Germline variants of DNA repair and immune genes in lymphoma from lymphoma-cancer families.

The genetic predisposition to lymphoma is not fully understood. We identified 13 lymphoma-cancer families (2011-2021), in which 27 individuals developed lymphomas and 26 individuals had cancers. Notably, male is the predominant gender in lymphoma patients, whereas female is the predominant gender in cancer patients (p = .019; OR = 4.72, 95% CI, 1.30-14.33). We collected samples from 18 lymphoma patients, and detected germline variants through exome sequencing. We found that germline protein truncating variants (PTVs) were enriched in DNA repair and immune genes. Totally, we identified 31 heterozygous germline mutations (including 12 PTVs) of 25 DNA repair genes and 19 heterozygous germline variants (including 7 PTVs) of 14 immune genes. PTVs of ATM and PNKP were found in two families, respectively. We performed whole genome sequencing of diffuse large B cell lymphomas (DLBCLs), translocations at IGH locus and activation of oncogenes (BCL6 and MYC) were verified, and homologous recombination deficiency was detected. In DLBCLs with germline PTVs of ATM, deletion and insertion in CD58 were further revealed. Thus, in lymphoma-cancer families, we identified germline defects of both DNA repair and immune genes in lymphoma patients.

Comparison of Outcomes between Stent Retriever Combined with Contact Aspiration and Contact Aspiration Alone in Patients without Hyperdense Artery Sign/Susceptibility Vessel Sign.

PURPOSE: To examine the relationship between hyperdense artery sign (HAS)/susceptibility vessel sign (SVS) and thrombus composition and evaluate the effect of HAS/SVS status on the association between first-line thrombectomy techniques and outcomes in patients with acute anterior circulation large vessel occlusion (LVO). MATERIALS AND METHODS: From January 2018 to June 2021, 103 consecutive patients with acute anterior circulation LVO (75 [63.1%] men; median age, 66 years) who underwent thrombectomy and for whom the removed clot was available for histological analyses were retrospectively reviewed. The presence of HAS and SVS was assessed on unenhanced computed tomography (CT) and susceptibility-weighted imaging, respectively. Association of first-line thrombectomy techniques (stent retriever [SR] combined with contact aspiration [CA] vs CA alone) with outcomes was assessed according to HAS/SVS status. RESULTS: Among the included patients, 55 (53.4%) were HAS/SVS-negative, and 69 (67.0%) underwent first-line SR + CA. Higher relative densities of fibrin/platelets (0.56 vs 0.51; P < .001) and lower relative densities of erythrocytes (0.32 vs 0.42; P < .001) were observed in HAS/SVS-negative patients compared with HAS/SVS-positive patients. First-line SR + CA was associated with reduced odds of distal embolization (adjusted odds ratio, 0.18; 95% CI, 0.04-0.83; P = .027) and a more favorable 90-day functional outcome (adjusted odds ratio, 5.29; 95% CI, 1.06-26.34; P = .042) in HAS/SVS-negative patients and a longer recanalization time (53 vs 25 minutes; P = .025) and higher risk of subarachnoid hemorrhage (24.2% vs 0%; P = .044) in HAS/SVS-positive patients. CONCLUSIONS: Absence of HAS/SVS may indicate a higher density of fibrin/platelets in the thrombus, and first-line SR + CA yielded superior functional outcomes than CA alone in patients with acute LVO without HAS/SVS.

Evaluation method for restoration effect of different sections of small and medium-sized rivers: A case study of the Qingyi River, China.

