[Overview and prospects of an in vitro cell model for studying liver fibrosis].

Liver fibrosis incidence and adverse outcomes are high; however, there are no known chemical drugs or biological agents that are specific and effective for treatment. The paucity of a robust and realistic in vitro model for liver fibrosis is one of the major causes hindering anti-liver fibrosis drug development. This article summarizes the latest progress in the development of in vitro cell models for liver fibrosis, with a focus based on the analysis of induction and activation of hepatic stellate cells, cell co-culture, and 3D model co-construction, as well as concurrent potential methods based on hepatic sinusoidal endothelial cell establishment.

[Association of DNA methylation of IFNG gene with no/low response to hepatitis B vaccine in children].

Objective: To explore the association of DNA methylation with immune response to hepatitis B (HepB) vaccine in Han nationality children from Guangxi province. Methods: A total of 263 children aged 8-9 months who had completed HepB immunization program were recruited from three hospitals in Guangxi province by using unmatched case-control method. Children with the HepB surface antibody concentration(Anti-HBs)<100 mIU/ml was set as the case group and ≥100 mIU/ml as the control group. Multiplex PCR and heavy sulfite sequencing were used to treat the samples. Illumina platform was used for high-throughput DNA methylation sequencing of IFNG gene target regions and CpG sites. Unconditional logistic regression was used to analyze the association between cytosine-phospho-guanosine DNA methylation at 18 loci of IFNG gene and HepB immune response level. Results: There were 104 children in the case group and 159 in the control group. The median (Q1, Q3) level of anti-HBs in two groups were 62.34 (30.06, 98.88) mIU/ml and 1 089.10 (710.35, 1 233.45) mIU/ml. The methylation levels of IFNG_1 gene 44 and 93 locus in the case group were higher than those in the control group (P<0.05). The unconditional logistic regression model showed that the DNA methylation level of IFNG_1 gene at 44 (OR=1.18, 95%CI: 1.03-1.35) and 93 (OR=1.21, 95%CI: 1.07-1.38) locus was associated with the HepB response level. Conclusion: The changes of DNA methylation at locus 44 and 93 of IFNG_1 gene may be relevant factors affecting the response level of HepB in Han nationality children from Guangxi province.

Effects of varying dietary intoxication with lead on the performance and ovaries of laying hens.

In this study, we explored the effect of dietary lead nitrate on zootechnical performance, egg quality, accumulation of ovarian plumbum (Pb), follicular atresia rate, and ovarian oxidative stress in laying hens. Furthermore, the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling molecule was studied to reveal the molecular mechanism of the stress. A total of 512 Hy-Line Brown laying hens aged 40 wk were randomly allocated to 4 groups (with 8 pens per group and 16 hens per pen). The Pb concentrations used to treat the 4 groups were 3.20, 33.20, 63.20, and 93.20 mg/kg. The results revealed that dietary Pb exposure significantly linearly reduced the zootechnical performance (P < 0.01) but significantly linearly increased the feed conversion ratio (P < 0.01). The dietary Pb exposure significantly linearly reduced the Haugh units (P < 0.01), albumen height (P < 0.01), eggshell thickness (P < 0.01), and eggshell strength (P < 0.01). In addition, the dietary Pb exposure significantly enhanced the follicular atresia rate (P < 0.01). After dietary Pb exposure, superoxide dismutase (P < 0.01) and glutathione peroxidase (GSH-Px) (P < 0.01) activities and glutathione (P < 0.01) contents were significant decreased quadratically, and there were significant linear decreases in the activities of catalase (CAT) (P < 0.01) and glutathione reductase (GR) (P < 0.01), whereas malondialdehyde content was significantly linearly increased (P < 0.01). In addition, except for manganese superoxide dismutase, the gene expressions of copper-zinc superoxide dismutase (P < 0.01), CAT (P < 0.01), and GR (P < 0.01) were significant decreased linearly. In addition, there were significantly quadratic decreases in the mRNA expressions of GSH-Px (P < 0.01) and Nrf2 (P < 0.01). By way of contrast, the Kelch-like ECH-associated protein 1 (Keap1) gene expression was significantly linearly increased (P < 0.01). In conclusion, dietary Pb exposure could induce oxidative stress by impairing the Nrf2-Keap1 signal pathway in the ovaries of laying hens.

