Post-marketing safety concerns with elagolix: a disproportionality analysis of the FDA adverse event reporting system.

OBJECTIVE: Elagolix is approved for the treatment of moderate-to-severe pain associated with endometriosis. However, the long-term safety of elagolix in a large sample of real-world patients is unknown. METHODS: The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) reports were collected and analyzed from January 2019 to June 2023. Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms, were employed in data mining to quantify the signals of elagolix-related adverse events (AEs). RESULTS: After removing the non-drug-related AE signals, we detected several AE signals such as hot flushes, bone pain, suicidal ideation, depression, and increased liver enzymes, which were known during the clinical trial phase. In addition to this, we detected several unexpected important AEs that were not mentioned in the drug insert, including cystitis interstitial, parosmia, and epiploic appendagitis. The median onset time of elagolix-associated AEs was 28.5 days. CONCLUSION: Our study provides a comprehensive picture of the safety of elagolix in the post-marketing setting, while also identifying potential new AE signals. These findings emphasize the importance of continued monitoring of the potential risks of elagolix.

Disulfidptosis and ferroptosis related genes predict prognosis and personalize treatment for hepatocellular carcinoma.

Background: Understanding the interplay between disulfidptosis, ferroptosis, and hepatocellular carcinoma (HCC) could provide valuable insights into the pathogenesis of HCC and potentially identify novel therapeutic targets for the treatment of this deadly disease. This study aimed to identify a prognostic signature for HCC by examining the differential expression of genes related to disulfidptosis and ferroptosis (DRG-FRG), and to assess its clinical applicability. Methods: By integrating 23 disulfidptosis and 259 ferroptosis related genes with HCC messenger RNA (mRNA) expression data from The Cancer Genome Atlas (TCGA), differentially expressed DRG-FRG genes were identified. From these, 11 DRG-FRG genes were selected to construct a risk signature model using least absolute shrinkage and selection operator regression analyses. The prognostic performance of this model was evaluated by Kaplan-Meier survival analysis and time-dependent receiver operating characteristic (ROC) analysis. Subsequently, a nomogram was built by combining the signature with clinical variables. To further delve into the underlying mechanisms, we performed bioinformatics analysis using a variety of databases. Results: A prognostic signature based on 11 DRG-FRG genes effectively categorized HCC patients into high- and low-risk groups, showing a significant survival difference. Even after considering clinical variables, this signature remained an independent prognostic factor. Furthermore, the signature played a role in various critical biological processes and pathways that drive HCC progression. Potential therapeutic benefits could be derived from small molecule drugs targeting NQO1 and SLC7A11. Interestingly, the high-risk group exhibited resistance to several chemotherapeutic drugs, yet showed sensitivity to others when contrasted with the low-risk group. Lastly, the DRG-FRG genes signature had a strong correlation with the tumor immune microenvironment, marked by an elevated expression of immune checkpoint molecules in the high-risk group. Conclusions: The signature based on 11 DRG-FRG genes stands out as a promising prognostic biomarker for HCC. Beyond its predictive value, it sheds light on the intricate crosstalk between DRG-FRG genes and HCC. Importantly, these findings could pave the way for enhanced prognostic prediction, informed treatment decisions, and the advancement of immunotherapy for HCC patients.

Structural and compositional diversity of biosurfactants produced by a novel strain of Sporosarcina luteola ME44 from oil reservoir.

The urealytically active microorganism Sporosarcina luteola induces the precipitation of metals, which has attracted attention in biomineralization, bioremediation, and industrial waste recycling. Herein, we report a novel biosurfactant-producing strain of S. luteola ME44 isolated from Chinese Oilfield. The structure, composition, and surface activity of the biosurfactants produced by S. luteola ME44 were investigated by using a combination of the high-performance liquid chromatography, time-of-flight mass spectrometry, and surface tensiometer. The biosurfactant extracted by strain ME44 was identified as surfactin with five variants and the yield was 1010 ± 60 mg⋅L-1 . This is the first report on the structural composition and surface activity of biosurfactants isolated from the S. luteola. It extended our knowledge about the role of the species S. luteola in the ecosystem of extreme natural environments such as oil reservoir. In addition, S. luteola ME44 showed bioprecipitation properties for metal ions Cd(II), Cu(II), Zn(II), and Ag(I), which indicated the application potential of S. luteola in the field of bioremediation.