Due to severe disturbances caused by rapid urbanization and industrialization, river ecosystems have evolved into complex natural-social composite ecosystems. At present, there is no unified evaluation method for the effect of river restoration in China. The existing research fails to fully integrate the "natural-social" characteristics of rivers, and pays less attention to the river section scale, which is not conducive to the development of accurate pollution control work. In this paper, we first put forward the division method of river section type which conforms to the "nature-society" dual attribute characteristics of the river, and divides the river section into "ecological/service/dual" functional "urban/rural" river section. Then a method for evaluating the restoration effect of different river sections based on index weight optimization was proposed. Based on the type of river section, the weights of 17 indexes were optimized, and the common evaluation method of restoration effect-multi-index evaluation method was improved. In addition, the application and verification of the established method were carried out on the main stream of Qingyi River and its typical tributaries. The evaluation results show that only the restoration effect of Baling River decreased from average in 2019 to acceptable in 2021, and ΔH (the change of the mean score of the target factor after repair) decreased from 15.6% to 6.2%. It was found that for the river sections where the repair effect cannot be maintained stably (such as Baling River), the previous methods paid more attention to the overall effect and easily ignored the specific problems. The improved method can identify problems more easily and facilitate timely post-maintenance. To further optimize the repair effect of Qingyi River, it is suggested that the restoration effect should be strengthened from the aspects of pollution source control, water quality improvement, aquatic restoration, continuous monitoring and evaluation. The evaluation results can provide a reference for the design, operation, and maintenance of restoration projects in small and medium-sized rivers.

Effects of reminiscence therapy combined with memory specificity training (RT-MeST) on depressive symptoms in older adults: a randomized controlled trial protocol.

BACKGROUND: Geriatric depression has become a serious public health problem, and reduced autobiographical memory and increased overgeneral memory, as the main cognitive markers of depression, are not only associated with current depressive symptoms but also associated with the onset and course of depression, which can lead to a range of harms. Economic and effective psychological interventions are urgently needed. The aim of this study is to confirm the effectiveness of reminiscence therapy combined with memory specificity training in improving autobiographical memory and depressive symptoms in older adults. METHODS: In this multicentre, single-blind, three-arm parallel randomized controlled study, we aim to enrol 78 older adults aged 65 years or older with a score of ≥ 11 on the Geriatric Depression Scale, and participants will be randomly assigned to either a reminiscence therapy group, a reminiscence therapy with memory specificity training group or a usual care group. Assessments will be conducted at baseline (T0) as well as immediately post-intervention (T1) and 1 (T2), 3 (T3) and 6 (T4) months post-intervention. The primary outcome measure is self-reported depressive symptoms, measured using the GDS. Secondary outcome measures include measures of autobiographical memory, rumination, and social engagement. DISCUSSION: We believe that the intervention will play a positive role in improving autobiographical memory and depressive symptoms in older adults. Poor autobiographical memory is a predictor of depression and a major cognitive marker, and improving autobiographical memory is of great significance in alleviating depressive symptoms in older people. If our program is effective, it will provide a convenient and feasible strategy for further promoting healthy ageing. TRIAL REGISTRATION: ChiCTR2200065446.

Effectiveness of eHealth Interventions on Moderate-to-Vigorous Intensity Physical Activity Among Patients in Cardiac Rehabilitation: Systematic Review and Meta-analysis.

