Safety and efficacy of onradivir in adults with acute uncomplicated influenza A infection: a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial.

BACKGROUND: Onradivir (ZSP1273) is a novel anti-influenza A virus inhibitor. Preclinical studies show that onradivir can inhibit influenza A H1N1 and H3N2 replication and increase the survival rate of infected animals. In this study, we aimed to evaluate the safety and efficacy of three onradivir dosing regimens versus placebo in outpatients with acute uncomplicated influenza A virus infection. METHODS: We did a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial at 20 clinical sites in China. Eligible participants were adults (18-65 years) with an influenza-like illness screened by rapid antigen testing at the first clinical visit, had the presence of a fever (axillary temperature ≥38·0°C), and had the presence of at least one moderate systemic and one respiratory symptom within 48 h of symptom onset. Patients were excluded if they were pregnant, allergic to onradivir, or had received any influenza antiviral medication within 7 days before enrolment. Participants were randomly assigned (1:1:1:1) into four groups by an interactive web response system: onradivir 200 mg twice per day group, onradivir 400 mg twice per day group, onradivir 600 mg once per day group, and a matching placebo group. A 5-day oral treatment course was initiated within 48 h after symptoms onset. The primary outcome was the time to alleviate influenza symptoms in the modified intention-to-treat population. Safety was a secondary outcome. We evaluated the patients' self-assessed severity of seven influenza symptoms on a 4-point ordinal scale, and the treatment-emergent adverse events in all patients. This trial is registered with ClinicalTrials.gov, number NCT04024137. FINDINGS: Between Dec 7, 2019, and May 18, 2020, a total of 205 patients were screened; of whom, 172 (84%) were randomly assigned to receive onradivir (n=43 in the 200 mg twice per day group; n=43 in the 400 mg twice per day group; and n=43 in the 600 mg once per day group), or placebo (n=42). Median age was 22 years (IQR 20-26). All three onradivir groups showed decreased median time to alleviate influenza symptoms (46·92 h [IQR 24·00-81·38] in the 200 mg twice per day group, 54·87 h [23·67-110·62] in the 400 mg twice per day group, and 40·05 h [17·70-65·82] in the 600 mg once per day) compared with the placebo group (62·87 h [36·40-113·25]). The median difference between the onradivir 600 mg once per day group and the placebo group was -22·82 h (p=0·0330). The most frequently reported treatment-emergent adverse event was diarrhoea (71 [42%] of 171), ranging from 33-65% of the patients in onradivir-treated groups compared with 10% in the placebo group; no serious adverse events were observed. INTERPRETATION: Onradivir showed a safety profile comparable to placebo, as well as higher efficacy than placebo in ameliorating influenza symptoms and lowering the viral load in adult patients with uncomplicated influenza infection, especially the onradivir 600 mg once per day regimen. FUNDING: National Multidisciplinary Innovation Team Project of Traditional Chinese Medicine, National Natural Science Foundation of China, Guangdong Science and Technology Foundation, Guangzhou Science and Technology Planning Project, Emergency Key Program of Guangzhou Laboratory, Macao Science and Technology Development Fund, and Guangdong Raynovent Biotech.

Discovery of proqodine A derivatives with antitumor activity targeting NAD(P)H: quinone oxidoreductase 1 and nicotinamide phosphoribosyltransferase.

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD+), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD+ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD+ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.

The distinct plastisphere microbiome in the terrestrial-marine ecotone is a reservoir for putative degraders of petroleum-based polymers.

Research into plastic-degrading bacteria and fungi is important for understanding how microorganisms can be used to address the problem of plastic pollution and for developing new approaches to sustainable waste management and bioplastic production. In the present study, we isolated 55 bacterial and 184 fungal strains degrading polycaprolactone (PCL) in plastic waste samples from Dafeng coastal salt marshes, Jiangsu, China. Of these, Jonesia and Streptomyces bacteria also showed potential to degrade other types of petroleum-based polymers. The metabarcoding results proved the existence of plastisphere as a distinct ecological niche regardless of the plastic types where 27 bacterial and 29 fungal amplicon sequence variants (ASVs) were found to be significantly (p < 0.05) enriched, including some belonging to Alternaria (Ascomycota, Fungi) and Pseudomonas (Gammaproteobacteria, Bacteria) that were also mined out by the method of cultivation. Further assembly analyses demonstrated the importance of deterministic processes especially the environmental filtering effect of carbon content and pH on bacteria as well as the carbon and cation content on fungi in shaping the plastisphere communities in this ecosystem. Thus, the unique microbiome of the plastisphere in the terrestrial-marine ecotone is enriched with microorganisms that are potentially capable of utilizing petroleum-based polymers, making it a valuable resource for screening plastic biodegraders.

