children in the mNGS group according to the results of mNGS, with a treatment response rate of 96% (65/68) after adjustment.@*CONCLUSIONS@#Compared with traditional pathogen tests, BALF mNGS can significantly improve the detection rate of pathogens and find some rare pathogens. In clinical practice, when encountering bottlenecks during the diagnosis and treatment of children with RTP, it is advisable to promptly perform the mNGS to identify the pathogens.

Effectiveness of sagittal top compression reduction technique in treatment of thoracolumbar vertebral fractures / 中国修复重建外科杂志

OBJECTIVE@#To investigate the effectiveness of sagittal top compression reduction technique in the treatment of thoracolumbar vertebral fractures.@*METHODS@#A retrospective analysis was conducted on the clinical data of 59 patients with thoracolumbar vertebral fractures who met the selection criteria and were admitted between November 2018 and January 2022. Among them, 34 patients were treated with sagittal top compression reduction technique (top pressure group), and 25 patients were treated with traditional reduction technique (traditional group). There was no significant difference in baseline data between the two groups ( P>0.05), including gender, age, fracture segment, cause of injury, AO classification of thoracolumbar vertebral fractures, thoracolumbar injury classification and severity (TLICS) score, American Spinal Injury Association (ASIA) grading, surgical approach, preoperative vertebral body index, height ratio of the anterior margin of injured vertebra, injured vertebra angle, segmental kyphosis angle, visual analogue scale (VAS) score, and Oswestry disability index (ODI). The operation time, intraoperative blood loss, and incidence of complications between the two groups were recorded and compared. After operation, VAS score and ODI were used to evaluate effectiveness, and X-ray and CT examinations were performed to measure imaging indicators such as vertebral body index, height ratio of the anterior margin of injured vertebra, injured vertebra angle, and segmental kyphosis angle.@*RESULTS@#There was no significant difference in operation time and intraoperative blood loss between the two groups ( P>0.05). No complication such as dural sac, nerve root, or vascular injury was found during operation, and all incisions healed by first intention. Patients in both groups were followed up 6-48 months, with an average of 20.6 months. No loosening, breakage, or failure of internal fixation occurred during follow-up. The imaging indicators, VAS score, and ODI of the two groups significantly improved at 1 week and last follow-up when compared to preoperative ones ( P<0.05). At last follow-up, the VAS score and ODI further significantly improved when compared to 1 week after operation ( P<0.05). At 1 week after operation and last follow-up, the vertebral body index, segmental kyphosis angle, injured vertebra angle, and ODI in the top pressure group were significantly better than those in the traditional group ( P<0.05). There was no significant difference in VAS score and height ratio of the anterior margin of injured vertebra between the two groups at 1 week after operation ( P>0.05), but the two indicators in the top pressure group were significantly better than those in the traditional group at last follow-up ( P<0.05).@*CONCLUSION@#The treatment of thoracolumbar vertebral fractures with sagittal top compression reduction technique can significantly improve the quality of vertebral reduction, and is superior to traditional reduction techniques in relieving pain and improving spinal function.

Component profile analysis of Sanhan Huashi Formula based on UHPLC-LTQ-Orbitrap-MS, GC-MS, and UHPLC-QQQ-MS/MS / 中国中药杂志

This study comprehensively analyzed the active components of Sanhan Huashi Formula using qualitative and quantitative mass spectrometry techniques, laying the foundation for understanding its pharmacological substance basis. UHPLC-LTQ-Orbitrap-MS and GC-MS technologies were used to analyze and identify the volatile and non-volatile components in Sanhan Huashi Formula. UHPLC-QQQ-MS/MS technology was used to simultaneously determine the content of 27 major active components in the formula. The results showed that 308 major chemical components were identified in Sanhan Huashi Formula, among which 60 compounds were identified by comparing with reference standards, mainly including alkaloids, flavonoids, coumarins, triterpenoid saponins, amino acids, and nucleosides. GC-MS technology preliminarily identified 52 volatile compounds, with γ-eudesmol and β-eudesmol as the main components. The quantitative results demonstrated good linearity(r>0.99) for the 27 active components, indicating the stability, simplicity, and reliability of the established method. Among them, amygdalin, nodakenin, arecoline, ephedrine, and pseudoephedrine had relatively high content and were presumably the main pharmacologically active substances. In conclusion, this study systematically and comprehensively characterized the major chemical components and patterns in Sanhan Huashi Formula, providing a basis for understanding its pharmacological mechanisms and clinical applications.

