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

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

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

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

Objective: From a screening-focused perspective, to analyze the 30-year changes in disability adjusted life years (DALYs) caused by colorectal cancer (CRC) in China and in some other selected populations, to inform extent of burden of CRC and future related prevention and control in populations in China. Methods: Based on the data of Global Burden of Disease 2019 (GBD 2019), the DALYs, world standardized DALY rate, and the composition of different subgroups in China were collected. Joinpoint regression model was used to analyze the trend during 1990-2019, and comparison was made with the international data and population screening situation. The trend of DALY burden caused by CRC in China was predicted. Results: In 2019, the DALYs due to CRC in China was 6.395 million person-years, accounting for 26.3% of the global burden and 9.5% of all cancers burden in China; the DALYs in men accounted for 65.2%, in those aged ≥65 years old accounted for 44.8%, in the age group recommended by local screening guidelines (40-75 years) accounted for 73.7%. The years lived with disability accounted for 4.8%. Compared with 1990, the CRC-caused DALYs in China increased by 181.5% in 2019. Factors with the largest increase in the attributable percentage were high Body Mass Index (151.1%), diet high in red meat (86.4%) and diet high in processed meat (78.8%), etc. For DALY rate, it was 245.6/100 000 in 1990 and 320.6/100 000 in 2019, an increase of 30.5%. For reference, Australia (began in 2006), the UK (2006), and Japan (1992), where CRC population-wide screening has been conducted, had decreases in DALY rate of 36.0%, 28.6%, and 17.8%, respectively. The predication of DALYs suggested that without continued expansion of population-based screening, the DALYs in China would reach 7.7 million person-year-9.1 million person-year by 2030, an increase of 19.9%-41.8% compared with 2019. Conclusions: The burden of CRC-caused DALYs in China increased over the past 30 years, and would become more serious because of population aging and the concomitant disability problem. The age range recommended by the current local screening guideline could theoretically include 70% of the population from which the DALYs burden originates, however, the real-world population screening coverage is still limited. The observed decline in CRC-related DALY rate in selected countries was substantially due to the implementation of mass screening, indicating the importance of speedily expanding the population coverage of CRC screening in China.
Aged ; China/epidemiology* ; Colorectal Neoplasms/epidemiology* ; Cost of Illness ; Disability-Adjusted Life Years ; Early Detection of Cancer ; Humans ; Male ; Mass Screening ; Quality-Adjusted Life Years

UPLC-Q-TOF-MS combined with network pharmacology and experimental verification was used to explore the mechanism of acupoint sticking therapy(AST) in the intervention of bronchial asthma(BA). The chemical components of Sinapis Semen, Cory-dalis Rhizoma, Kansui Radix, Asari Radix et Rhizoma, and Zingiberis Rhizoma Recens were retrieved from TCMSP as self-built database. The active components in AST drugs were analyzed by UPLC-Q-TOF-MS, and the targets were screened out in TCMSP and Swiss-TargetPrediction. Targets of BA were collected from GeneCards, and the intersection of active components and targets was obtained by Venny 2.1.0. The potential targets were imported into STRING and DAVID for PPI, GO, and KEGG analyses. The asthma model induced by house dust mite(HDM) was established in mice. The mechanism of AST on asthmatic mice was explored by pulmonary function, Western blot, and flow cytometry. The results indicated that 54 active components were obtained by UPLC-Q-TOF-MS and 162 potential targets were obtained from the intersection. The first 53 targets were selected as key targets. PPI, GO, and KEGG analyses showed that AST presumedly acted on SRC, PIK3 CA, and other targets through active components such as sinoacutine, sinapic acid, dihydrocapsaicin, and 6-gingerol and regulated PI3 K-AKT, ErbB, chemokine, sphingolipid, and other signaling pathways to intervene in the pathological mechanism of BA. AST can improve lung function, down-regulate the expression of PI3 K and p-AKT proteins in lung tissues, enhance the expression of PETN protein, and reduce the level of type Ⅱ innate immune cells(ILC2 s) in lung tissues of asthmatic mice. In conclusion, AST may inhibit ILC2 s by down-regulating the PI3 K-AKT pathway to relieve asthmatic airway inflammation and reduce airway hyperresponsiveness.
Acupuncture Points ; Animals ; Asthma/drug therapy* ; Drugs, Chinese Herbal ; Immunity, Innate ; Lymphocytes ; Mice ; Network Pharmacology