Ginkgo biloba extract ameliorates atherosclerosis via rebalancing gut flora and microbial metabolism.

The Ginkgo biloba leave extract (GbE) is widely applied in the prevention and treatment of atherosclerotic cardiovascular diseases in clinical practice. However, its mechanism of actions has not been totally elucidated. In this study, we confirmed the beneficial effects of GbE in alleviating hypercholesterolemia, inflammation and atherosclerosis in Ldlr-/- mice, which were fed 12 weeks of Western diet (WD). Moreover, 16S rRNA sequencing revealed that GbE treatment reshaped the WD-perturbed intestinal microbiota, particularly decreased the Firmicutes/Bacteroidetes ratio and elevated the abundance of Akkermansia, Alloprevotella, Alistipes, and Parabacteroides. Furthermore, GbE treatment downregulated the intestinal transcriptional levels of proinflammatory cytokines and enhanced the expression of tight junction proteins, exerting the roles of attenuating the intestinal inflammation as well as repairing the gut barrier. Meanwhile, the targeted metabolomic analysis displayed that GbE treatment significantly reversed the dysfunction of the microbial metabolic phenotypes, including promoting the production of short chain fatty acids, indole-3-acetate and secondary bile acids, which were correlated with the atherosclerotic plaque areas. Finally, we confirmed GbE-altered gut microbiota was sufficient to alleviate atherosclerosis by fecal microbiota transplantation. In summary, our findings provide important insights into the pharmacological mechanism underlying the antiatherogenic efficacy of GbE.

Towards high-performance sustainable polymers via isomerization-driven irreversible ring-opening polymerization of five-membered thionolactones.

The development of sustainable polymers that possess useful material properties competitive with existing petroleum-derived polymers is a crucial goal but remains a formidable challenge for polymer science. Here we demonstrate that irreversible ring-opening polymerization (IROP) of biomass-derived five-membered thionolactones is an effective and robust strategy for the polymerization of non-strained five-membered rings-these polymerizations are commonly thermodynamically forbidden under ambient conditions, at industrially relevant temperatures of 80-100 °C. Computational studies reveal that the selective IROP of these thionolactones is thermodynamically driven by S/O isomerization during the ring-opening process. IROP of γ-thionobutyrolactone, a representative non-strained thionolactone, affords a sustainable polymer from renewable resources that possesses external-stimuli-triggered degradability. This poly(thiolactone) also exhibits high performance, with its key thermal and mechanical properties comparing well to those of commercial petroleum-based low-density polyethylene. This IROP strategy will enable conversion of five-membered lactones, generally unachievable by other polymerization methods, into sustainable polymers with a range of potential applications.

Financial and social impacts of drug price changes: Evidence from 2017 healthcare reform in Liaoning Province, China.

Healthcare reform was launched in China in 2017 to reduce the financial burden on both patients and the government by terminating the 15% markup on drug prices at public hospitals. To evaluate this reform's impacts, we conduct a quantitative study based on the operational data from one of the top 10 hospitals in Liaoning, China. Specifically, we utilize log-linear and logistic regression models to examine the policy's impacts on patients' total healthcare expenditures and the hospital's adjustments of its offering list that consists of western medicine (WM), traditional Chinese medicine (TCM) and non-medicine (NM). We find that the reform effectively alters the patients' spending structure and the hospital's profit model: (1) it decreases patients' average per-visit expenditure on WM and TCM while increases their average NM expenditure; (2) it differently affects patients from various socioeconomic groups and leaves space to target on groups that may demand extra financial and healthcare assistance; (3) it slows down the hospital's revenue increase and incentivizes the hospital to shift the WM revenue from margin-driven to volume-driven and to weigh more on NM revenue and (4) it encourages the hospital to keep WMs with steady price and drop WMs whose price keeps rising.

Application Potential of Plant-Derived Medicines in Prevention and Treatment of Platinum-Induced Peripheral Neurotoxicity.