Retinal safety and toxicity study of artesunate in vitro and in vivo.

Background: Artesunate (ART), a member of the artemisinin family, possesses multi-properties, including anti-inflammation, anti-oxidation, and anti-tumor. ART was recently reported to show anti-neovascularization effect on the cornea, iris, and retina. Compared to the expensive anti-VEGF treatment, this versatile, economical treatment option is attractive in the ophthalmic field. The safety and toxicity profile of ART intravitreal application are in utmost need. Methods: In this study, immortalized microglial (IMG) cells were treated with ART to determine the safe concentrations without inducing overt inflammatory reactions. Reverse transcription-polymerase chain reaction analysis was used to detect the cytokine expressions in IMG cells in response to ART stimulation. Various doses of ART were intravitreally injected into the right eyes of C57BL/6 mice. Retinal function was tested by electroretinogram, and retinal ganglion cell (RGC) survival was evaluated by counting Brn3a stained cells in flat-mounted retinas at 7 days after ART injection. Results: ART below 5µM was safe for IMG cells in vitro. Both 2.5 and 5 â€‹µM ART treatment increased IL-10 gene expression in IMG cells while not changing IL-1ß, IL-6, TNF-α, and Arg-1. In the in vivo study, intravitreal injection of ART below 100 â€‹µM did not cause deterioration in the retinal function and RGC survival of the mouse eyes, while 1 â€‹mM ART treatment significantly attenuated both the scotopic and photopic b-wave amplitudes and impaired RGC survival. In addition, treatment with ART of 25, 50, and 100 â€‹µM significantly decreased TNF-α gene expression while ART of 100 â€‹µM significantly increased IL-10 in the mouse retina. Conclusions: Intravitreal injection of 100 â€‹µM ART could downregulate TNF-α while upregulate IL-10 in the mouse retina without causing retinal functional deterioration and RGC loss. ART might be used as anti-inflammatory agent for retinal disorders.

The polarization of M2 macrophages can be adjusted to alleviate renal injury by methylprednisolone in sepsis-AKI.

Acute kidney injury in sepsis patients has an extreme mortality rate in clinical. It obviously seems that immune cells, for example, macrophages are involved with this process. Macrophages, as highly important immune cells, play a significant role in the development of human kidney diseases. But the specific role of macrophages in this process is still unclear. Under different timeline points, we surprisingly found that macrophages had the most dynamic changes in acute kidney injury immune cells. Based on macrophages' functions, they are primarily classified into M1 macrophages (pro-inflammatory) and M2 macrophages (anti-inflammatory). The polarization of M2 macrophages is closely associated with the seriousness of sepsis-induced kidney injury, but how to modulate their polarization to alleviate sepsis-associated renal damage remains unknown. We discovered that the polarization of M2 macrophages after methylprednisolone injection can significantly alleviate acute kidney injury by reducing secreted cytokine. This study suggests that the proportion of macrophage subtypes can be regulated by methylprednisolone to alleviate acute kidney injury in sepsis to provide a new sight for a clinical to provide a promising strategy for renal injury caused.

A new biosurfactant-producing strain, Fictibacillus nanhaiensis ME46, isolated from an oil field in China.

The genus Fictibacillus contains twelve species significant in the synthesis of cellulose-degrading enzymes and phenylalanine dehydrogenase, isolated mainly from marine sedimentary environments. Here, we report a new biosurfactant-producing strain, Fictibacillus nanhaiensis ME46, isolated from Daqing oil field in China. The biosurfactant extracted from Strain ME46 was determined as surfactin, one of the representative families of lipopeptide biosurfactants. The yield of the surfactin produced by strain ME46 was 0.62 g·L-1 as determined by high-performance liquid chromatography, and the critical micelle concentration (CMC) of the surfactin was estimated to be about 68 mg·L-1 and the surface tension at CMC was 35.1 mN·m-1. This study extended our knowledge about the role of the species Fictibacillus nanhaiensis in the ecosystem of natural environments such as the oil field.

Neuroprotection of Emodin by Inhibition of Microglial NLRP3 Inflammasome-Mediated Pyroptosis.