BACKGROUND: Cardiac rehabilitation is a class IA recommendation for patients with cardiovascular diseases. Physical activity is the core component and core competency of a cardiac rehabilitation program. However, many patients with cardiovascular diseases are failing to meet cardiac rehabilitation guidelines that recommend moderate-to-vigorous intensity physical activity. OBJECTIVE: The major objective of this study was to review the evidence of the effectiveness of eHealth interventions in increasing moderate-to-vigorous intensity physical activity among patients in cardiac rehabilitation. The secondary objective was to examine the effectiveness of eHealth interventions in improving cardiovascular-related outcomes, that is, cardiorespiratory fitness, waist circumference, and systolic blood pressure. METHODS: A comprehensive search strategy was developed, and a systematic search of 4 electronic databases (PubMed, Web of Science, Embase, and Cochrane Library) was conducted for papers published from the start of the creation of the database until November 27, 2022. Experimental studies reporting on eHealth interventions designed to increase moderate-to-vigorous intensity physical activity among patients in cardiac rehabilitation were included. Multiple unblinded reviewers determined the study eligibility and extracted data. Risk of bias was evaluated using the Cochrane Collaboration Tool for randomized controlled trials and the Cochrane Effective Practice and Organization of Care group methods for nonrandomized controlled trials. A random-effect model was used to provide the summary measures of effect (ie, standardized mean difference and 95% CI). All statistical analyses were performed using Stata 17. RESULTS: We screened 3636 studies, but only 29 studies were included in the final review, of which 18 were included in the meta-analysis. The meta-analysis demonstrated that eHealth interventions improved moderate-to-vigorous intensity physical activity (standardized mean difference=0.18, 95% CI 0.07-0.28; P=.001) and vigorous-intensity physical activity (standardized mean difference=0.2, 95% CI 0.00-0.39; P=.048) but did not improve moderate-intensity physical activity (standardized mean difference=0.19, 95% CI -0.12 to 0.51; P=.23). No changes were observed in the cardiovascular-related outcomes. Post hoc subgroup analyses identified that wearable-based, web-based, and communication-based eHealth intervention delivery methods were effective. CONCLUSIONS: eHealth interventions are effective at increasing minutes per week of moderate-to-vigorous intensity physical activity among patients in cardiac rehabilitation. There was no difference in the effectiveness of the major eHealth intervention delivery methods, thereby providing evidence that in the future, health care professionals and researchers can personalize convenient and affordable interventions tailored to patient characteristics and needs to eliminate the inconvenience of visiting center-based cardiac rehabilitation programs during the COVID-19 pandemic and to provide better support for home-based maintenance of cardiac rehabilitation. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42021278029; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278029.

Discovery of novel HPPD inhibitors: Virtual screening, molecular design, structure modification and biological evaluation.

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD, a Fe(II)/α-ketoglutarate dependent oxygenases), is a popular herbicide target. In this work, two pharmacophore models based on common molecular characteristics (HipHop) and receptor-ligand complex (CBP) were generated for virtual screening for HPPD inhibitors. About 1,000,000 molecules containing diketone structure from PubChem were filtered by Lipinski's rules to build a 3D database. Then the database was screened through combining HipHop model, CBP model, ADMET (absorption, distribution, metabolism, excretion and toxicity) prediction and molecular docking. Subsequently, based on the specific binding mode and affinity of HPPD inhibitors, 4 molecules with high -CDOCKER energy, good aqueous solubility and human safety predicative properties values were screened. From the screening results and combined with previous work, three novel HPPD inhibitors were designed and synthesized through fragment splicing and bioisosterism strategies. Compound IV-a exhibited similar inhibition of Arabidopsis thaliana HPPD (AtHPPD) and herbicidal activity as mesotrione. Crop selectivity showed that compound IV-a had better crop safety than mesotrione. Comparing the molecular properties, ADMET and molecular docking studies indicated that compounds IV-a exhibited better properties than mesotrione, which could be further modified as novel HPPD inhibitor herbicides.

Diazabicyclo derivatives as safeners protect cotton from injury caused by flumioxazin.

Flumioxazin, a protoporphyrinogen oxidase (PPO; EC 1.3.3.4) inhibitor, has been used in soybean, cotton, grapes, and many other crops to control broad leaf weeds. Unfortunately, it can cause damage to cotton. To ameliorate phytotoxicity of flumioxazin to cotton, this work assessed the protective effects of diazabicyclo derivatives as potential safeners in cotton. A bioactivity assay proved that the phytotoxicity of flumioxazin on cotton was alleviated by some of the compounds. In particular, the activity of glutathione S-transferases (GSTs) was significantly enhanced by Compound 32, which showed good safening activity against flumioxazin injury. The physicochemical properties and absorption, distribution, metabolism, excretion and toxicity (ADMET) predictions proved that the pharmacokinetic properties of Compound 32 are similar to those of the commercial safener BAS 145138. The present work demonstrated that diazabicyclo derivatives are potentially efficacious as herbicide safeners, meriting further investigation.