As observed with other chemotherapeutic agents, the clinical application of platinum agents is a double-edged sword. Platinum-induced peripheral neuropathy (PIPN) is a common adverse event that negatively affects clinical outcomes and patients' quality of life. Considering the unavailability of effective established agents for preventing or treating PIPN and the increasing population of cancer survivors, the identification and development of novel, effective interventions are the need of the hour. Plant-derived medicines, recognized as ideal agents, can not only help improve PIPN without affecting chemotherapy efficacy, but may also produce synergy. In this review, we present a brief summary of the mechanisms of platinum agents and PIPN and then focus on exploring the preventive or curative effects and underlying mechanisms of plant-derived medicines, which have been evaluated under platinum-induced neurotoxicity conditions. We identified 11 plant extracts as well as 17 plant secondary metabolites, and four polyherbal preparations. Their effects against PIPN are focused on oxidative stress and mitochondrial dysfunction, glial activation and inflammation response, and ion channel dysfunction. Also, ten clinical trials have assessed the effect of herbal products in patients with PIPN. The understanding of the molecular mechanism is still limited, the quality of clinical trials need to be further improved, and in terms of their efficacy, safety, and cost effectiveness studies have not provided sufficient evidence to establish a standard practice. But plant-derived medicines have been found to be invaluable sources for the development of natural agents with beneficial effects in the prevention and treatment of PIPN.

Comparison of responses of melanocyte lineages from p75(+) and p75(-) human scalp-derived neural crest stem cells under phototherapy.

Phototherapy is an effective therapeutic option in the treatment of vitiligo; however, responses varied among the different types. The underlying mechanism has scarcely been investigated. To investigate and compare the effects of phototherapy on the mutation of melanocyte lineage differentiated from human scalp-derived neural crest stem cells (HS-NCSCs) with p75 neurotrophin receptor expression positive and p75 neurotrophin receptor expression negative group in vitro, the HS-NCSCs were isolated from fetal scalp tissue, which is identified by immunofluorescent staining. The p75(+) and p75(-) cells from HS-NCSCs were isolated by magnetic cell sorting, respectively. The embryonic neural crest stem cell biomarkers were detected by RT-PCR. Narrow-band UVB (NB-UVB) was used to irradiate the cells. Cell proliferation was evaluated by cell count. Tyrosinase, Tyrp1, and Tyrp2 gene expression were measured by quantitative RT-PCR. Tyrosinase and GRCR protein levels were investigated by Western blot analysis. The electrophoretic strip showed that Sox2, Oct4, Sox10, and Nestin of p75(+) HS-NCSCs were brighter than the p75(-) HS-NCSCs. After the same dose radiation with NB-UVB, the cell proliferation of p75(+) group showed less inhibitory rate compared with the p75(-) HS-NCSCs. The tyrosinase mRNA and protein expression of differentiated melanocytes increased significantly in the group of p75(+) HS-NCSCs compared with the p75(-) group. The melanocytic mutation of p75(+) HS-NCSCs increased significantly compared with the p75(-) HS-NCSCs under NB-UVB, which indicated there were more melanocyte precursors in the differentiated cells from p75(+) HS-NCSCs. This may provide new insights for the different repigmentation efficacy of segmental and non-segmental vitiligo.

NB-UVB Induces Melanocytic Differentiation of Human Hair Follicle Neural Crest Stem Cells.

BACKGROUND: Phototherapy is an important method to treat vitiligo. However, it is unclear how phototherapy affects melanocyte precursors and skin neural crest stem cells. OBJECTIVE: To investigate the underlying mechanisms of narrow-band ultraviolet B (NB-UVB) induced melanocyte lineage differentiated from human scalp-derived neural crest stem cells (HS-NCSCs). METHODS: HS-NCSCs were expanded from scalp hair follicles. The c-Kit-/CD57- HS-NCSCs were isolated by cell sorting. Different doses of NB-UVB were used to irradiate these HS-NCSCs. Cell ultrastructure was examined by transmission electron microscope. Melanocyte marker expression was analyzed by Quantitative RT-PCR and Western blot. Cell proliferation and migration were also evaluated. RESULTS: The c-Kit-/CD57- HS-NCSCs expressed embryonic NCSC biomarkers. NB-UVB at a dose of 100 mJ of NB-UVB had little effect on the cell proliferation of differentiated melanocytes from c-Kit-/CD57- HS-NCSCs, while 700 mJ inhibited cell proliferation significantly. The dendritic processes of differentiated melanocytes increased after radiation. The tyrosinase and Melanocortin 1 receptor (Mc1R) expression of differentiated melanocytes increased after NB-UVB exposure. The effect of NB-UVB on tyrosinase expression was modulated by signaling inhibitors H89 and PD98059 as well as Mc1R level in the cells. The migration ability of differentiated melanocytes was enhanced under 100 mJ exposure. CONCLUSION: These data demonstrate that NB-UVB facilitates melanocytic differentiation of the HS-NCSCs and enhances migration of these cells. Mc1R and cAMP pathway play a critical role in NB-UVB induced melanocytic differentiation.