BACKGROUND: Neuroinflammation triggered by chronic cerebral ischemia-induced microglial pyroptosis is a significant contributor to vascular cognitive impairment. It has been shown that emodin possesses anti-inflammatory and neuroprotective properties, however, it's potential molecular and signaling transduction pathway remains to be illuminated. This study researched the neuroprotective mechanisms of emodin focussing on emodin effects on lipopolysaccharide/adenosine triphosphate (LPS/ATP)-caused pyroptosis in BV2 cells and HT-22 hippocampal neurons. METHODS: To explore the neuroprotective effect of emodin, Emodin was applied to BV2 cells, HT-22 hippocampal neurons, and BV2/HT-22 co-cultures stimulated with LPS/ATP to evaluate the cell morphology, levels of inflammatory factors, NLRP3 inflammatory inflammasome activity and focal pyroptosis-related protein expression, as same as neuronal apoptosis. RESULTS: Emodin alleviated LPS/ATP-induced pyroptosis of BV2 cells by preventing the activity of the NLRP3 inflammasome and the cleavage of pyroptosis executive protein Gasdermin D (GSDMD). Furthermore, levels of interleukin (IL)-18, IL-1ß and tumor necrosis factor (TNF)-α were reduced, the apoptosis of HT-22 hippocampal neurons was attenuated, and cell viability was restored. CONCLUSIONS: Emodin can antagonize microglial neurotoxicity by inhibiting microglial pyroptosis, thereby exerting anti-inflammatory and neuroprotective effects.

[Effects of Nardostachys jatamansi on gut microbiota of rats with Parkinson's disease].

Under the guidance of the traditional Chinese medicine(TCM) theory of "Zangfu-organs of spleen and stomach" and the modern theory of "microbiota-gut-brain axis", this study explored the effects of Nardostachys jatamansi on the gut microbiota of rats with Parkinson's disease(PD). The 40 SD rats were randomly divided into the control group, PD model group, levodopa group, and Nardostachys jatamansi ethanol extract group. The PD model was established by subcutaneous injection of rotenone in the neck and back area. After 14 days of intragastric administration, the PD rats' behaviors were analyzed through open field test, inclined plane test, and pole test. After the behavioral tests, the striatum, colon, and colon contents of rats in each group were collected. Western blot was employed to detect the protein expression of tyrosine hydroxylase(TH) and α-synuclein(α-syn) in striatum and that of α-syn in colon. Enzyme linked immunosorbent assay(ELISA) was used to detect the levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), and nuclear factor-kappa B(NF-κB) in striatum and colon. High-throughput sequencing of 16 S rRNA gene was conducted to detect the differences in microbial diversity, abundance, differential phyla, and dominant bacteria of rats between groups. The results indicated that Nar. ethanol extract could relieve dyskinesia, reverse the increased levels of α-syn, TNF-α, IL-1ß, and NF-κB in striatum, and improve the protein expression of TH in striatum of PD rats. The α diversity analysis indicated a significant decrease in diversity and abundance of gut microbiota in the PD model. The results of linear discriminant analysis effect size(LEfSe) of dominant bacteria indicated that Nardostachys jatamansi ethanol extract increased the relative abundance of Clotridiaceae, Lachnospiraceae, and Anaerostipes, and reversed the increased relative abundance of Proteobacteria, Gammaproteobacteria, Enterobacteriaceae, and Escherichia-Shigella in PD model group to exhibit the neuroprotective effect. In summary, the results indicated that Nar. ethanol extract exert the therapeutic effect on PD rats. Specifically, the extract may regulate gut microbiota, decrease the levels of proinflammatory cytokines, and reduce the protein aggregation of α-syn in the colon and striatum to alleviate intestinal inflammation and neuroinflammation. This study provides a basis for combining the theory of "Zangfu-organs of spleen and stomach" with the theory of "microbiota-gut-brain axis" to treat PD.

The mitochondrial ß-oxidation enzyme HADHA restrains hepatic glucagon response by promoting ß-hydroxybutyrate production.