[The 476th case: skin rash, edema, thrombocytopenia and anemia].

The 21-year-old male patient was admitted to the Department of Rheumatology and Immunology at Peking Union Medical College Hospital with chief complaints of "skin rash for 1 year and edema for 2 months". He was diagnosed with systemic lupus erythematosus (SLE) with renal, cardiac and hematological involvement. Remission was not achieved after glucocorticoid pulse treatment. The patient experienced oliguria, malignant hypertension, accompanied by thrombocytopenia and low serum complements, and elevated lactate dehydrogenase and serum creatinine. Schistocytes were seen in the peripheral blood smear. Thrombotic microangiopathy (TMA) secondary to SLE was diagnosed. Though plasma exchange was partially effective, TMA could not be controlled yet. The activity of serum von Willebrand factor -cleaving protease (ADAMTS 13) was 100%, and ADAMTS 13 inhibitor was negative. Finally, remission of the disease was achieved after second glucocorticoid pulse therapy and rituximab treatment. At the 3-month follow-up, the patient's condition was stable with mild anemia and normal platelet count. Patients with TMA secondary to SLE are heterogenous, while normal ADAMT 13 activity indicates poor prognosis. Early and aggressive treatment is important for disease control, and plasma exchange is helpful as a supportive care.

Cost-effectiveness analysis of capecitabine plus bevacizumab versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer from Chinese societal perspective.

PURPOSE: The aim of the study was to evaluate the cost-effectiveness of capecitabine plus bevacizumab compared with capecitabine alone in elderly patients with metastatic colorectal cancer (CRC) from a Chinese societal perspective. METHODS: A decision-analytic Markov model was conducted to simulate the process of metastatic CRC. Three distinct health states: progression-free survival (PFS), progressive disease and death were included. Clinical data were derived from the AVEX trial. Health effectiveness was denoted in quality-adjusted life years (QALYs) and health utilities were derived from previously published studies. Incremental cost-effectiveness ratio (ICER) was regarded as the primary endpoint and willingness-to-pay (WTP) threshold was set at $26,753.37/QALY (3 × per capita GDP of China, 2017). One-way sensitivity analyses and probabilistic sensitivity analysis were also performed to explore the parameters uncertainty in the study. RESULTS: Over a 10-year life horizon, capecitabine plus bevacizumab gained 1.14 QALYs at an average cost of $21,609.48, while the effectiveness and cost of capecitabine group were 0.99 QALYs and $7274.83, respectively. The ICER between the two groups was $95,564.33/QALY. Parameters that mostly influenced the results of the model were utility of PFS state, duration of PFS state for capecitabine plus bevacizumab, total cost of PFS state for capecitabine plus bevacizumab and price of bevacizumab. The probabilities of capecitabine plus bevacizumab and capecitabine as the dominant option were 0% and 100% at the WTP threshold of $26,753.37/QALY. CONCLUSIONS: The results of the study showed that capecitabine plus bevacizumab is unlikely to be a cost-effective treatment option for elderly patients with metastatic CRC.

Effects of SIRT1/Akt pathway on chronic inflammatory response and lung function in patients with asthma.

OBJECTIVE: Asthma is the most common chronic airway inflammatory disease. Sirtuin 1 (SIRT1) exerts a crucial effect on regulating chronic inflammatory responses. Therefore, this study aims to explore the effect of SIRT1 on the pathogenesis of asthma. MATERIALS AND METHODS: Serum level of SIRT1 in asthma patients and healthy controls was detected by Western blot. Correlation between SIRT1 level and pulmonary function in asthma patients was analyzed. Subsequently, asthma model in mouse was established. Primary airway epithelial cells were extracted from asthma mice and control mice to detect SIRT1 level. Furthermore, relative levels of Akt and interleukin 6 (IL-6) were detected in 16HBE cells. Regulatory effects of Akt on SIRT1 in 16HBE cells were determined as well. RESULTS: SIRT1 was highly expressed in serum of asthma patients, which was negatively correlated with FEV1/FVC (r=-0.27, **p<0.01). Both mRNA and protein levels of SIRT1 were downregulated in primary airway epithelial cells extracted from asthma mice compared with those from controls. SIRT1 knockdown in 16HBE cells upregulated IL-6 expression, which was reversed by Akt inhibitors. CONCLUSIONS: SIRT1 regulates IL-6 level via Akt pathway, thereafter affecting pulmonary function in asthma patients.

