Objective To investigate the pathogenic mutations of BRCA1 and BRCA2 in patients with early-onset breast cancer(≤35 years) and explore the relationships between BRCA1/2 mutations and clinical features.Methods Seventy-four patients with early-onset breast cancer were enrolled,who were treated in Hospital 307 between September 2014 and June 2016.High-throughput sequencing was used to test the 49 exon sequences and adjacent sequences of BRCA1 and BRCA2.χ2 test was used to analyze the distribution of BRCA1/2 pathogenic mutations in each group that was set up according to clinical features.Results Fifteen mutations(20.27%) were identified,including 5(6.76%) in BRCA1 and 10(13.51%) in BRCA2.Eleven new pathogenic mutations were discovered,and BRCA1:c.5470_5477delTGCCCAAT was found in one patient.The frequency of BRCA1/2 mutations in the group with a family history of breast cancer or ovarian cancer was higher than in the group without a family history (40.91% vs 11.54%) (χ2=6.534,P=0.011).Conclusion BRCA1/2 pathogenic mutation is significant for early-onset breast cancer,especially for those with a family history of breast or ovarian cancer.The new mutations may be specific to Chinese people.BRCA1:c.5470_5477delTGCCCAAT may be the ancestor mutation among the Chinese.

Objective To investigate the 7 kinds of respirovirus etiology of children with acute respiratory infection(ARI) in Wenzhou area from 2005 to 2006.Methods Three thousand nine hundred and seventy children with ARI visited the Yuying children's hospital were chosen,including 308 children with acute upper respiratory infection(URI) and 3 662 children with lower respiratory infection(LRI).Direct immunofluorescence(DIF) was used to detect the respiratory syncytial virus(RSV),adenovirus(ADV),influenza virus(IV) A and B,parainf-luenza virus(PIV) type 1,2,3 from nasopharyngeal secretions(NPS) collected from these patients.Results Among the 3 970 samples,1 773(44.7%) positive results were determined and the positive rate of RSV(36.2%) was the highest.The isolating rate of respirovirus were all conspicuous difference in sex(?2=9.2 P

To identify the active constituents in vitro and blood-absorbed ingredients in vivo from Yin Chen Hao decoction provides scientific evidence for probing its prevention and treatment mechanism on acute liver injury. An ultrahigh performance liquid chromatography quadrupole-time of flight-mass spectrometry (UPLC-QTOF/MS) method was applied for analysis of Yin Chen Hao decoction and the serum samples of mice with con-A induced acute liver injury after preventive oral administration for 14 days (the use of all laboratory animals in this study was approved by the Ethics Committee of the Naval Medical University, 19YF1459400). A total of 90 chemical constituents were identified from Yin Chen Hao decoction, mainly were flavonoids, terpenoids, tannins, quinones. 5 prototype compounds were identified in the serum, including chrysophanol, deoxyrhapontin-8-O-gallate, mussaenosidic acid, herniarin, emodin. The established UPLC-QTOF/MS method could efficiently and sensitively identify the constituents in vitro and blood-absorbed ingredients of Yin Chen Hao decoction, primarily clarify the material basis of its hepatoprotective effect, and provided a scientific basis for the quality marker selection and the pharmacodynamic material basis research on the decoction.

AIM To evaluate the quality of Beidougen Formula Granules.METHODS Fifteen batches of standard decoctions and three batches of formula granules were prepared,after which paste rate and contents,transfer rates of magnoflorine,daurisoline,dauricine were determined.HPLC specific chromatograms were established,and cluster analysis was adopted in chemical pattern recognition.RESULTS For three batches of formula granules,the paste rates were 15.1%-16.6%,the contents of magnoflorine,daurisoline,dauricine were 18.93-19.39,9.42-9.60,6.79-6.85 mg/g with the transfer rates of 34.42%-35.25%,43.81%-44.65%,27.27%-27.51%from decoction pieces to formula granules,respectively,and there were seven characteristic peaks in the specific chromatograms with the similarities of more than 0.95,which demonstrated good consistence with those of standard decoctions and accorded with related limit requirements.Fifteen batches of standard decoctions were clustered into two types,and the medicinal materials produced from Jilin,Hebei,Shangdong could be used for the preparation of formula granules.CONCLUSION This reasonable and reliable method can provide references for the quality control and clinical application of Beidougen Formula Granules.

OBJECTIVETo study the clinical and pathologic features of gliosarcoma of cerebral hemispheres.

METHODSThe clinicopathologic features of 10 cases of gliosarcoma involving cerebral hemispheres were reviewed. Immunohistochemical study was carried out using EnVision method.