Arterial blood gas analysis aids early differential diagnosis and treatment of primary and secondary hypokalaemic periodic paralysis.

This study aimed to examine changes in electrolytes and acid-base status in primary and secondary hypokalaemic periodic paralysis (HypoPP), which will help early differential diagnosis of HypoPP. A total of 64 HypoPP patients were enrolled and relevant data from clinical records was collected. Overall, 64 patients (mean age 28.2±7.3 years) of which 58(91%) were males, with 39, 11 and 14 patients, respectively, diagnosed as primary HypoPP, thyrotoxic HypoPP, and other secondary HypoPPs at discharge, were assessed. Those with HypoPP secondary to conditions other than hyperthyroidism were more likely to develop acid-base imbalance (p<0.001); they had higher pH (p=0.046) and HCO3 levels (p=0.014) at baseline, and needed a higher dose of potassium supplement before the serum potassium level returned to normal (p=0.007) and a longer time to regain full muscle strength (p=0.004), compared with those with primary or thyrotoxic HypoPP. Emergent arterial blood gas analysis may aid early differential diagnosis of patients with primary and secondary HypoPP.

Distribution of chimeric antigen receptor-modified T cells against CD19 in B-cell malignancies.

BACKGROUND: The unprecedented efficacy of chimeric antigen receptor T (CAR-T) cell immunotherapy of CD19+ B-cell malignancies has opened a new and useful way for the treatment of malignant tumors. Nonetheless, there are still formidable challenges in the field of CAR-T cell therapy, such as the biodistribution of CAR-T cells in vivo. METHODS: NALM-6, a human B-cell acute lymphoblastic leukemia (B-ALL) cell line, was used as target cells. CAR-T cells were injected into a mice model with or without target cells. Then we measured the distribution of CAR-T cells in mice. In addition, an exploratory clinical trial was conducted in 13 r/r B-cell non-Hodgkin lymphoma (B-NHL) patients, who received CAR-T cell infusion. The dynamic changes in patient blood parameters over time after infusion were detected by qPCR and flow cytometry. RESULTS: CAR-T cells still proliferated over time after being infused into the mice without target cells within 2 weeks. However, CAR-T cells did not increase significantly in the presence of target cells within 2 weeks after infusion, but expanded at week 6. In the clinical trial, we found that CAR-T cells peaked at 7-21 days after infusion and lasted for 420 days in peripheral blood of patients. Simultaneously, mild side effects were observed, which could be effectively controlled within 2 months in these patients. CONCLUSIONS: CAR-T cells can expand themselves with or without target cells in mice, and persist for a long time in NHL patients without serious side effects. TRIAL REGISTRATION: The registration date of the clinical trial is May 17, 2018 and the trial registration numbers is NCT03528421 .

Tri-ortho-cresyl phosphate exposure leads to low egg production and poor eggshell quality via disrupting follicular development and shell gland function in laying hens.

Tri-ortho-cresyl phosphate (TOCP) has been used commercially as a plasticizer and a flame retardant, which has been reported to cause multiple toxicities in humans and other animals. However, the effect of TOCP on female reproductive system is still unclear. The aim of this investigation was to evaluate the reproductive toxicity of TOCP in female avian and investigate its molecular mechanism. In the current study, 50 adult hens were given a single oral dose of TOCP (750 mg/kg). Egg laid by the hens were harvested and counted. Egg quality is assessed by determining the shell strength and thickness. Samples of ovary, shell gland, and serum were collected on day 0, 2, 7, and 21 after the administration. The morphological and pathological changes in tissues were examined. Cell death, follicular development, and steroidogenesis were determined to assess the toxicity of TOCP on laying hens. The results showed that egg production, egg weight, and eggshell strength significantly decreased after TOCP exposure. The calcium levels in serum and eggshell decreased and the expression levels of the eggshell formation-related genes calbindin-D28k (CaBP-D28k) and carbonic anhydrase 2 (CA2) were downregulated. The inhibitory effects of TOCP on follicular development and steroidogenesis were observed with changes in the levels of the related proteins such as forkhead box O1 (FoxO1) and mothers against decapentaplegic homolog 2/3 (Smad2/3). Cell death was identified, which might lead to follicular development disorder. Taken together, TOCP reduced the quantity and quality of the eggs laid by the hens through disrupting follicular development, steroidogenesis, and shell gland function.

