Metastasis accounts for 90% of breast cancer deaths, where the lethality could be attributed to the poor drug accumulation at the metastatic loci. The tolerance to chemotherapy induced by breast cancer stem cells (BCSCs) and their particular redox microenvironment further aggravate the therapeutic dilemma. To be specific, therapy-resistant BCSCs can differentiate into heterogeneous tumor cells constantly, and simultaneously dynamic maintenance of redox homeostasis promote tumor cells to retro-differentiate into stem-like state in response to cytotoxic chemotherapy. Herein, we develop a specifically-designed biomimic platform employing neutrophil membrane as shell to inherit a neutrophil-like tumor-targeting capability, and anchored chemotherapeutic and BCSCs-differentiating reagents with nitroimidazole (NI) to yield two hypoxia-responsive prodrugs, which could be encapsulated into a polymeric nitroimidazole core. The platform can actively target the lung metastasis sites of triple negative breast cancer (TNBC), and release the escorted drugs upon being triggered by the hypoxia microenvironment. During the responsiveness, the differentiating agent could promote transferring BCSCs into non-BCSCs, and simultaneously the nitroimidazole moieties conjugated on the polymer and prodrugs could modulate the tumor microenvironment by depleting nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and amplifying intracellular oxidative stress to prevent tumor cells retro-differentiation into BCSCs. In combination, the BCSCs differentiation and tumor microenvironment modulation synergistically could enhance the chemotherapeutic cytotoxicity, and remarkably suppress tumor growth and lung metastasis. Hopefully, this work can provide a new insight in to comprehensively treat TNBC and lung metastasis using a versatile platform.

Due to the rapid proliferation and growth of tumor cells, hypoxic microenvironment exists in many solid tumors, and hypoxia inducible factors (HIF) are critical for sensing oxygen tension within tumors and subsequently mediating the activation of hypoxia responses. Hepatocellular carcinoma (HCC) is one of the most hypoxic tumors. This article summarizes the mechanism of action of HIF in promoting the development and progression of HCC by promoting glycolysis, angiogenesis, invasion and metastasis, immune escape, and cancer stem cell formation. At present, the development of targeted drugs for HIF inhibitors has broad prospects in the treatment of HCC, and the detection of HIF also has a potential value in prognostic evaluation HCC.

Rabdosia serra(R.serra),an important component of Chinese herbal tea,has traditionally been used to treat hepatitis,jaundice,cholecystitis,and colitis.However,the chemical composition of R.serra and its effect against colitis remain unclear.In this study,the chemical composition of the water extract of R.serra was analyzed using ultra performance liquid chromatography coupled with a hybrid linear ion trap quadrupole-orbitrap mass spectrometer(UPLC-LTQ-Orbitrap-MS).A total of 46 compounds,comprising ent-kaurane diterpenoids,flavonoids,phenolic acids,and steroids,were identified in the water extract of R.serra,and the extract could significantly alleviate dextran sulfate sodium salt-induced colitis by improving colon length,upregulating anti-inflammatory factors,downregulating proinflammatory fac-tors,and restoring the balance of T helper 17/T regulatory cells.R.serra also preserved intestinal barrier function by increasing the level of tight junction proteins(zonula occludens 1 and occludin)in mouse colonic tissue.In addition,R.serra modulated the gut microbiota composition by increasing bacterial richness and diversity,increasing the abundance of beneficial bacteria(Muribaculaceae,Bacteroides,Lactobacillus,and Prevotellaceae_UCG-O01),and decreasing the abundance of pathogenic bacteria(Turi-cibacter,Eubacterium_fissicatena_group,and Eubacterium_xylanophilum_group).Gut microbiota depletion by antibiotics further confirmed that R.serra alleviated colitis in a microbiota-dependent manner.Overall,our findings provide chemical and biological evidence for the potential application of R.serra in the management of colitis.

In recent years, Internet plus medical care has developed rapidly, and many aspects including quality control need to be further standardized. The authors summarized the current situation of quality control in Internet plus medical care, analyzed the difficulties of quality control in Internet plus medical care, and constructed the quality control system and evaluation focus of the Internet plus medical care system from the following aspects: management system framework, personnel management, quality control in the process, post evaluation and continuous improvement.