[The 469th case: multiple cutaneous abscesses, pelvic mass, and lung cavities].

A 28-year-old woman with multiple abscesses for 2 month and fever for 1 month was admitted in Peking Union Medical College Hospital. The skin abscesses gradually developed at skull, face, abdominal wall and pelvis. Laboratory examinations related to inflammatory reactions were strongly high including erythrocyte sedimentation rate 99 mm/1 h,C-reactive protein160.28 mg/L and ferritin 1 584 µg/L. Multiple nodules and cavities were detected in lungs. And vesico-cervical fistula was found during exploratory laparotomy. The pathological tests of abdominal tissues demonstrated necrosis and granuloma. Evidence of infectious diseases was not definite. Positive anti-proteinase 3 (PR3) antibody confirmed the diagnosis of granulomatosis with polyangiitis. After treated with glucocorticoid and immunosuppressants, the patient's symptoms improved remarkably. This case suggested that systemic vasculitis should be considered as a differential diagnosis of multiple abscesses which are not explained by infections.

High-transmission polarization-dependent active plasmonic color filters.

Plasmonic color filters, exhibiting great promise as an alternative for existing colorant-based filters, often only output one fixed color. Developing active color filters with controllable color output will lead to more compact color filter-based devices. In this paper, we present an approach to achieve active color filtering with a polarization-dependent plasmonic structural color filter, which comprises arrays of asymmetric cross-shaped nanoapertures in an ultrathin film of silver. A systematical study for aperture size, array period, and the thickness of silver film dependences of color filter properties is carried out, and strategies for polarization-dependent color filter designing are generated. A polarization-dependent and high tunability of color can be achieved by selecting the appropriate nanostructure parameters, which imply many potential applications.

Glutamine alleviates heat stress-induced impairment of intestinal morphology, intestinal inflammatory response, and barrier integrity in broilers.

The aim of this study was to investigate the protective effect of glutamine (Gln) on the intestinal morphology, intestinal inflammatory response, and barrier integrity in broilers exposed to high ambient temperature. Three-hundred-sixty 21-d-old Arbor Acres broilers (half male and half female) were randomly allocated to 4 treatment groups in a completely randomized design, each of which included 6 replicates with 15 birds per replicate, for 21 d. The 4 treatment groups were as follows: the control group, in which birds were kept in a thermoneutral room at 22 ± 1°C (no stress, NS; fed a basal diet); the heat stress group (36 ± 1°C for 10 h/d from 08:00 to 18:00 h and 22 ± 1°C for the remaining time, heat stress (HT); fed a basal diet); and heat stress + Gln group (0.5 and 1.0% Gln, respectively). Compared to the NS group, broilers in the HT group had lower villus height (P < 0.05), higher crypt depth (P < 0.05), higher D-lactic acid and diamine oxidase (DAO) activity (P < 0.05), higher soluble intercellular adhesion molecule-1 (sICAM-1) concentration (P < 0.05), higher tumor necrosis factor (TNF)-α/interleukin (IL)-10 (P < 0.05), and lower tight junction protein expression levels (P < 0.05). Compared with birds in the HT, birds in the HT + Gln group exhibited increased villus height (P < 0.05), decreased D-lactate and DAO activity (P < 0.05), decreased sICAM-1 concentration (P < 0.05), and mediate the secretion of cytokines (P < 0.05), as well as increased zonula occludens-1 (ZO-1), claudin-1, and occludin mRNA expression levels (P < 0.05). In conclusion, these results indicate that supplementation with Gln was effective in partially ameliorating the adverse effects of heat stress on intestinal barrier function in broilers by promoting epithelial cell proliferation and renewal, modifying the function of the intestinal mucosa barrier, and regulating the secretion of cytokines.

[The 461th case: fever, hematuria, and right lumbar pain].