Disordered hepatic glucagon response contributes to hyperglycemia in diabetes. The regulators involved in glucagon response are less understood. This work aims to investigate the roles of mitochondrial ß-oxidation enzyme HADHA and its downstream ketone bodies in hepatic glucagon response. Here we show that glucagon challenge impairs expression of HADHA. Liver-specific HADHA overexpression reversed hepatic gluconeogenesis in mice, while HADHA knockdown augmented glucagon response. Stable isotope tracing shows that HADHA promotes ketone body production via ß-oxidation. The ketone body ß-hydroxybutyrate (BHB) but not acetoacetate suppresses gluconeogenesis by selectively inhibiting HDAC7 activity via interaction with Glu543 site to facilitate FOXO1 nuclear exclusion. In HFD-fed mice, HADHA overexpression improved metabolic disorders, and these effects are abrogated by knockdown of BHB-producing enzyme. In conclusion, BHB is responsible for the inhibitory effect of HADHA on hepatic glucagon response, suggesting that HADHA activation or BHB elevation by pharmacological intervention hold promise in treating diabetes.

Lycium barbarum extract promotes M2 polarization and reduces oligomeric amyloid-ß-induced inflammatory reactions in microglial cells.

Lycium barbarum (LB) is a traditional Chinese medicine that has been demonstrated to exhibit a wide variety of biological functions, such as antioxidation, neuroprotection, and immune modulation. One of the main mechanisms of Alzheimer's disease is that microglia activated by amyloid beta (Aß) transform from the resting state to an M1 state and release pro-inflammatory cytokines to the surrounding environment. In the present study, immortalized microglial cells were pretreated with L. barbarum extract for 1 hour and then treated with oligomeric Aß for 23 hours. The results showed that LB extract significantly increased the survival of oligomeric Aß-induced microglial cells, downregulated the expression of M1 pro-inflammatory markers (inducible nitric oxide synthase, tumor necrosis factor α, interleukin-6, and interleukin-1ß), and upregulated the expression of M2 anti-inflammatory markers (arginase-1, chitinase-like protein 3, and interleukin-4). LB extract also inhibited the oligomeric Aß-induced secretion of tumor necrosis factor α, interleukin-6, and interleukin-1ß in microglial cells. The results of in vitro cytological experiments suggest that, in microglial cells, LB extract can inhibit oligomeric Aß-induced M1 polarization and concomitant inflammatory reactions, and promote M2 polarization.

Septoplasty alone is not suitable for most structural nasal obstructions.

Septoplasty is widely used in the treatment of structural nasal obstructions, and it also has a good effect and a high degree of postoperative satisfaction. However, there a large number of structures demonstrate abnormalities related to structural nasal obstruction, including the external nose, maxilla, nasal cavity and paranasal sinus. Nasal septum deviation is only one signs of structural nasal obstruction and does not represent all possible structural abnormalities of the nasal cavity and its surrounding structure. Septoplasty is only performed to correct deviations of the nasal septum, which in many cases is obviously insufficient in restoring the symmetry of the nasal structure. Therefore, septoplasty alone is not suitable for the treatment of most structural nasal obstructions. Nasal ventilation expansion surgery, which typically covers more abnormal structural correction procedures than septoplasty, should be used when describing the treatment of structural nasal obstruction.

Chinese Association for the Study of Pain: Expert consensus on chronic postsurgical pain.

Chronic postsurgical pain is a common surgical complication that severely reduces a patient's quality of life. Many perioperative interventions and management strategies have been developed for reducing and managing chronic postsurgical pain. Under the leadership of the Chinese Association for the Study of Pain, an editorial committee was formed for chronic postsurgical pain diagnosis and treatment by experts in relevant fields. The editorial committee composed the main content and framework of this consensus and established a working group. The working group conducted literature review (1989-2020) using key words such as "surgery", "post-surgical", "post-operative", "pain", "chronic", and "persistent" in different databases including MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews. Only publications in the English language were included. The types of literature included systematic reviews, randomized controlled studies, cohort studies and case reports. This consensus was written based on clinical practice combined with literature evidence. The first draft of the consensus was rigorously reviewed and edited by all the editorial committee experts before being finalized. The level of evidence was assessed by methodological experts based on the Oxford Centre for Evidence-Based Medicine Levels of Evidence. The strength of recommendation was evaluated by all editorial committee experts, and the opinions of most experts were adopted as the final decision. The recommendation level "strong" generally refers to recommendations based on high-level evidence and consistency between clinical behavior and expected results. The recommendation level "weak" generally refers to the uncertainty between clinical behavior and expected results based on low-level evidence.