Quinoxaline derivatives as herbicide safeners by improving Zea mays tolerance.

Isoxaflutole (IXF), a 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor, causes injury to crops leading to reductions in grain yield. In order to solve the phytotoxicity caused by IXF, the present work evaluated the protective response of the substituted quinoxaline derivatives as potential safeners on Zea mays. The bioassay results showed that all of the test compounds displayed protection against IXF. In particular, safener I-6 exhibited excellent safener activity against IXF injury via enhancing glutathione (GSH) content, glutathione S transferases (GSTs) and cytochrome P450 monooxygenases (CYP450) activity. The tested compounds induced the activity of CYP450 and GSTs in Z. mays. The physicochemical properties and ADMET properties of safener I-6, benoxacor and diketonitrile (DKN, IXF metabolite) were compared to predict pharmaceutical behavior. The present work demonstrates that the safener I-6 could be considered as a potential candidate for developing novel safeners in the future.

On the compromise between noise reduction and speech/noise spatial information preservation in binaural speech enhancement.

Spatial information is important for human perception of speech and sound signals. However, this information is often either distorted or completely neglected in noise reduction because it is challenging, to say the least, to achieve optimal noise reduction and accurate spatial information preservation at the same time. This paper studies the problem of binaural speech enhancement. By jointly diagonalizing the speech and noise correlation matrices, we present a method to construct the noise reduction filter as a linear combination of different eigenvectors, which span a certain subspace of the entire space. A different dimension of the subspace gives a different trade-off between noise reduction and speech/noise spatial information preservation. On the one side, if the dimension is equal to 1, maximum noise reduction is achieved but at the price of significant spatial information distortion. On the other extreme, if the dimension of the subspace is equal to that of the entire space, spatial information is accurately preserved but at the cost of no noise reduction. Therefore, one can achieve different levels of compromises between the amount of noise reduction and the level of speech/noise spatial information preservation by adjusting the dimension of the used subspace.

[Protective effect of ethyl acetate extract from Bidens bipinnata on hepatocyte damage induced by endoplasmic reticulum stress].

To explore the protective effect and mechanism of ethyl acetate extract from Bidens bipinnata on hepatocyte damage induced by endoplasmic reticulum stress. Tunicamycin was used to establish the damage model in L02 cells. Methyl thiazolyl tetrazolium(MTT) colorimetric assay was used to investigate the survival rate of ethyl acetate extract from B. bipinnata in L02 cells injury induced by endoplasmic reticulum stress; the protein expressions of endoplasmic reticulum stress-related molecule glucose regulated protein 78(GRP78), PKR-like ER kinase(PERK), eukaryotic initiation factor-2(eIF2α), activating transcription factor 4(ATF4), C/EBP homologous protein(CHOP), B-cell CLL/lymphoma 2(Bcl-2), Bal-2 associated X apoptosis regulator(Bax) were examined by Wes-tern blot. The expressions of the above proteins were also detected after endoplasmic reticulum stress inhibitor(4-phenyl butyric acid) and CHOP shRNA-mediated knockdowns were added. The expressions of GRP78, PERK, CHOP in L02 cells were observed by immunofluorescence method. The results showed that ethyl acetate extract from B. bipinnata could significantly increase the survival rate of L02 cell injury caused by endoplasmic reticulum stress in a dose and time-dependent manner(P<0.05 or P<0.01). The expression levels of GRP78, PERK, eIF2α, ATF4, CHOP and Bax in the drug treatment groups were significantly down-regulated(P<0.05 or P<0.01), while Bcl-2 was significantly up-regulated(P<0.01). After endoplasmic reticulum stress inhibitor and CHOP shRNA-mediated knockdowns were added, the expression levels of GRP78, PERK, eIF2α, ATF4, CHOP, Bax in the drug treatment groups were significantly down-regulated(P<0.01), whereas Bcl-2 was significantly up-regulated(P<0.01). Immunofluorescence results showed that the expressions of GRP78, PERK, CHOP were consistent with the Western blot method. In conclusion, ethyl acetate extract from B. bipinnata has a significant protective effect on the damage of L02 cells caused by endoplasmic reticulum stress. The mechanism may be related to the inhibition of endoplasmic reticulum stress and the down-regulation of apoptosis in cells through the PERK/eIF2α/ATF4/CHOP signaling pathway.