A 56-year-old female was admitted to the Department of Rheumatology, Peking Union Medical College Hospital with complaint of recurrent fever and acute lumbar pain. Fever was complicated with malaise, cough and occasional blood-streaked sputum. Lab tests showed elevated white blood cell count, increased serum creatinine, erythrocyte sedimentation rate and C-reactive protein. Other lab findings included severe anemia, hematuria, and proteinuria. Immunological examinations were positive for antinuclear antibodies, antineutrophil cytoplasmic antibodies and antiglomerular basement membrane antibody. Ultrasonography and CT scan detected a huge spontaneous perirenal hematoma at right side. Angiography revealed multiple microaneurysms on bilateral renal arteries and branches. A diagnosis of systemic vasculitis was suggested. Under the combination therapy of corticosteroids and cyclophosphamide, the patient presented sustained remission for one year. This case indicates that prompt and sufficient treatment of primary disease is essential to a promising outcome.

Identification of glutathione S-transferases in Bemisia tabaci (Hemiptera: Aleyrodidae) and evidence that GSTd7 helps explain the difference in insecticide susceptibility between B. tabaci Middle East-Minor Asia 1 and Mediterranean.

The Bemisia tabaci (Gennadius) (Hemiptera:Aleyrodidae) species complex includes invasive and destructive pests of field crops, and the sibling species MEAM1 and MED are its two most damaging members. Previous research indicated that the replacement of Middle East-Minor Asia 1 (MEAM1) by Mediterranean (MED) as the dominant B. tabaci species in China can be mainly attributed to MED's greater tolerance to insecticides. Glutathione S-transferases (GSTs) play important roles in the detoxification of hydrophobic toxic compounds. To increase our understanding of differences in insecticide resistance between B. tabaci MEAM1 and MED, we searched the genomic and transcriptomic databases and identified 23 putative GSTs in both B. tabaci MEAM1 and MED. Through measuring mRNA levels of 18 of the GSTs after B. tabaci MEAM1 and MED adults were exposed to the insecticide imidacloprid, we found that the expression levels were increased more in B. tabaci MED than in MEAM1 (in particular, the expression level of GST-d7 was increased by 4.39-fold relative to the control). Knockdown of GST-d7 in B. tabaci MED but not in B. tabaci MEAM1 resulted in a substantial increase in the mortality of imidacloprid-treated adults. These results indicate that differences in GST-d7 may help explain why insecticide tolerance is greater in B. tabaci MED than in B. tabaci MEAM1.

[The 456th case: polyarthritis, dry cough, dyspnea on exertion].

A 53-year-old woman presented with arthralgia and dyspepsia on exertion.Symmetrical joint swelling and pain of bilateral hands with pigmentation sedimentation in the articular surfaces, dry cough and short of breath were the main clinical manifestations.Elevated levels of erythrocyte sedimentation rate(89 mm/1 h), C-reactive protein (64.45 mg/L), IgG(31.22 g/L) and IgA (5.44 g/L). Rheumatoid factor was positive and anti-cyclic citrullinated peptide antibody was negative.Chest high-resolution computed tomography scan found that diffusely distributed lung nodules, round cysts with varying sizes and patchy ground glass opacities.A significant plasma cell infiltration and amyloid deposition were seen in lung tissue.The patient was finally diagnosed as rheumatoid arthritis, interstitial lung disease and pulmonary nodules.Combination therapy of prednisone 7.5 mg qodpo, thalidomide 50 mg qdpo, tocilizumab 560 mg iv once per month for 1 month.Chest computed tomography showed stable lung nodules, however, pulmonary interstitial lesions gradually aggravated.

[The 455th case: swollen leg, jaundice and mental disturbance].

A 17-year-old young man with a history of swollen leg and intermittent jaundice was presented to Peking Union Medical College Hospital with acute fever and mental disturbance. He developed deep venous thrombosis, acute myocardial infarction and plantar skin necrosis during the past four years, and was presented with an acute episode of fever, thrombocytopenia, acute kidney injury, acute myocardial infarction, mental disturbance, and obstructive jaundice. Laboratory tests showed schistocytes on peripheral blood smear.High titer of antiphospholipid antibodies was detected.Strikingly, the activity of a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS13)was significantly decreased without the production of inhibitors. Images indicated stenosis of the common bile duct, common hepatic duct, and cystic duct, which caused dilation of bile ducts and the gall bladder. Corticosteroids and anticoagulation therapy were effective at first, but the disease relapsedonce the corticosteroids tapered down. Plasma exchange was administrated for 17 times, which was effective temporarily during this episode. Methylprednisolone pulse therapy, intravenous immunoglobulin, rituximab, anticoagulation therapy, and bile drainage, were all tried but still could not control the disease. The patient's family agreed to withdraw treatment after he developed septic shock.