New evidence for a hydroxylation pathway for anaerobic alkane degradation supported by analyses of functional genes and signature metabolites in oil reservoirs.

Microbial degradation of recalcitrant alkanes under anaerobic conditions results in the accumulation of heavy oil fraction in oil reservoirs. Hydroxylation of alkanes is an important activation mechanism under anaerobic conditions, but the diversity and distribution of the responsible microorganisms in the subsurface environment are still unclear. The lack of functional gene polymerase chain reaction (PCR) primers and commercially available intermediate degradation chemical compounds are the major obstacles for this research. In this investigation, PCR primers for the ahyA gene (encoding alkane hydroxylase) were designed, evaluated, and improved based on the nucleotide sequences available. Using microbial genomic DNA extracted from oil-contaminated soil and production water samples of oil reservoirs, ahyA gene nucleotide sequences were amplified and retrieved successfully from production water sample Z3-25 of Shengli oilfield. Additionally, the signature biomarker of 2-acetylalkanoic acid was detected in both Shengli and Jiangsu oilfields. These results demonstrate that anaerobic hydroxylation is an active mechanism used by microorganisms to degrade alkanes in oxygen-depleted oil reservoirs. This finding expands the current knowledge of biochemical reactions about alkane degradation in subsurface ecosystems. In addition, the PCR primers designed and tested in this study serve as an effective molecular tool for detecting the microorganisms responsible for anaerobic hydroxylation of alkanes in this and other ecosystems.

Corosolic acid inhibits colorectal cancer cells growth as a novel HER2/HER3 heterodimerization inhibitor.

BACKGROUND AND PURPOSE: Colorectal cancer is the third most common cancer worldwide. HER2 and HER3 are two members of human epidermal receptor family of tyrosine kinase receptors (RTKs) and associated with poor survival in colorectal cancer. They have been observed as important therapeutic targets in various types of cancer. Corosolic acid, a natural pentacyclic triterpene, has been demonstrated to have a significant anti-cancer activity. However, the target of corosolic acid has not yet been explored. This study aimed to reveal the direct targets of corosolic acid underlying its anti-cancer activities. EXPERIMENTAL APPROACH: The targets of corosolic acid were revealed by the phospho-RTK array, bio-layer interferometry, co-immunoprecipitation, and proximity ligation assay. The inhibitory action of corosolic acid on HER2/HER3 heterodimerization and related downstream signalling were investigated in HCT116 and SW480 cells. In addition, the chemo-preventive effects of corosolic acid were validated in both HCT116 xenograft model and AOM/DSS model. KEY RESULTS: Our results demonstrated that corosolic acid could prevent NRG1-induced HER2/HER3 heterodimerization and suppress the phosphorylation of both HER2 and HER3. Furthermore, HER2 and HER3 could regulate the downstream signalling pathways of RalA/RalBP1/CDK1 and PI3K/Akt/PKA, respectively, resulting in the changes in phosphorylation of Drp1 and mitochondrial dynamics. corosolic acid exhibited anti-cancer activity in both HCT116 xenograft model and AOM/DSS model. CONCLUSIONS AND IMPLICATIONS: Collectively, our results demonstrated corosolic acid directly targeted HER2 and HER3 heterodimerization and inhibited mitochondrial fission via regulating RalA/RalBP1/CDK1 and PI3K/Akt/PKA pathways, revealing a novel mechanism underlying the beneficial effects of corosolic acid on colorectal cancer.

The optimization of heterogeneous catalytic conditions in the direct alkylation of waste vegetable oil.

Alkylated waste vegetable oil is a versatile intermediate product in the synthesis of bio-based materials. Heterogeneous catalytic condition with high conversion rate in the direct alkylation of waste vegetable oil was reported and the deactivation mechanism of catalyst was revealed. The total exchange capacity, elemental composition and pyrolysis product of catalyst before and after the alkylation reaction were analysed by back titration, elemental analysis, electrospray ionization mass spectrometry, gas chromatography mass spectrometry and pyrolysis-gas chromatography/mass spectrometry, respectively. The results indicated that the metallic and non-metallic (C, H) elements contents of the catalyst have very much increased with great changes in pyrolysis product and a slight decrease in the total exchange capacity. The formation of insoluble polymers through Diels-Alder cycloaddition between triglycerides was proved to be the major factor causing the dysfunction of the catalytic centre. The metal ions from corrosion of the reactor were the minor factor causing about 2.56% loss of the catalytic centre. Moreover, the catalyst was able to maintain high catalytic efficiency when replacing the raw materials with other waste vegetable oil having low concentration of polyunsaturated fatty acids, which is significant for producing not only the aryl fatty acids derivatives but also the bio-based surfactants.

