Mangiferin improves early porcine embryonic development by reducing oxidative stress.

Mangiferin (MGN) is primarily found in the fruits, leaves, and bark of plants of the Anacardiaceae family, including mangoes. MGN exhibits various pharmacological effects, such as protection of the liver and gallbladder, anti-lipid peroxidation, and cancer prevention. This study aimed to investigate the effects of MGN supplementation during in vitro culture (IVC) on the antioxidant capacity of early porcine embryos and the underlying mechanisms involved. Porcine parthenotes in the IVC medium were exposed to different concentrations of MGN (0, 0.01, 0.1, and 1 µM). The addition of 0.1 µM MGN significantly increased the blastocyst formation rate of porcine embryos while reducing the apoptotic index and autophagy. Furthermore, the expression of antioxidation-related (SOD2, GPX1, NRF2, UCHL1), cell pluripotency (SOX2, NANOG), and mitochondria-related (TFAM, PGC1α) genes was upregulated. In contrast, the expression of apoptosis-related (CAS3, BAX) and autophagy-related (LC3B, ATG5) genes decreased after MGN supplementation. These findings suggest that MGN improves early porcine embryonic development by reducing oxidative stress-related genes.

Prevalence of cigarette use and addiction among Chinese females by age and province: Findings from nationwide China Health Literacy Survey during 2018-19.

BACKGROUND: The prevalence of cigarette smoking among women is significantly different from that of men, however, cigarette use by women is little known. The study aims to describe cigarette use prevalence and patterns among Chinese females by age and province. METHODS: This study was based on the 2018 China Health Literacy Survey (2018 CHLS), a nationally representative cross-sectional study, and our analysis included 43,319 female participants aged 20-69 with valid data. The prevalence of cigarette use was estimated overall by sociodemographic factors and weighted based on the census population data. The logistic regression model was conducted to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the risk factors associated with cigarette use and dependency. RESULTS: In China, the estimated female current cigarette use prevalence was 1.85%, with over half of the population suffering from tobacco dependence (7.34 million). Jilin Province has the highest cigarette prevalence among women (10.59%), while Fujian Province has the lowest (0.27%). Participants over 60 years old (aOR=1.61, 95%CI=1.20-2.14), single (aOR=1.54, 95%CI=1.07-2.21), with primary education (aOR=1.93, 95%CI=1.47-2.52) were more likely to smoke. The age of smoking initiation among women intergenerational advanced, and compared to the cigarette users without tobacco dependence, those who have tobacco dependence start smoking earlier in all age groups (25.69 years vs. 19.36 years, p<0.001). CONCLUSIONS: The cigarette use prevalence among Chinese women was 1.85%, and there are significant differences among provinces. We noted a trend of women initiating smoking at increasingly younger ages, particularly among those with tobacco dependence.

Apigenin delays postovulatory oocyte aging by reducing oxidative stress through SIRT1 upregulation.

After ovulation, senescent oocytes inevitably experience reduced quality and defects in embryonic development. Apigenin (API) is a flavonoid with a wide range of pharmacological effects. Therefore, this study examined the protective effects of API on the quality of porcine oocytes during in-vitro ageing and the underlying mechanisms. The results showed that API treatment could reduce the activation rate after aging for 48 h. In addition, API significantly reduced reactive oxygen species, abnormal distribution of mitochondria, early apoptosis in ageing oocytes, increased glutathione, and mitochondrial adenosine triphosphate levels in ageing oocytes. Importantly, API increased the embryonic development rate in aged oocytes. We also examined molecular changes, finding decreased sirtuin 1 expression in in-vitro postovulatory oocytes, but API reversed this effect. Our results suggest that API attenuates the deterioration of oocyte quality during in-vitro ageing, possibly by reducing oxidative stress through the upregulation of sirtuin 1.

Identification and Validation of a Novel Anoikis-Related Gene Signature for Predicting Survival in Patients With Serous Ovarian Cancer.