High-dose chemotherapy followed by autologous stem cell transplantation for patients with refractory/relapsed classical Hodgkin lymphoma: a single center experience from China.

To evaluate the outcomes of refractory/relapsed cHL patients after high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) in Beijing Cancer hospital and to identify the prognostic risk factors. We retrospectively analyzed 115 relapsed/refractory cHL patients who accepted HDCT and ASCT in our cancer center and had complete follow-up data from April 2000 to May 2017. Ages of these 115 patients at ASCT ranged from 14 to 63 (median age 28). Forty-four (38.3%) patients achieved CR and 50 (43.5%) patients achieved PR before ASCT. Thirty-seven (48.7%) patients of those 76 patients who did PET-CT before ASCT had negative PET-CT scans. The median follow-up time was 72 months. A total of 23 patients died in our study. The 5-year OS and PFS rates of all patients after ASCT were 78.7% and 53%, respectively. The 5-year OS rates after ASCT of patients who were in CR or PR or less than PR status before ASCT were 92.8%, 68.2%, and 76.2%, respectively (log-rank = 2.913, p = 0.233). And their 5-year PFS rates after ASCT were 69.2%, 54.2%, and 18.5%, respectively (log-rank = 13.615, p = 0.001). Univariate analysis revealed that ECOG (p = 0.010; hazard ratio = 1.578), disease status before ASCT (CR: p = 0.001; hazard ratio = 0.227) and after ASCT (CR: p < 0.001; hazard ratio = 0.154), and PET-CT results after ASCT (p = 0.023; hazard ratio = 0.438) significantly impact patients' PFS while number of pretransplant salvage chemotherapy (p = 0.037; hazard ratio = 2.521), radiotherapy (p = 0.046; hazard ratio = 0.423), and disease status after ASCT (CR: p = 0.010; hazard ratio = 0.197) significantly affected patients' OS. Multivariate analysis shown only disease status before ASCT (p = 0.002) had significant impact on PFS and disease status after ASCT (p = 0.021) had significant impact on OS. R/R HL patients can still obtain long-term PFS after HDCT and ASCT and disease status before ASCT was the most significant prognostic factor for PFS.

Enhanced organic matter decomposition in sediment by Tubifex tubifex and its pathway.

The role of Tubifex tubifex in organic matter (OM) decomposition in aquatic ecosystems has been widely studied, but considerable uncertainties exist in terms of the effect mechanism. The effect of T. tubifex on sediment OM decomposition in laboratory-scale microcosms was quantified, and possible pathways were identified. In the first 7 days of the decomposition of OM mixed in sediment, no significant effect of T. tubifex on organic matter loss (OML) was observed for both low- and high-OM treatments; meanwhile, from day 7-60, T. tubifex addition significantly improved OML from 55.0%-57.5% to 71.8%-77.7% in the low-OM treatments and from 55.5%-56.6% to 64.1%-68.7% in the high-OM treatments. The enhanced OML observed with T. tubifex was mainly due to the promoted decomposition of refractory organic components, e.g., cellulose, hemicellulose and lignin. The proportion of refractory components in the gut of T. tubifex was significantly lower than that in the sediments (p < 0.01), indicating a pathway corresponding to the ingestion and digestion of refractory components by T. tubifex. Although T. tubifex reduced the water dissolved oxygen (DO) by increasing the water chemical oxygen demand (COD), the oxygen supply was improved by T. tubifex, and this could be affected by the increase in the relative abundance of aerobic to anaerobic bacteria in the sediments. T. tubifex significantly increased the diversity of the bacterial and fungal communities in the sediments. Moreover, the community structure of bacteria and fungi was substantially different between gut and sediment. Therefore, multiple pathways of the effect of T. tubifex on OM decomposition were established, and the results have great significance for the artificial manipulation of OM circulation using T. tubifex and the restoration of damaged aquatic ecosystems.