Anti-inflammatory effect of self-emulsifying delivery system containing Sonchus oleraceus Linn extract on streptozotocin-induced diabetic rats.

Edible Sonchus oleraceus Linn is a medicinal plant with many bioactivities such as anti-diabetic activity and anti-inflammatory activity. However, the main bioactive components such as polyphenols in S. oleraceus Linn are poorly absorbed in gastrointestinal tract and rapidly metabolized. Thereby, a self-emulsifying delivery system containing S. oleraceus Linn extracts (SSEDDS) was introduced to evade these problems. Herein, the anti-inflammatory effect of SSEDDS on streptozotocin-induced diabetic rats was investigated. The plasma glucose level was increased and plasma insulin level was decreased in diabetic rats. The levels of NF-κB, TNF-α, and IL-6 in the liver were significantly improved in diabetic rats (p < 0.05). Conversely, daily fed diabetic rats with 100, 200 and 400 mg/kg/day of SSEDS and 1 mg/kg/day metformin for 4 weeks, significantly (p < 0.05) restored all the above mentioned parameters to near normal levels. The immuno-histochemical studies confirmed the anti-inflammatory effects of SSEDDS.

Fructus Psoraleae-Induced Severe Liver Injury and Treatment With Two Artificial Liver Support Systems: A Case Series Study.

To describe the clinical features and outcomes of patients with suspected Fructus Psoraleae (FP)-induced severe liver injury who underwent treatment with two artificial liver support systems (ALSSs). The cases of 12 patients with severe liver injury by FP were enrolled. We evaluated the tolerability of, and changes in biochemical parameters after treatment with plasma exchange combined with hemofiltration and double plasma molecular absorption system, and 6-month follow-up information were collected. The median age of the 12 patients was 60 years and nine (75%) patients were females. All patients had jaundice as the initial symptom. Two ALSS types were used to treat the patients. The group that underwent plasma exchange combined with hemofiltration showed remarkable improvements in ALT, AST, total bilirubin (TB), GGT and international normalized ratio levels (AST, TB, international normalized ratio, P < 0.01; ALT, GGT, P < 0.05), and the levels of AST, ALP, TB, and total bile acid decreased significantly in the double plasma molecular absorption system group after treatment (TB, P < 0.01; AST, ALP, total bile acid P < 0.05). During 6 months of follow-up, two patients died, two became chronic, and eight recovered to normal. FP can cause clinically severe liver injury, characterized by gastrointestinal symptoms and jaundice, which can lead to death or become chronic. Both ALSSs were safe and well tolerated in drug-induced liver injury patients. After ALSS treatment, the levels of biochemical indicators of liver function improved significantly, indicating that ALSS might be beneficial for patients with severe drug-induced liver injury.

Network Pharmacology-Based Pharmacological Mechanism of the Chinese Medicine Rhizoma drynariae Against Osteoporosis.

d_abstr_R Rhizoma drynariae is the main traditional Chinese medicine used for the treatment of osteoporosis, but its anti-osteoporotic targeting mechanism has not been fully elucidated due to the complexity of its active ingredients. In this study, the pharmacological mechanism of action of Rhizoma drynariae against osteoporosis was studied by integrating pharmacological concepts. The pharmacokinetic characteristics of selected major active constituents of Rhizoma drynariae and the SMILES structural similarity were used to predict related targets. A literature search was conducted to identify known osteoporosis treatment targets, which were then combined with the predicted targets to construct the direct or indirect target interaction network map of Rhizoma drynariae against osteoporosis. Finally, data on the key targets of the interactions, ranked according to relevant node parameters obtained through pathway enrichment analysis and screening of key targets and active ingredients of Rhizoma drynariae, were used to perform molecular docking simulation. We screened 16 active ingredients of Rhizoma drynariae, and 7 key targets with direct or indirect effects with a high frequency were obtained. These main pathways were found to play important roles in the PI3k-akt signaling pathway, osteoclast differentiation, Wnt signaling pathway, and estrogen signaling pathway. Molecular docking showed that most active ingredients of Rhizoma drynariae had strong binding efficiency with key targets. Based on network pharmacology, we conclude that Rhizoma drynariae plays an anti-osteoporotic role by directly or indirectly targeting multiple major signaling pathways and influencing the proliferation and differentiation of multiple types of cells.