Objective To establish the target measurement uncertainty(MU)of the routine coagulation assay according to the External Quality Assessment data(EQA)of routine coagulation assay. Methods Beijing Center for Clinical Laboratory(BCCL)established the target measurementuncertainty for routine coagulation assayswith the"up-down"methodon the basis of 93 clinical laboratoriesEQA datain BeijingThese assays includedActivated partial thromboplastine time(APTT), Fibrinogen(FBG), International Normalized Ratio(INR), Prothrombin time(PT), Thrombin time(TT)and D-dimer, Compared with CLIA′88,the proficiency of current coagulation assayswas observed.Results The MU of six routine coagulation assayscompared with CLIA ′88 showed that: The 90th percentile MU met the creteriain APTTof group B,FBG of group A&B&C,INR of group B and D-dimer of group B.The 75th percentile MU met the creteriainINR of group A&C,PT of group C.The medium met the creteriainAPTT of group A&C,PT of group A and INR of group D.Conclusions Target Measurement Uncertainty was establishedin routine coagulation assay by using EQA data only,whichcan simplify the procedure of determining MU and continuously update MU according to the frequency of EQA.It has good clinical practical value.However, the applicability of this method should also be considered.

Objective: To investigate the clinical and immunological laboratory features, mutations in SH2D1A gene and SAP protein expression in four children of two families with X-linked lymphoproliferative disease type 1(XLP-1). Method: Four patients (Family A including Patient 1 and Patient 2, Family B including Patient 3 and Patient 4) and their maternal relatives were enrolled in this study. The clinical manifestation, EBV infection status and chest CT scan were analyzed. The absolute and relative numbers of lymphocyte subsets, T lymphocyte proliferative response, SAP protein expression were assessed by flow cytometry. Quantification of signal joint TCR rearrangementexcision circle (sjTRECs), CDR3 spectratyping of TCRvβ and gene mutation of SH2D1A were detected by PCR based on genomic DNA or cDNA. Result: Four male patients from two families were diagnosed with XLP-1. The ages of disease onset were more than 1 year, more than 1 year, more than 1 month and 6 months. The ages at diagnosis were nine years and ten months, sixteen years and eight months, fourteen years and ten months, four years and nine months. All patients had recurrent infections and EBV infection. Patients 1, 2, and 3 had agammaglobulinemia and Patient 4 had hypogammaglobulinemia. Chest CT scan showed all patients had atelectasis and pneumonia, and Patient 3 had bronchiectasis. Patient 3 was diagnosised as Burkitt lymphoma. For immunological function, all patients exhibited reduced CD4/CD8 ratios, increased numbers of exhausted T lymphocyte, decreased number of NK cell. The numbers of total B lymphocyte and naïve B lymphocyte were normal, but the number of memory B lymphocyte declined in all cases. Four patients′ copy numbers of sjTRECs were low and CDR3 spectratypings of TCRvβ showed mildly skewed. But their T lymphocyte proliferative response was normal. SAP protein expression in four cases were measured by flow cytometry. Two patients from Family A were absent and two patients from Family B showed decreased values. SH2D1A gene sequence analysis showed that the patients of Family A harbored a nonsense mutation (c.163 C>T; p.R55X) in exon 2. Their mother and two sisters were carriers. A missense mutation of SH2D1A gene (c.278 G>A; p.G93D) in exon 3 was found in the patients of Family B. The mother was carrier. Four patients remain survived, Patient 3 gave up treatment, other three patients received IVIG therapy. Conclusion Four patients with XLP-1 from two families characterized by agammaglobulinemia have an extreme vulnerability to Epstein-Barr virus (EBV) infection. The functions of T cell, B cell and NK cell are impaired at different stages. The detection of SAP protein and SH2D1A gene are the key methods for diagnosis of XLP-1.

Objective To investigate the internal quality control ( IQC ) on clinical chemistry , clinical immunology and clinical hematology in mutual recognition laboratories in medical institutions in Beijing.Methods By means of questionnaire survey and on -site investigation, fresh frozen serum and whole blood samples with assigned values by reference method were measured to investigate the status of IQC on clinical chemistry , clinical immunology and clinical hematology in 142 mutual recognition laboratories in medical institutions of Beijing,and results were analyzed.Results 142 copies of questionnaireson clinical chemistry, clinical immunology and clinical hematology were send out and 120, 97, and 101 laboratories returned the questionnaires respectively .The information feedback rate was 84.5%, 68.3% and 71.1%respectively .All the questionnaires were effective .Questionnaires survey results showed that more than 50%laboratories set up quality control goals and the most of the goals were probability for error detection ( Ped) 95%, probability for false rejection(Pfr)5%;About 70% laboratories usecd the same quality control plan for different tests ;The most frequently used quality control rules are 12s/13s/22s.On-site investigation showed that ,take the results of clinical chemistry for example , based on the desirable biological variation and WS/T 403 -2012 , most of the tests can't meet the quality control goalsunder the existing quality controlcondition.Conclusion Clinical laboratories should consider their actual situations , assess their own qualitylevels that they can reach , set reasonable quality standards for themselves , and make appropriateindividualized quality control plan.