Metagenomic Analysis Revealed that the Terrestrial Pollutants Override the Effects of Seasonal Variation on Microbiome in River Sediments.

Researching the structure and function of sediment microbiome contribute to understanding the response of microbiome to external disturbances. However, seasonal changes in sediment microbiome with different terrestrial pollutants input have not yet been clearly understood. Metagenomic sequencing was used to evaluate the effects of seasonal variations and different land use types on sediment microbiome. Results showed that the differences in structure and functions of sediment microbiome among different land use types were obviously greater than different seasons. This indicated that the terrestrial pollutants weakened the effects of seasonal variations on shaping the sediment microbiome. The significant differences in sediment properties under the input of different terrestrial pollutants was observed, but no obvious differences between seasons, which may be the reason why terrestrial pollutants override the effects of seasonal variation on the sediment microbiome. Overall, the results extended our understanding of the impacts of seasonal variation and terrestrial pollutants on river sediment microbiome.

[Effect and mechanism of Bidens pilosa decoction on non-alcoholic fatty liver induced by high fat and high glucose in mice].

This study aimed to investigate the effect and possible mechanism of Bidens pilosa decoction on non-alcoholic fatty liver disease(NAFLD) induced by high fat and high glucose in mice. Bald/c mice were randomly divided into normal group, model group, metformin(200 mg·kg~(-1)) treatment group, Bidens pilosa decoction(10 g·kg~(-1)) treatment group, metformin and B. pilosa decoction(100 mg·kg~(-1)+5 g·kg~(-1)) treatment group. Except for the normal group, mice in the other four groups were fed with high-fat and high-glucose diet for 8 weeks to establish the non-alcoholic fatty liver model. After 4 weeks of treatment, blood was collected from the eyeballs, the mice were sacrificed, and relevant indicators were detected. The results showed that compared with the model group, blood lipid and blood glucose levels of each treatment group were significantly lower(P<0.05); HE staining results showed that liver pathological damage in each treatment group was significantly improved; oil red O staining results showed fat distribution in each treatment group significantly reduced(P<0.01); immunohistochemical staining showed that glucose regulated the protein expression of protein 78(GRP78) in liver tissues of each treatment group was also significantly reduced(P<0.01); Western blot results showed that endoplasmic reticulum stress signal pathway-related factors GRP78, phosphorylated-protein kinase R-like ER kinase(p-PERK), eukaryotic translation-initiation factor 2α(eIF2α), activating transcription factor 4(ATF4), C/EBP homologous protein(Chop), inositol requiring 1α(IRE1α), and cleaved-cysteinyl aspartate specific proteinase 12(cleaved-caspase-12) were significantly reduced(P<0.01). The results of the combined drug treatment group were better than those of the single drug treatment group. These results showed that B. pilosa decoction had the effect in improving non-alcoholic fatty liver, and its mechanism may be related to the down-regulation of the expression of endoplasmic reticulum stress(ERS)-related factors, and the reduction of the apoptosis of hepatocytes caused by ERS and the down-regulation of blood lipid and blood glucose levels.

Apoptosis in HepaRG and HL-7702 cells inducted by polyphyllin II through caspases activation and cell-cycle arrest.