Study on biomarkers of acteoside in treating puromycin aminonucleoside nephropathy in young rats based on non-targeted urine metabolomics technology / 中国中药杂志

This study aims to reveal the endogenous metabolic characteristics of acteoside in the young rat model of purinomycin aminonucleoside nephropathy(PAN) by non-targeted urine metabolomics and decipher the potential mechanism of action. Biochemical indicators in the urine of rats from each group were determined by an automatic biochemical analyzer. The potential biomarkers and related core metabolic pathways were identified by ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) combined with principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). MetaboAnalyst 5.0 was used to establish the receiver operating characteristic(ROC) curve for evaluating the clinical diagnostic performance of core metabolites. The results showed that acteoside significantly decreased urinary protein-to-creatinine ratio in PAN young rats. A total of 17 differential metabolites were screened out by non-targeted urine metabolomics in PAN young rats and they were involved in phenylalanine metabolism and phenylalanine, tyrosine and tryptophan biosynthesis. Thirtten differential metabolites were screened by acteoside intervention in PAN young rats, and they were involved in phenylalanine metabolism and arginine and proline metabolism. Among them, leucylproline and acetophenone were the differential metabolites that were significantly recovered after acteoside treatment. These pathways suggest that acteoside treats PAN in young rats by regulating amino acid metabolism. The area under the curve of two core biomarkers, leucylproline and acetophenone, were both greater than 0.9. In summary, acteoside may restore amino acid metabolism by regulating endogenous differential metabolites in PAN young rats, which will help to clarify the mechanism of acteoside in treating chronic glomerulonephritis in children. The characteristic biomarkers screened out have a high diagnostic value for evaluating the treatment of chronic glomerulonephritis in children with acteoside.

Evaluation of Chinese Food Guide Pagoda (2022) / 环境与职业医学

Background A rational diet is the foundation of health. Dietary guidelines for Chinese residents and Chinese Food Guild Pagoda aim to provide healthy eating guidance for Chinese residents. Objective To evaluate the rationality and applicability of the "Chinese Food Guild Pagoda" (2022). Methods The energy and nutrient supplies of foods recommended by the Food Pagoda-were calculated based on the chinese food composition Table. The degree of requirement satisfaction for energy or nutrients was calculated by comparing with the recommended nutrient intake (RNI) or adequate intake (AI) for adults (≥ 18 years) with light physical activity according to the Chinese dietary reference intakes. Results The estimated energy intake was 46662.79-10062.28 kJ, which met the 6697.36-10046.04 kJ set by the Food Pagoda. We estimated that 65.74-102.78 g of protein, 59.67-82.71 g of fat, and 211.27-333.19 g of carbohydrate were provided by following the Food Pagoda. Adequate vitamins and minerals were also provided by following the Food Pagoda. However, the amounts of vitamin E was estimated to be 2.40-3.28 times and sodium was 1.59-1.75 times of AI, while selenium was 63.40%-98.15% of RNI. Conclusion The amounts of vitamin E and sodium by following the Food Pagoda may be higher and selenium may be lower than recommended intakes. Energy and other nutrients in the Food Pagoda are suitable for general adults in China.

Serum concentrations of perfluoroalkyl and polyfuoroalkyl substances and determinants in men of childbearing age / 环境与职业医学