OBJECTIVE:To perfect public participation system of food and drug safety in China and establish“society multi-governance”of food and drug safety. METHODS:The problems of public participation in food and drug safety administration were analyzed in China. Referring to the experience of USA,Japan,South Korea and other developed countries in stage of food and drug safety legislative decision-making,regulation and enforcement and dispute settlement,the countermeasures were put forward to perfect public participation system of food and drug safety. RESULTS & CONCLUSIONS:The public is in a passive position and shows weak right of speech in legislative decision-making stage;the public is not active and shows weak awareness of partici-pating in management in regulation and enforcement stage;public interest litigation system in dispute settlement stage has not been established. Those problems impede the generation of“society multi-governance”of food and drug safety in China. In United States,Japan,South Korea and other developed countries,the position and right of the public participation can be guaranteed com-pletely through establishing complete legal system,strengthening government information transparency,improving complaints sys-tem and public interest litigation system,etc. Our country can perfect the system of public participation in the food and drug safety and promote the generation of“society multi-governance”of food and drug safety by detailing the regulations in legislative deci-sion-making,emphasizing the information opening and feedback,strengthening the propaganda of public responsibility conscious-ness,setting up scientific food and drug safety complaint and reparting system and establishing public interest litigation system.

OBJECTIVETo explore the effect of vitamin A (VA) combined iron supplements on iron metabolic homeostasis for preschoolers.

METHODSAbout 445 preschoolers with aged 3-6 years old from eight kindergartens in Pixian county, Chengdu were recruited into this trial from March to September, 2011. All subjects met the inclusion criteria were randomly divided into four groups using random number table: sole VA supplementation group (VA group, a single oral dose of VA at about 200 000 units), sole iron supplementation group (FE group, daily oral supplementation with the element iron 1-2 mg·kg(-1)·d(-1) for five days a week, lasting for 6 months), the combined supplementation of VA and iron group (VF group) and control group (CO group, no VA and iron supplementation). The concentration of serum VA, serum ferritin (SF), serum transferring receptor (sTfR), C-reactive protein (CRP) and hemoglobin (Hb) were measured from 3 ml vein blood. The sTfR-SF index (TFR-F index) and total body iron content (TBIC) before and after intervention were calculated. The differences of these indexes between groups before and after intervention were analyzed.

RESULTSThe level of sTfR before intervention in VA group ((1.78 ± 0.17) mg/L) was significantly higher than that of after intervention ((1.18 ± 0.11)mg/L) (t = 28.88, P < 0.01). The levels of TFR-F index and TBIC in FE and VF groups before intervention ( (1.59 ± 0.37), (1.63 ± 0.40) and (9.04 ± 2.71), (9.26 ± 2.33) mg/kg, respectively) were all lower than those of after intervention (TFR-F index:(1.84 ± 0.51), (1.87 ± 0.45) and TBIC:(12.42 ± 3.49), (13.01 ± 2.98)mg/kg) (t values were 3.93, 3.78, 7.57 and 9.41, respectively, all P values were <0.01). The incidence of iron deficiency in VA, FE, and VF groups before intervention were 26% (25/95), 31% (30/98) and 31% (28/90) and were 41% (39/95), 10% (10/98) and 18% (16/90) for after intervention, respectively. The difference of this index in VA, FE and VF groups were significant (χ(2) values were 4.59, 12.50 and 4.31, respectively, all the P values were <0.05).

CONCLUSIONCombined VA and iron was as effective as VA alone or iron alone in decreasing the iron deficiency, the impact of VA intervention on iron metabolic homeostasis was mainly manifested in iron usage and mobilization, but showed no effect on total body iron content.

Anemia, Iron-Deficiency ; epidemiology ; Child ; Child, Preschool ; Dietary Supplements ; Female ; Homeostasis ; Humans ; Iron ; administration & dosage ; metabolism ; Male ; Nutritional Status ; Vitamin A ; administration & dosage ; pharmacology

This paper presents a removal method of electrogastrogram (EGG) baseline wander based on wavelet transformation. The basic idea of this method is using the low-frequency signal which is obtained through multi-scale decomposition of EGG signals to approximate the baseline wander of EGG, so the component of baseline wander is filtered out from the sampling EGG signals. The method was applied successfully to process the experimental data of dog EGG in our laboratory. The experimental data and analysis of results showed that this method could filter out the baseline wander of EGG, and this method would not affect the gastric spike and slow wave bandwidth signals, which could be shown from the characteristics of bandwidth filter of wavelet transformation.
Algorithms ; Animals ; Artifacts ; Dogs ; Electrodiagnosis ; Electrophysiological Phenomena ; Gastric Emptying ; physiology ; Gastrointestinal Motility ; physiology ; Myoelectric Complex, Migrating ; physiology ; Signal Processing, Computer-Assisted ; Wavelet Analysis