Apoptotic cell-mimicking gold nanocages loaded with LXR agonist for attenuating the progression of murine systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) constitutes an autoimmune disease characterized by the breakdown of tolerance to self-antigens, sustained production of pathogenic autoantibodies, and damage to multiple organs and tissues. Nanoparticle (NP)-based therapeutics have demonstrated efficacy in attenuating the progression of SLE. However, investigations of nano-drugs that address the crucial initiating factor in the pathogenesis of SLE; e.g., inefficient clearance of apoptotic cells by phagocytes and consequent accumulation of self-antigens, have seldom been reported. Here, an apoptotic cell-mimicking gold nanocage (AuNC)-based nano drug carrier capable of correcting the impaired clearance of apoptotic cells in SLE was rationally designed and generated by conjugating phosphatidylserine (PS) on the surface of liposome-coated AuNCs for liver X receptor (LXR) agonist T0901317 delivery. Notably, PS-lipos-AuNC@T0901317 could efficiently enhance apoptotic cell clearance by elevating the expression of Mer, one of the pivotal phagocytosis-associated receptors on macrophages, resulting in decreased production of anti-dsDNA autoantibodies, reduced inflammatory response, and alleviation of kidney damage in lupus model mice. Additionally, PS-lipos-AuNC could be tracked by photoacoustic imaging for nano drug carrier biodistribution. By addressing the crucial pathogenic factor of SLE, the NP-based delivery system in this study is envisioned to provide a promising strategy to treat this complex and challenging disease.

Screening for Neuraminidase Inhibitory Activity in Traditional Chinese Medicines Used to Treat Influenza.

OBJECTIVE: To screen for influenza virus neuraminidase inhibition and to provide a reference for the clinical treatment of influenza using traditional Chinese medicines (TCM). In this study, 421 crude extracts (solubilized with petroleum ether, ethanol, ethyl acetate, and aqueous solvents) were obtained from 113 TCM. The medicine extracts were then reacted with oseltamivir, using 2'-(4-methylumbelliferyl)-α-D-N-acetylneuraminic acid (MUNANA) as the substrate, to determine influenza virus neuraminidase activity using a standard fluorimetric assay. It was found that Chinese medicine extracts from Pyrola calliantha, Cynanchum wilfordii, Balanophora involucrata and Paeonia delavayi significantly inhibited neuraminidase activity at a concentration of 40 µg/mL. Dose-dependent inhibitory assays also revealed significant inhibition. The IC50 range of the TCM extracts for influenza virus neuraminidase was approximately 12.66-34.85 µg/mL, respectively. Some Chinese medicines have clear anti-influenza viral effects that may play an important role in the treatment of influenza through the inhibition of viral neuraminidase. The results of this study demonstrated that plant medicines can serve as a useful source of neuraminidase (NA) inhibitors and further investigation into the pharmacologic activities of these extracts is warranted.

Personalized Preclinical Trials in BRAF Inhibitor-Resistant Patient-Derived Xenograft Models Identify Second-Line Combination Therapies.