Background Perfluoroalkyl and polyfluoroalkyl substances (PFASs) exposure may affect male reproductive health. There are regional differences in PFASs exposure levels among men of childbearing age in China, and current research results on associated influencing factors are inconsistent. Objective To investigate the levels of PFASs in serum and their determinants among men of childbearing age. Methods The participants (n=113, 22-45 years old) were from a cross-sectional study of exposure to environmental pollutants and male reproductive health damage in Hubei Province conducted from April to June 2013 at the Reproductive Medicine Center of Tongji Hospital, Wuhan, Hubei Province. Eleven kinds of PFASs were measured in serum by isotopic dilution-high performance liquid chromatography-tandem mass spectrometry. The included PFASs were prefluorohexanoic acid (PFHxA), perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUdA), perfluorododecanoic acid (PFDoA), perfluorotridecanoic acid (PFTrDA), perfluorotetradecanoic acid (PFTeDA), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS). Information about participants' demographic characteristics, lifestyle, and habits was collected by a set of self-designed questionnaires. The associations of demographic characteristics, lifestyle, and habits with exposure to PFASs were analyzed by linear regression. Results The major components of PFASs were PFOS and PFOA, and the concentrations expressed as M (P25, P75) were 8.31 (4.90, 17.79) ng·mL−1 and 2.77 (2.18, 3.46) ng·mL−1, respectively. The positive rates of six PFASs (PFOA, PFNA, PFDA, PFUdA, PFHxS, and PFOS) were 100%, followed by PFDoA and PFTrDA (87.61% and 88.59%, respectively). The linear regression results showed that age was positively associated with the levels of Σ8PFASs (sum of the concentrations of the eight PFASs with a positive rate greater than 80%) (P < 0.05). The concentration of serum PFOA in men with monthly family income of 2000-4000 yuan was 53.73% (P < 0.01) higher than those in men with monthly family income of <2000 yuan. The serum concentrations of PFNA and PFTrDA were both 32.31% (P < 0.05) higher in men with monthly family income ≥4000 yuan than those in men with monthly family income <2000 yuan. The serum concentration of PFHxS in men who used plastic cups was 33.64% (P < 0.01) higher than that in men who did not report oral contact with plastic products (plastic tableware, plastic cups, and plastic bags for packing food). The serum concentrations of PFHxS, PFOS, and Σ8PFASs were 33.64% (P < 0.01), 43.33% (P < 0.01), and 36.34% (P < 0.05) higher in men who bathed with laundry soap than those in men who did not use detergents. Men who bathed with toilet soap had a 34.99% (P < 0.05) higher serum concentration of PFHxS than those who bathed without detergents. Conclusion Men of childbearing age are exposed to PFASs extensively. Age, monthly household income, usage of laundry soap or toilet soap in bathing, and usage of plastic cups may influence the level of PFASs in serum. However, further investigation is needed to confirm these results.

Resolving the lineage relationship between malignant cells and vascular cells in glioblastomas

Glioblastoma multiforme (GBM), a highly malignant and heterogeneous brain tumor, contains various types of tumor and non-tumor cells. Whether GBM cells can trans-differentiate into non-neural cell types, including mural cells or endothelial cells (ECs), to support tumor growth and invasion remains controversial. Here we generated two genetic GBM models de novo in immunocompetent mouse brains, mimicking essential pathological and molecular features of human GBMs. Lineage-tracing and transplantation studies demonstrated that, although blood vessels in GBM brains underwent drastic remodeling, evidence of trans-differentiation of GBM cells into vascular cells was barely detected. Intriguingly, GBM cells could promiscuously express markers for mural cells during gliomagenesis. Furthermore, single-cell RNA sequencing showed that patterns of copy number variations (CNVs) of mural cells and ECs were distinct from those of GBM cells, indicating discrete origins of GBM cells and vascular components. Importantly, single-cell CNV analysis of human GBM specimens also suggested that GBM cells and vascular cells are likely separate lineages. Rather than expansion owing to trans-differentiation, vascular cell expanded by proliferation during tumorigenesis. Therefore, cross-lineage trans-differentiation of GBM cells is very unlikely to occur during gliomagenesis. Our findings advance understanding of cell lineage dynamics during gliomagenesis, and have implications for targeted treatment of GBMs.

Advances in the diagnosis and treatment of phosphomannomutase 2 deficiency / 中国当代儿科杂志

Phosphomannomutase 2 deficiency is the most common form of N-glycosylation disorders and is also known as phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG). It is an autosomal recessive disease with multi-system involvements and is caused by mutations in the PMM2 gene (OMIM: 601785), with varying severities in individuals. At present, there is still no specific therapy for PMM2-CDG, and early identification, early diagnosis, and early treatment can effectively prolong the life span of pediatric patients. This article reviews the advances in the diagnosis and treatment of PMM2-CDG.