Rhizoma Paridis, a traditional Chinese medicine, has shown promise in cancer prevention and therapy. Polyphyllin II is one of the most significant saponins in Rhizoma Paridis and it has toxic effects on kinds of cancer cells. However, our results in this study proved that the polyphyllin II has hepatotoxicity in vitro through caspases activation and cell-cycle arrest. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide results indicated polyphyllin II inhibited proliferation, induced apoptosis in HepaRG cells and HL-7702 cells and showed a concentration and time-dependent. Then, we selected the innovative cell model-HepaRG cells to explore the mechanism of hepatotoxicity. Our data showed the reactive oxygen species (ROS) increased and the mitochondrial membrane potential decreased in HepaRG cells after administration of polyphyllin II. Besides, with the increase of concentration, the release of lactate dehydrogenase increased and the S phase of the cell cycle was arrested. Nevertheless, when pretreatment with antioxidant N-acetylcysteine, apoptotic cells decreased significantly, inhibited the production of ROS and improved the decrease of membrane potential in HepaRG cells. Moreover, polyphyllin II treatment increased levels of Fas, Bax, cytochrome c, activated caspase-3, -8, -9, cleaved poly(ADP-ribose) polymerase and decreased Bcl-2 expression levels. Finally, we identified two signal pathways of apoptosis induced by polyphyllin II including the death receptor pathway and the mitochondria pathway. This study confirmed the hepatotoxicity of the polyphyllin II in vitro, which has never been discovered and gave a wake-up call for the clinical application of Rhizoma Paridis.

Near-infrared fluorescent probe for selective detection of H2S and its application in living animals.

In this study, a novel near-infrared fluorescent off-on probe for H2S based on seminaphthorhodafluor fluorophore is designed and constructed, which could be used in detection with 121-fold (23-fold) fluorescent (absorbance) enhancement at 630 nm (572 nm), fast responsiveness (completed within 5 min), high sensitivity, and lower cellular autofluorescence interference. Based on these excellent optical properties, the probe was employed to monitor H2S in red wine samples with satisfactory results. Moreover, the probe was successfully applied for monitoring and imaging H2S quantitatively in Hela cells and live athymic nude mice, indicating its potential application in biological science.

Treatment Strategies and Prognostic Factors of Primary Gastric Diffuse Large B Cell Lymphoma: A Retrospective Multicenter Study of 272 Cases from the China Lymphoma Patient Registry.

Background: The respective and combinatorial roles of surgery, Rituximab and chemotherapy in primary gastric diffuse large B cell lymphoma (PGDLBCL) therapy remained unclear. The purpose of the study was to evaluate present treatment strategies and prognostic factors of PGDLBCL. Methods: 272 cases (from 1994-1 to 2015-12) were retrospectively analyzed. According to the therapy regimen, patients were classified into four groups: chemotherapy (C), chemotherapy + surgery (C+S), Rituximab + chemotherapy (R+C), and Rituximab + chemotherapy + surgery (R+C+S). Results: The 3-year progression-free survival (PFS) and 3-year overall survivals (OS) of the entire cohort were 77.0% and 81.2% respectively (median follow-up time: 44.3 months). Survival of surgery-treated patients was superior to the survival of those receiving drug therapy alone (PFS: 82.6% vs. 74.7%, p=0.015; OS: 87.8% vs. 78.6%, p=0.036). Rituximab showed significant clinical benefit in OS (87.1% vs. 75.0%, p=0.007), especially in advanced-stage or high risk (IPI 3-5) patients. Group C had the lowest PFS and OS among the four groups, while the survival of other three groups were similar (Group C vs. Group C+S vs. Group R+C vs. Group R+C+S: 3-year PFS: 67.2% vs. 81.4% vs. 81.2% vs. 81.8%, p=0.002; 3-year OS: 68.4% vs. 85.4% vs. 87.2% vs. 88.6%, p<0.001). Multivariate analysis showed that IPI and therapy regimens were highly predictive for both PFS and OS. Conclusions: Our results suggested that the combinations of chemotherapy and surgery, or chemotherapy and Rituximab, are superior to other treatment strategies for PGDLBCL. IPI and therapy regimens are independent predictors of outcomes. Future prospective trial is warranted.