PURPOSE: To test second-line personalized medicine combination therapies, based on genomic and proteomic data, in patient-derived xenograft (PDX) models. EXPERIMENTAL DESIGN: We established 12 PDXs from BRAF inhibitor-progressed melanoma patients. Following expansion, PDXs were analyzed using targeted sequencing and reverse-phase protein arrays. By using multi-arm preclinical trial designs, we identified efficacious precision medicine approaches. RESULTS: We identified alterations previously described as drivers of resistance: NRAS mutations in 3 PDXs, MAP2K1 (MEK1) mutations in 2, BRAF amplification in 4, and aberrant PTEN in 7. At the protein level, re-activation of phospho-MAPK predominated, with parallel activation of PI3K in a subset. Second-line efficacy of the pan-PI3K inhibitor BKM120 with either BRAF (encorafenib)/MEK (binimetinib) inhibitor combination or the ERK inhibitor VX-11e was confirmed in vivo Amplification of MET was observed in 3 PDX models, a higher frequency than expected and a possible novel mechanism of resistance. Importantly, MET amplification alone did not predict sensitivity to the MET inhibitor capmatinib. In contrast, capmatinib as single agent resulted in significant but transient tumor regression in a PDX with resistance to BRAF/MEK combination therapy and high pMET. The triple combination capmatinib/encorafenib/binimetinib resulted in complete and sustained tumor regression in all animals. CONCLUSIONS: Genomic and proteomic data integration identifies dual-core pathway inhibition as well as MET as combinatorial targets. These studies provide evidence for biomarker development to appropriately select personalized therapies of patients and avoid treatment failures. See related commentary by Hartsough and Aplin, p. 1550.

Efficiently engineered cell sheet using a complex of polyethylenimine-alginate nanocomposites plus bone morphogenetic protein 2 gene to promote new bone formation.

Regeneration of large bone defects is a common clinical problem. Recently, stem cell sheet has been an emerging strategy in bone tissue engineering. To enhance the osteogenic potential of stem cell sheet, we fabricated bone morphogenetic protein 2 (BMP-2) gene-engineered cell sheet using a complex of polyethylenimine-alginate (PEI-al) nanocomposites plus human BMP-2 complementary(c)DNA plasmid, and studied its osteogenesis in vitro and in vivo. PEI-al nanocomposites carrying BMP-2 gene could efficiently transfect bone marrow mesenchymal stem cells. The cell sheet was made by culturing the cells in medium containing vitamin C for 10 days. Assays on the cell culture showed that the genetically engineered cells released the BMP-2 for at least 14 days. The expression of osteogenesis-related gene was increased, which demonstrated that released BMP-2 could effectively induce the cell sheet osteogenic differentiation in vitro. To further test the osteogenic potential of the cell sheet in vivo, enhanced green fluorescent protein or BMP-2-producing cell sheets were treated on the cranial bone defects. The results indicated that the BMP-2-producing cell sheet group was more efficient than other groups in promoting bone formation in the defect area. Our results suggested that PEI-al nanocomposites efficiently deliver the BMP-2 gene to bone marrow mesenchymal stem cells and that BMP-2 gene-engineered cell sheet is an effective way for promoting bone regeneration.

[Meta-analysis on elemene injection combined with cisplatin chemotherapeutics in treatment of non-small cell lung cancer].

To research databases of Cochrane library, Web of Science, PubMed, FMJS, CBM, VIP, CNKI and Wanfang Data Konwledge Service Platform by computers as at July 5, 2012, which was supplemented with other search results. The findings were included into randomized controlled trials (RCTs) of elemene injection combined with cisplatin chemotherapeuties in treating small cell lung cancer (NSCLC). Data was separately collected by two researchers for literature quality evaluation, and a Meta analysis was made with RevMan 5. 2 software, in order to assess the efficacy and safety of elemene injection combined with cisplatin chemotherapeutics in treating NSCLC. Totally 11 RCTs or 844 cases were included. Meta analysis results suggested that compared with cisplatin chemotherapy alone, the combination of elemene injection and cisplatin chemotherapeutics showed a higher clinical benefit rate ( OR = 2. 03, 95% CI:1.43-2. 88, P <0. 000 1) and a better quality of life (OR = 3.23, 95% CI:2. 20-4. 74, P <0. 000 01). Besides,the combination could also reduce leucopenia (OR =0. 50, 95% CI:0. 33-0. 76, P <0. 001) , and thrombocytopenia (OR =0. 38, 95% CI:0. 16-0. 85, P <0. 02), increase CD4 (MD = 3.32, 95% C1:2. 94-3.70, P <0. 000 01), and CD4/CD8 (MD = 0. 36, 95% CI:0. 28-0. 44, P < 0. 000 01) , and relieve gastrointestinal reactions such as nausea and vomiting (OR = 0. 37, 95% CI: 0. 19-0. 71, P = 0. 003). The analysis indicates that elemene can enhance the chemotherapeutic effect on NSCLC, improve the quality of life, and reduce adverse effect of platinum-contained chemotherapeutics, thereby being worth promoting in clinic.

Gametophytic and zygotic selection leads to segregation distortion through in vivo induction of a maternal haploid in maize.