Plasmonic reflection color filters with metallic random nanostructures.

We develop reflective color filters with randomly distributed nanodisks and nanoholes fabricated with hydrogen silsesquioxane and Ag films on silicon substrate. They exhibit high resolution, angle-independence and easily up-scalable fabrication, which are the most important factors for color filters for industrial applications. We uncover the underlying mechanism after systematically analyzing the localized surface plasmon polariton coupling in the electric-field distribution. The agreement of the experimental results with those from the simulation indicates that tunable colors across the visible spectrum can be obtained by simply varying the diameter of the nanodisks, promoting their applications.

Analysis of persistent changes to γ-aminobutyric acid receptor gene expression in Plutella xylostella subjected to sublethal amounts of spinosad.

A multi-generational approach was used to investigate the persistent effects of a sub-lethal dose of spinosad in Plutella xylostella. The susceptibility of various sub-populations of P. xylostella to spinosad and the effects of the insecticide on the gene expression of γ-aminobutyric acid receptor (GABAR) were determined. The results of a leaf dip bioassay showed that the sensitivity of P. xylostella to spinosad decreased across generations. The sub-strains had been previously selected based on a determined LC25 of spinosad. Considering that GABA-gated chloride channels are the primary targets of spinosad, the cDNA of P. xylostella was used to clone GABARα by using reverse transcription-polymerase chain reaction (RT-PCR). The mature peptide cDNA was 1477-bp long and contained a 1449-bp open reading frame encoding a protein of 483 amino acids. The resulting amino acid sequence was used to generate a neighbor-joining dendrogram, and homology search was conducted using NCBI BLAST. The protein had high similarity with the known GABAR sequence from P. xylostella. Subsequent semi-quantitative RT-PCR and real-time PCR analyses indicated that the GABAR transcript levels in the spinosad-resistant strain (RR, 145.82-fold) and in Sub1 strain (selected with LC25 spinosad for one generation) were the highest, followed by those in the spinosad-susceptible strain, the Sub10 strain (selected for ten generations), and the Sub5 strain (selected for five generations). This multi-generational study found significant correlations between spinosad susceptibility and GABAR gene expression, providing insights into the long-term effects of sub-lethal insecticide exposure and its potential to lead to the development of insecticide-resistant insect populations.

Effects of Oridonin on growth performance and oxidative stress in broilers challenged with lipopolysaccharide.

This study was conducted to investigate the effects of oridonin (ORI) on growth performance and antioxidant capacity in broiler chickens that were repeatedly challenged with lipopolysaccharide (LPS). A total of 384 one-day-old male Arbor Acre broiler chickens were randomly assigned to 8 treatments with 6 replicate cages per treatment and 8 birds per replicate. There were 4 dietary treatments: the control group (birds fed the basal diet), the ORI 50 group, the ORI 80 group, and the ORI 100 group (the basal diet supplemented with 50, 80, and 100 mg/kg oridonin, respectively). Broilers were intraperitoneally injected with either 250 µg/kg BW LPS or an equivalent amount of sterile saline at 16, 18, and 20 d of age. LPS decreased the average daily weight gain (ADG), the average daily feed intake (ADFI), and the feed conversion ratio (FCR) of broiler chickens (P < 0.05); oridonin supplementation had no effects on performance whether before or after LPS injection (P > 0.05). LPS stimulation increased the relative weight of the spleen and bursa (P < 0.05); oridonin inclusion markedly attenuated the increased spleen index (P < 0.05). Additionally, the LPS-induced increases in the concentrations of malondialdehyde (MDA) and decreases in activities of total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC) and catalase (CAT) were dramatically attenuated by oridonin in both the serum and liver (P < 0.05). Furthermore, LPS down-regulated the mRNA expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), copper and zinc superoxide dismutase (Cu/Zn-SOD), manganese superoxide dismutase (Mn-SOD), glutathione peroxidase (GPx1), and CAT in the liver (P < 0.05), However, oridonin inclusion increased the liver mRNA expression levels of Nrf2, Cu/Zn-SOD, Mn-SOD, CAT, and GPx1 (P < 0.05). It was concluded that the dietary oridonin supplementation at an optimum dose of 100 mg/kg improves the antioxidant capacity in broilers, as evidenced by the decrease in MDA and the increase in total SOD activities and mRNA expression levels of the liver antioxidant genes, although the effects on growth performance was negligible.