RESULTSThe mean age of the patients was 54 years and the male-to-female ratio was 6 to 4. Clinical symptoms included headache (6/10), nausea/vomiting (5/10), and sensory or motor impairment (4/10). Nine of the cases were primary gliosarcoma, with maximum diameter ranging from 2.4 to 5.5 cm (mean = 4.2 cm). The remaining case represented secondary gliosarcoma involving skull base and extracranial tissues. Histologic examination showed a biphasic pattern in all cases. Regarding the glial component, there were 9 cases of pleomorphic glioblastoma and 1 case of giant cell glioblastoma. Reticulin stain was positive in all cases. Immunohistochemical study showed that the tumor cells variably expressed GFAP (10/10), p16 (4/10), EGFR (1/10), CD68 (1/10) and p53 (6/10). The Ki-67 index ranged from 15% to 70% (mean = 34%). Six patients had follow-up data available. One patient was disease-free for 45 months and 5 patients died of the disease at 3 to 17 months after the operation (mean duration of survival = 9 months).

CONCLUSIONSGliosarcoma is a highly aggressive tumor, often locates in the deeper part cerebral hemispheres and has a relatively short duration of symptoms. It carries a poor prognosis. GFAP immunostain and reticulin stain are helpful in confirming the diagnosis. p53 and p16 are also expressed in some cases.

Adult ; Brain Neoplasms ; metabolism ; pathology ; Cerebrum ; pathology ; Female ; Glioblastoma ; metabolism ; pathology ; Gliosarcoma ; metabolism ; pathology ; Humans ; Male ; Middle Aged ; Neuroglia ; pathology

For the past few years, viral diseases such as Coronavirus Disease 2019, Influenza, and Ebola hemorrhagic fever have become more severe and more frequent. For people’s health and the stable operation of the national economy, it is of increasing importance to research the pathogenesis of virus and host immune regulation mechanism, analyze the regulation of gene expression between virus and host, and surveil pathogenic viruses and prevent virus diseases. Transcriptome sequencing is a kind of technology at the RNA level that focuses on the expression characteristics of genes in a specific space-time state, and it is an indispensable tool for analyzing differential gene expression and researching differential splicing of mRNA. With the progress of molecular biology experimental technology and the maturity of bioinformatics analysis platforms, transcriptomics is developing towards the low-cost and low technical threshold, which is gradually transitioning from the research field to the clinical laboratory and changing the traditional cognition of clinical staff in viruses and viral diseases. It has been increasingly used in the research of viral transcription mechanisms, immune interaction between virus and host, tracking disease progression, and antiviral drug development. In order to provide a methodological reference for the research of virus mechanism and prevention and control of virus disease, here, we mainly review meta-transcriptome from three aspects: technical process, common software and application scenarios of virus and virus diseases, and briefly mention the method and applications of other transcriptomes, including a population of cells RNA sequencing (Bulk RNA-seq), Single-cell RNA sequencing (ScRNA-seq), Single-nuclear RNA sequencing (SnRNA-seq), and Spatial Transcriptome (ST).

AIM To investigate the consistency of chemical constituents between formula granules and standard decoction of Coptidis Rhizoma.METHODS Eighteen batches of standard decoctions were prepared,after which the extraction rate and contents,transfer rates of magnolflorine,jatrorrhizine,columbamine,epiberberine,coptisine,palmatine,berberin were determined,HPLC characteristic chromatograms were established.RESULTS There were 11 common peaks in the characteristic chromatograms of 18 batches of standard decoctions and 24 batches of formula granules with the similarities of 0.861-1.000,which were clusterd into two categories.The formula granules and standard decoction demonstrated approximated extraction rate and contents,transfer rates of index constituents.CONCLUSION The chemical constituents between formula granules and standard decoction of Coptidis Rhizoma display good consistency,which can provide references for the quality control,process research and clinical application of the former.

OBJECTIVE: To detect the levels of Dickkopf-1 (DKK-1) in the plasma of patients with rheumatoid arthritis (RA), and to analyze their correlation with peripheral blood T cell subsets and clinical indicators. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to detect plasma DKK-1 levels in 32 RA patients and 20 healthy controls, and to record the various clinical manifestations and laboratory indicators of the RA patients, and flow cytometry to detect peripheral blood T cell subsets in the RA patients (Including Treg, nTreg, aTreg, sTreg, Teff, Tfh, CD4⁺CD161⁺T, CD8⁺T, CD8⁺CD161⁺T cells). The plasma DKK-1 levels between the two groups were ompared, and its correlation with peripheral blood T cell subsets and clinical indicators analyzed. RESULTS: (1) The plasma DKK-1 concentration of the RA patients was (124.97±64.98) ng/L. The plasma DKK-1 concentration of the healthy control group was (84.95±13.74) ng/L. The plasma DKK-1 level of the RA patients was significantly higher than that of the healthy control group (P < 0.05), and the percentage of CD8⁺CD161⁺T cells in the peripheral blood of the RA patients was significantly higher than that of the healthy control group (P < 0.05). (2) The plasma DKK-1 level was positively correlated with erythrocyte sedimentation rate (r=0.406, P=0.021), DAS28 score (r=0.372, P=0.036), immunoglobulin G(r=0.362, P=0.042), immunoglobulin A(r=0.377, P=0.033); it had no correlation with age, course of disease, C-reactive protein, rheumatoid factor, anti-cyclic citrullinated peptide antibody, immunoglobulin M, complement C3, complement C4, white blood cell, neutrophil ratio. (3) The plasma DKK-1 level in the RA patients was positively correlated with the percentage of peripheral blood CD161⁺CD8⁺T cells (r=0.413, P=0.019);it had no correlation with Treg, nTreg, aTreg, sTreg, Teff, Tfh, CD4⁺CD161⁺T, CD8⁺T cells. (4) The percentage of CD161⁺CD8⁺T cells was negatively correlated with erythrocyte sedimentation rate (r=-0.415, P=0.004), C-reactive protein (r=-0.393, P=0.007), DAS28 score(r=-0.392, P=0.007), rheumatoid factor (r=-0.535, P < 0.001), anti-citrullinated protein antibody (r=-0.589, P < 0.001), immunoglobulin G(r=-0.368, P=0.012) immunoglobulin M (r=-0.311, P=0.035); it had no correlation with age, disease course, immunoglobulin A, complement C3, complement C4, white blood cell, and neutrophil ratio. CONCLUSION RA patients' plasma DKK-1 levels and the percentage of CD8⁺CD161⁺T cells in T cell subsets in peripheral blood increase, which may be related to the secretion of proinflammatory cytokines in patients; DKK-1 is involved in the regulation of bone homeostasis and can be used as a marker of bone destruction in RA.
Arthritis, Rheumatoid ; Blood Sedimentation ; Humans ; Intercellular Signaling Peptides and Proteins/blood* ; Plasma ; Rheumatoid Factor ; T-Lymphocyte Subsets