Production of maternal haploids via a male inducer can greatly accelerate maize breeding and is an interesting biological phenomenon in double fertilization. However, the mechanism behind haploid induction remains elusive. Segregation distortion, which is increasingly recognized as a potentially powerful evolutionary force, has recently been observed during maternal haploid induction in maize. The results present here showed that both male gametophytic and zygotic selection contributed to severe segregation distortion of a locus, named segregation distortion 1 (sed1), during maternal haploid induction in maize. Interestingly, analysis of reciprocal crosses showed that sed1 is expressed in the male gametophyte. A novel mapping strategy based on segregation distortion has been used to fine-map this locus. Strong selection for the presence of the sed1 haplotype from inducers in kernels with haploid formation and defects could be detected in the segregating population. Dual-pollination experiments showed that viable pollen grains from inducers had poor pollen competitive ability against pollen from normal genotypes. Although defective kernels and haploids have different phenotypes, they are most probably caused by the sed1 locus, and possible mechanisms for production of maternal haploids and the associated segregation distortion are discussed. This research also provides new insights into the process of double fertilization.

Morphological and molecular evidences for DNA introgression in haploid induction via a high oil inducer CAUHOI in maize.

The phenomenon of maternal haploid induction in maize was first described many years ago, but the underlying mechanism is still unclear. In this study, the Stock-6-derived, haploid-inducing line CAUHOI with high kernel oil content (KOC), was used as the pollinator to produce maternal haploids from the maize hybrid ZD958 with low KOC. CAUHOI is homozygous for the dominant marker gene R1-nj. Haploids were identified by morphological and cytological investigations. The frequency of haploid induction from this cross was 2.21%. Unexpectedly, many haploid kernels had weakly pigmented purple color on the embryo, and some haploid kernels had high KOC. Simple sequence repeat (SSR) analysis showed that 43.18% of the haploids carried segments from CAUHOI, and a small proportion (average 1.84%) of the genome of CAUHOI was introgressed into haploids. Haploid kernels with high KOC had a higher frequency of segment introgression from CAUHOI (2.92%) than that in haploid kernels with low KOC (1.79%), showing that the marker gene R1-nj and high-oil genes from CAUHOI were expressed during the development of some haploid embryos, and confirmed that the DNA introgression from the inducer parent occurred during maternal haploid induction. Together, these results suggested that the chromosome elimination was probably responsible for haploid induction in maize, and late somatic elimination might occur. Several possible mechanisms underlying haploid formation are discussed.

[Effect of Tangyikang in improving the function of pancreatic islet beta cells in patients with latent autoimmune diabetes mellitus in adults].

OBJECTIVE: To investigate the effect and mechanism of Tangyikang (TYK) for improving pancreatic islet beta cell function in patients with latent autoimmune diabetes mellitus in adults (LADA). METHODS: Seventy-four LADA patients were randomly assigned to two groups. The 37 patients in the treatment group were treated with TYK decoction (one dose consisted of red ginseng 10 g, milkvetch root 30 g, lilyturf root 15 g, wild weed 10 g, coptis root 15 g, cape-jasmine fruit 10 g, giant knotweed rhizome 10 g, safflower 10 g and moutan bark 10 g) combined with insulin therapy, and the 37 in the control group treated with insulin therapy alone, and the course for all was 3 months. Changes of glycosylated hemoglobin, index of pancreatic islet beta-cell function (delta CP(2h)/delta BS(2h)), serum interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) were observed before and after treatment. RESULTS: All the above-mentioned indexes were improved after treatment in both groups, the post-treatment data showed significant difference between groups in delta CP(2h)/delta BS(2h), (0.258 +/- 0.106 vs 0.168 +/- 0.054, higher in the treatment group, t = 4.626, P < 0.01), but with insignificant difference in glycosylated hemoglobin (t = 0.441, P = 0.660). Besides, the dosage of insulin used in the treatment group was less than that in the control group (t = -4.169, P < 0.01); covariance analysis showed, through excluding impact of different dosages insulin used, IL- 4 level was higher (F = 24.217, P < 0.01) and IFN-gamma level was lower (F = 14.198, P < 0.01) in the treatment group than those in the control group. CONCLUSIONS: TYK could improve the function of islet beta-cell, its possible mechanism is related with the regulation on cell immunity and the correction of T-lymphocyte subsets (Th1/Th2 ratio) imbalance.