Application value of CNV-seq for the prenatal diagnosis of women with high-risk pregnancies / 中华医学遗传学杂志

OBJECTIVE@#To assess the application value of copy number variation sequencing (CNV-seq) for women with a high risk for fetal anomalies.@*METHODS@#Based on the results of non-invasive prenatal testing (NIPT), 271 high-risk pregnant women were divided into NIPT positive group (n = 83) and other anomaly group (advanced age, high risk by serological screening, repeated NIPT failure, adverse pregnancy history, abnormal ultrasound finding, and abnormal phenotype) (n = 188). CNV-seq was carried out to detect copy number variations (CNVs) in amniocytic DNA from the two groups of pregnant women, and karyotyping analysis of the amniotic cells was carried out for verification and comparison.@*RESULTS@#The amniocytes from 271 pregnant women were detected. The detection rate was 20.66% (56/271) for pathogenic CNVs by CNV-seq and 19.19% (52/271) for pathogenic karyotypes by karyotyping analysis. The difference was statistically significant (P < 0.05). CNV-seq had shown that, compared with NIPT positive group, the detection rates for likely pathogenic CNVs and variants of unknown significance (VUS) in other abnormality group were significantly higher [2.41%(2/83) vs. 5.32%(10/188)](P < 0.05).@*CONCLUSION@#CNV-seq can well suit the first-tier diagnosis for pregnant women suspected for fetal abnormality. In prenatal diagnosis settings, CNV-seq can identify additional and clinically significant cytogenetic abnormalities. In those with other abnormalities, the detection rates for likely pathogenic CNVs and VUS are higher than with the NIPT positive cases.

Tissue distribution of Qingfei Paidu Decoction based on HPLC-MS/MS / 中国中药杂志

The tissue distribution of Qingfei Paidu Decoction was studied by HPLC-MS/MS in vivo. Hypersil GOLD C_(18) column(2.1 mm×50 mm, 1.9 μm) was used for gradient elution with acetonitrile as the mobile phase A and 0.1% formic acid solution as the mobile phase B. High-resolution liquid chromatography-mass spectrometry in both positive and negative ion scanning mode and multiple response monitoring(MRM) mode was employed to analyze the behaviors of the active components of Qingfei Paidu Decoction in diffe-rent tissues. The results showed that 19, 9, 17, 14, 22, 19, 24, and 2 compounds were detected in plasma, heart, liver, spleen, lung, kidney, large intestine, and brain, respectively. The compounds belonged to 8 groups, covering 14 herbs in the prescription. After administration with Qingfei Paidu Decoction, the compounds were rapidly distributed in various tissues, especially in the lung, liver, large intestine, and kidney. The majority of the compounds displayed secondary distribution. This study comprehensively analyzed the distribution rules of the main active components in Qingfei Paidu Decoction and provided a basis for the clinical application.

EWSR1-SMAD3 positive fibroblastic tumor: a clinicopathological analysis / 中华病理学杂志

Objective: To investigate the clinicopathological features, immunophenotypes and molecular genetics of EWSR1-SMAD3 positive fibroblastic tumor (ESFT) with an emphasis on differential diagnosis. Methods: The clinicopathological data, immunohistochemical profiles and molecular profiles of 3 ESFT cases diagnosed at the Department of Pathology, Fudan University Shanghai Cancer Center from 2018 to 2021were analyzed. The related literature was also reviewed. Results: There were two males and one female. The patients were 24, 12 and 36 years old, respectively. All three tumors occurred in the subcutis of the foot with the disease duration of 6 months to 2 years. The tumors were presented with a slowly growing mass or nodule, accompanied with pain in 1 patient. The tumors ranged in size from 0.1 to 1.6 cm (mean, 1.0 cm). Microscopically, the tumors were located in the subcutaneous tissue with a nodular or plexiform growth pattern. They were composed of cellular fascicles of bland spindle cells with elongated nuclei and fine chromatin. One of the tumors infiltrated into adjacent adipose tissue. There was no nuclear atypia or mitotic activities. All three tumors showed prominent stromal hyalinization with zonal pattern present in one case. Focal punctate calcification was noted in two cases. The immunohistochemical studies showed that tumor cells were diffusely positive for ERG and negative for CD31 and CD34, with Ki-67 index less than 2%. Fluorescence in situ hybridization on the two tested cases identified EWSR1 gene rearrangement. The next generation sequencing analysis demonstrated EWSR1-SMAD3 fusion in all three cases. During the follow up, one patient developed local recurrence 24 months after the surgery. Conclusions: ESFT is a benign fibroblastic neoplasm and has a predilection for the foot, characterized by ERG immunoreactivity and EWSR1-SMAD3 fusion. Local recurrence might occur when incompletely excised. Familiarity with its clinicopathological features is helpful in distinguishing it from other spindle cell neoplasms that tend to occur at acral sites.