Objective To explore the semi-supervised learning (SSL) algorithm for long-tail endoscopic image classification with limited annotations. Method We explored semi-supervised long-tail endoscopic image classification in HyperKvasir, the largest gastrointestinal public dataset with 23 diverse classes. Semi-supervised learning algorithm FixMatch was applied based on consistency regularization and pseudo-labeling. After splitting the training dataset and the test dataset at a ratio of 4:1, we sampled 20%, 50%, and 100% labeled training data to test the classification with limited annotations. Results The classification performance was evaluated by micro-average and macro-average evaluation metrics, with the Mathews correlation coefficient (MCC) as the overall evaluation. SSL algorithm improved the classification performance, with MCC increasing from 0.8761 to 0.8850, from 0.8983 to 0.8994, and from 0.9075 to 0.9095 with 20%, 50%, and 100% ratio of labeled training data, respectively. With a 20% ratio of labeled training data, SSL improved both the micro-average and macro-average classification performance; while for the ratio of 50% and 100%, SSL improved the micro-average performance but hurt macro-average performance. Through analyzing the confusion matrix and labeling bias in each class, we found that the pseudo-based SSL algorithm exacerbated the classifier's preference for the head class, resulting in improved performance in the head class and degenerated performance in the tail class. Conclusion SSL can improve the classification performance for semi-supervised long-tail endoscopic image classification, especially when the labeled data is extremely limited, which may benefit the building of assisted diagnosis systems for low-volume hospitals. However, the pseudo-labeling strategy may amplify the effect of class imbalance, which hurts the classification performance for the tail class.
Supervised Machine Learning ; Algorithms

BACKGROUNDA multi-center large scale study is needed to confirm the efficacy and safety of domestic peritoneal dialysis (PD) solutions. Some researchers believe that 6 L/d is enough for adequate dialysis, but there is no multi-center prospective study on Chinese population to confirm this. In this study, we evaluated the efficacy and safety of domestic PD solution (Changfu) and its difference between 6 L and 8 L dosage.

METHODSAdult PD patients who had taken PD therapy for at least one month were selected and divided into four groups according to two dialysis solution brands and two dialysis dosages, i.e., 6 L dose with Changfu dialysis solution, 6 L dose with Baxter dialysis solution, 8 L dose with Changfu dialysis solution, and 8 L dose with Baxter dialysis solution. After 48 weeks, the changes of primary and secondary efficacy indices were compared between different types and different dosages. We also analyzed the changes of safety indices.

RESULTSChanges of Kt/V from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of creatinine clearance rate (Ccr). Normalized protein catabolic rate (nPCR) from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of net ultrafiltration volume (nUF) and estimated glomerular filtration rate (eGFR). Changes of nPCR from baseline to 48 weeks between 6 L and 8 L showed no statistical differences; so did those of nUF and eGFR. The decline of Kt/V from baseline to 48 weeks in 6 L group was more than that in 8 L group. Change of Ccr was similar. During the 48-week period, the mean Kt/V was above 1.7/w, and mean Ccr was above 50 L×1.73 m(-2)×w(-1). More adverse events were found in Changfu group before Changfu Corporation commenced technology optimization, and the statistical differences disappeared after that.

CONCLUSIONSThe domestic PD solution (Changfu) was proven to be as effective as Baxter dialysis solution. During 48-week period, a dosage of 6 L/d was enough for these patients to reach adequate PD. Clinical study promotes technological optimization, further helps to improve the safety indices of the medical products.

Adolescent ; Adult ; Aged ; Dialysis Solutions ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Peritoneal Dialysis ; methods ; Young Adult