Doubts and difficulties in studying blood pressure variability.

The blood pressure (BP) fluctuation was first noticed in the 18th century. However, its clinical significance did not get attention until recent years. The increase in BP variability (BPV) is possibly more valuable than the increase in BP level for predicting damages in target organs. Moreover, attenuating BPV is more important than decreasing the BP level. However, the concept of BPV was not used in any related guideline for diagnosing, defining, and grading the risk of hypertension, which is due to the understanding of BPV is not profound, and blind areas and misunderstanding still exist in the definition, features, and classification of BPV. In this paper, the doubts and difficulties in studying BPV are analyzed, which may conduce to understand BPV and thus help for the clinical diagnosis and treatment of hypertension.

Effects of feed supplemented with fermented pine needles (Pinus ponderosa) on growth performance and antioxidant status in broilers.

The objective of this study was to compare the effects of Aspergillus niger-fermented pine needles and nonfermented pine needles on growth performance and antioxidant capacity in broiler chicks. In total, 300 1-day-old broiler chicks were randomly allocated to 5 dietary treatments, which were then denoted as the control treatment (basal diet); the nonfermented treatment (containing 0.3% and 0.6% nonfermented treatment, respectively, in the starter and grower phase); or the fermented 1, fermented 2, or fermented 3 treatments. The fermented 1, fermented 2, and fermented 3 treatments contained 0.1, 0.3, and 0.5% fermented treatment, respectively, in the starter phase and 0.2, 0.6, and 1.0% fermented treatment, respectively, in the growth phase for 42 d. The results showed that fermentation treated supplementation had no adverse effect on the growth performance of broilers at 42 d of age. The activity of total nitric oxide synthase was significantly (P<0.05) decreased in the fermented treatment compared with the control and nonfermented treatments in broilers at 21 d of age. Compared with the control, broilers had higher (P<0.05) total superoxide dismutase activities and total antioxidant capacity when they were provided with either the fermented 2 or fermented 3 diet. The malondialdehyde content was significantly (P<0.05) decreased in the fermented 2 and fermented 3 treatments compared with the control and nonfermented treatments. It was concluded that the addition of fermented treatment to the diet could improve antioxidant capacity in broilers, as evidenced by the decrease in malondialdehyde and the increase in total superoxide dismutase activities; however, the effect of fermentation treatment on growth performance was negligible.

Cruciferous vegetables consumption and the risk of female lung cancer: a prospective study and a meta-analysis.

BACKGROUND: Epidemiological studies evaluating the association between cruciferous vegetables (CVs) intake and female lung cancer risk have produced inconsistent results. PATIENTS AND METHODS: This study followed 74 914 Chinese women aged 40-70 years who participated in the Shanghai Women's Health Study. CV intake was assessed through a validated food-frequency questionnaire (FFQ) at baseline and reassessed during follow-up. Hazard ratios (HRs) and 95% confidence interval (CIs) were estimated by using Cox proportional hazards models. Furthermore, we carried out a meta-analysis of all observational studies until December 2011. RESULTS: After excluding the first 2 years of follow-up, 417 women developed lung cancer over a mean of 11.1 years of follow-up. An inverse association of borderline statistical significance was observed between CV consumption and female lung cancer risk, with HR for the highest compared with the lowest quartiles of 0.73 (95% CI 0.54-1.00, P trend = 0.1607). The association was strengthened in analyses restricting to never smokers, with the corresponding HR of 0.59 (95% CI 0.40-0.87, P trend = 0.0510). The finding of an inverse association between CV intake and lung cancer risk in women was supported by our meta-analysis of 10 included studies. CONCLUSIONS: Our study suggests that CV consumption may reduce the risk of lung cancer in women, particularly among never smokers.