Simultaneous detection of transcribed functional assA gene and the corresponding metabolites of linear alkanes (C4, C5, and C7) in production water of a low-temperature oil reservoir.

Methanogenic hydrocarbon degradation is an important biogeochemical process in oil reservoirs; however, genomic DNA-based analysis of microorganisms and metabolite detection are not conclusive for identification of the ongoing nature of this bioprocess. In this study, a suite of analyses, involving the study of microbial community and selective gene quantification of both genomic DNA and RNA together with signature metabolites, were performed to comprehensively advance the understanding of the methanogenic biodegradation of hydrocarbons in a low-temperature oilfield. The fumarate addition products for alkanes-C4, C5, and C7-alkylsuccinates-and transcribed assA and mcrA genes were simultaneously detected in the production water sample, providing robust and convincing evidence for both the initial activation of n-alkanes and methane metabolism in this oilfield. The clone library of assA gene transcripts showed that Smithella was active and most likely responsible for the addition of fumarate to n-alkanes, whereas Methanoculleus and Methanothrix were the dominant and active methane-producers via CO2 reduction and acetoclastic pathways, respectively. Additionally, qPCR results of assA and mcrA genes and their transcribed gene copy numbers revealed a roughly similar transcriptional activity in both n-alkanes-degraders and methane producers, implying that they were the major participants in the methanogenic degradation of n-alkanes in this oilfield. To the best of our knowledge, this is the first report presenting sufficient speculation, through detection of signature intermediates, corresponding gene quantification at transcriptional levels, and microbial community analysis, of methanogenic degradation of n-alkanes in production water of an oil reservoir.

Long-chain n-alkane biodegradation coupling to methane production in an enriched culture from production water of a high-temperature oil reservoir.

Paraffinic n-alkanes (C22-C30), crucial portions of residual oil, are generally considered to be difficult to be biodegraded owing to their general solidity at ambient temperatures and low water solubility, rendering relatively little known about metabolic processes in different methanogenic hydrocarbon-contaminated environments. Here, we established a methanogenic C22-C30 n-alkane-degrading enrichment culture derived from a high-temperature oil reservoir production water. During two-year incubation (736 days), unexpectedly significant methane production was observed. The measured maximum methane yield rate (164.40 µmol L-1 d-1) occurred during the incubation period from day 351 to 513. The nearly complete consumption (> 97%) of paraffinic n-alkanes and the detection of dicarboxylic acids in n-alkane-amended cultures indicated the biotransformation of paraffin to methane under anoxic condition. 16S rRNA gene analysis suggested that the dominant methanogen in n-alkane-degrading cultures shifted from Methanothermobacter on day 322 to Thermoplasmatales on day 736. Bacterial community analysis based on high-throughput sequencing revealed that members of Proteobacteria and Firmicutes exhibiting predominant in control cultures, while microorganisms affiliated with Actinobacteria turned into the most dominant phylum in n-alkane-dependent cultures. Additionally, the relative abundance of mcrA gene based on genomic DNA significantly increased over the incubation time, suggesting an important role of methanogens in these consortia. This work extends our understanding of methanogenic paraffinic n-alkanes conversion and has biotechnological implications for microbial enhanced recovery of residual hydrocarbons and effective bioremediation of hydrocarbon-containing biospheres.

Osimertinib or EGFR-TKIs/chemotherapy in patients with EGFR-mutated advanced nonsmall cell lung cancer: A meta-analysis.

BACKGROUND: The aim of this meta-analysis is to investigate the impact of Osimertinib on treatment efficacy in advanced nonsmall cell lung cancer (NSCLC). METHODS: Trials comparing Osimertinib against epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)/chemotherapy in patients with NSCLC with an epidermal growth factor receptor (EGFR) mutation were included, and the pooled data for progression-free survival (PFS), overall survival (OS), overall response rate (ORR), disease control rate (DCR), and adverse events (AEs) were analyzed. RESULTS: Analysis results based on 6 eligible trials showed that Osimertinib significantly improved the overall PFS (hazard ratio [HR] = 0.38, 95% confidence interval [CI] = 0.29-0.50), improved the OS (HR = 0.66, 95% CI = 0.48-0.89), increased the ORR (odds ratio [OR] = 1.76, 95% CI = 1.14-2.72), increased the overall DCR (OR = 1.18, 95% CI = 1.02-1.37), and reduced the grade 3 or greater AEs (relative ratio [RR] = 0.50, 95% CI = 0.33-0.75) in all subgroups except in the ORR in the Exon 19 deletion (Ex19del) and/or L858R subgroup. Compared to patients with Ex19del and/or L858R mutation, patients with the T790M mutation had the benefits of a greater PFS (41.7%), a greater ORR (80.0%), a greater DCR (71.2%), and fewer grade 3 or greater AEs (70.7%) (each P < .05). Race, sex, age, EGFR mutation, and smoking history may significantly predict additional benefits from Osimertinib, but there were no significant differences between subgroups stratified by these clinical characteristics. CONCLUSIONS: Osimertinib showed greater treatment benefit for patients with NSCLC with EGFR mutation than EGFR-TKIs/chemotherapy, especially for T790M mutation-positive patients.

Longevity-Associated Forkhead Box O3 (FOXO3) Single Nucleotide Polymorphisms are Associated with Type 2 Diabetes Mellitus in Chinese Elderly Women.

BACKGROUND This study aimed to investigate the association of single nucleotide polymorphisms (SNPs) of Forkhead box O3 (FOXO3) gene with type 2 diabetes mellitus (T2D). MATERIAL AND METHODS A total of 843 elderly residents from east China were enrolled in this study, which included 426 patients with type 2 diabetes and 417 controls. Four SNPs were analyzed by qPCR. Genotype frequencies of the 4 SNPs in FOXO3 of the patients and controls were analyzed using logistic regression analysis. The association between each SNP and clinical indicators was analyzed by linear regression analysis. RESULTS None of the 4 FOXO3 variants, rs13217795, rs2764264, rs2802292, and rs13220810, were associated with the risk of type 2 diabetes compared to controls. However, rs13217795, rs2764264, and rs2802292 were associated with lower blood glucose levels. Notably, further subgroup analysis indicated that the longevity-associated alleles of FOXO3 SNP (rs13217795, rs2764264, and rs2802292) were associated with lower blood glucose levels in women (TC versus TT, -0.724 mmol/L, P=0.005; CC versus TT, -1.093 mmol/L, P=0.03; TC versus TT, -0.801 mmol/L, P=0.002; CC versus TT, -1.212 mmol/L, P=0.001; TG versus TT, -0.754 mmol/L, P=0.004; and GG versus TT, -1.150 mmol/L, P=0.001) but not in men. CONCLUSIONS The results indicated that longevity-associated FOXO3 variants were correlated with lower blood glucose levels in elderly women with type 2 diabetes in east China.

Inhibition of KiSS-1 on metastasis of nasopharyngeal carcinoma implant tumor in nude mice.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a kind of head-neck malignant neoplasm originated from the nasopharyngeal epithelium and is mainly prevalent in Southern China and Southeast Asia countries. KiSS-1 is an inhibitor of tumor metastasis in a range of cancers. METHODS: We establish a cell substrain of SUNE-1-5-8F (NPC cell line from humans) that trsnfected with lentiviral vectors carried with KiSS-1 gene and were selected by puromycin. A transplantation tumor animal model in BALB/c-nu mice was successfully established with a substrain that stably overexpressed KiSS-1. RESULTS: Our result showed that the size of transplantation tumor in the nude mice with KiSS-1 overexpression in transplantation tumor was not difference from the size of transplantation tumor in the controlled transplantation tumor mice. We detected metastatic tumor in lung but not in liver. Moreover, we also found that in the nude mice with KiSS-1 overexpression in transplantation tumor showed extremely fewer metastatic tumor in lung compared with the controlled transplantation tumor mice model. In conclusion, KiSS-1 may be beneficial for the inhibition of metastasis of human NPC. CONCLUSION: This study may throw light on the treatment of NPC and may help improve the prognosis of patients with NPC.