Background: Ovarian cancer is an extremely deadly gynecological malignancy, with a 5-year survival rate below 30%. Among the different histological subtypes, serous ovarian cancer (SOC) is the most common. Anoikis significantly contributes to the progression of ovarian cancer. Therefore, identifying an anoikis-related signature that can serve as potential prognostic predictors for SOC is of great significance. Methods: We intersected 308 anoikis-related genes (ARGs) and identified those significantly associated with SOC prognosis using univariate Cox regression. A LASSO Cox regression model was constructed and evaluated using Kaplan-Meier and receiver operating characteristic (ROC) analyses in TCGA (The Cancer Genome Atlas) and GSE26193 cohorts. We conducted quantitative real-time polymerase chain reaction (qPCR) to assess mRNA levels and applied bioinformatics to investigate the correlation between risk groups and gene expression, mutations, pathways, tumor immune microenvironment (TIME), and drug sensitivity in SOC. Results: Among 308 ARGs, 28 were significantly associated with SOC prognosis. A 13-gene prognostic model was established through LASSO Cox regression in TCGA cohort. High-risk group had poorer prognosis than low-risk group (median overall survival (mOS): 34.2 vs. 57.1 months, hazard ratio (HR): 2.590, 95% confidence interval (CI): 0.159 - 6.00, P < 0.001). The area under the curve (AUC) values of 0.63, 0.65, and 0.74 reflected the predictive performance for 3-, 5-, and 8-year overall survival (OS) in GSE26193 validation cohort. Functional enrichment, pathway analysis, and TIME analysis identified distinct characteristics between risk groups. Drug sensitivity analysis revealed potential drug advantages for each group. Furthermore, qPCR validation once again confirmed the effectiveness of the risk model in SOC patients. Conclusions: We developed and validated a robust ARG model, which could be used to predict OS in SOC patients. By systematically analyzing the correlation between the risk score of the ARGs signature model and various patterns, including the TIME and drug sensitivity, our findings suggest that this prognostic model contributes to the advancement of personalized and precise therapeutic strategies. Nevertheless, further validation studies and investigations into the underlying mechanisms are warranted.

Improving the developmental competences of porcine parthenogenetic embryos by Notoginsenoside R1-induced enhancement of mitochondrial activity and alleviation of proapoptotic events.

Notoginsenoside R1 (NGR1), derived from the Panax notoginseng root and rhizome, exhibits diverse pharmacological influences on the brain, neurons, and osteoblasts, such as antioxidant effects, mitochondrial function protection, energy metabolism regulation, and inhibition of oxygen radicals, apoptosis, and cellular autophagy. However, its effect on early porcine embryonic development remains unclear. Therefore, we investigated NGR1's effects on blastocyst quality, reactive oxygen species (ROS) levels, glutathione (GSH) levels, mitochondrial function, and embryonic development-related gene expression in porcine embryos by introducing NGR1 during the in vitro culture (IVC) of early porcine embryos. Our results indicate that an addition of 1 µM NGR1 significantly increased glutathione (GSH) levels, blastocyst formation rate, and total cell number and proliferation capacity; decreased ROS levels and apoptosis rates in orphan-activated porcine embryos; and improved intracellular mitochondrial distribution, enhanced membrane potential, and reduced autophagy. In addition, pluripotency-related factor levels were elevated (NANOG and octamer-binding transcription factor 4 [OCT4]), antioxidant-related genes were upregulated (nuclear factor-erythroid 2-related factor 2 [NRF2]), and apoptosis- (caspase 3 [CAS3]) and autophagy-related genes (light chain 3 [LC3B]) were downregulated. These results indicate that NGR1 can enhance early porcine embryonic development by protecting mitochondrial function.

Customized liver organoids as an advanced in vitro modeling and drug discovery platform for non-alcoholic fatty liver diseases.

Non-alcoholic fatty liver disease (NAFLD) and its progressive form non-alcoholic steatohepatitis (NASH) have presented a major and common health concern worldwide due to their increasing prevalence and progressive development of severe pathological conditions such as cirrhosis and liver cancer. Although a large number of drug candidates for the treatment of NASH have entered clinical trial testing, all have not been released to market due to their limited efficacy, and there remains no approved treatment for NASH available to this day. Recently, organoid technology that produces 3D multicellular aggregates with a liver tissue-like cytoarchitecture and improved functionality has been suggested as a novel platform for modeling the human-specific complex pathophysiology of NAFLD and NASH. In this review, we describe the cellular crosstalk between each cellular compartment in the liver during the pathogenesis of NAFLD and NASH. We also summarize the current state of liver organoid technology, describing the cellular diversity that could be recapitulated in liver organoids and proposing a future direction for liver organoid technology as an in vitro platform for disease modeling and drug discovery for NAFLD and NASH.

Protective effect of onion peel extract on ageing mouse oocytes.

Mammalian oocytes not fertilized immediately after ovulation can undergo ageing and a rapid decline in quality. The addition of antioxidants can be an efficient approach to delaying the oocyte ageing process. Onion peel extract (OPE) contains quercetin and other flavonoids with natural antioxidant activities. In this study, we investigated the effect of OPE on mouse oocyte ageing and its mechanism of action. The oocytes were aged in vitro in M16 medium for 16 h after adding OPE at different concentrations (0, 50, 100, 200, and 500 µg/ml). The addition of 100 µg/ml OPE reduced the oocyte fragmentation rate, decreased the reactive oxygen species (ROS) level, increased the glutathione (GSH) level, and improved the mitochondrial membrane potential compared with the control group. The addition of OPE also increased the expression of SOD1, CAT, and GPX3 genes, and the caspase-3 activity in OPE-treated aged oocytes was significantly lower than that in untreated aged oocytes and similar to that in fresh oocytes. These results indicated that OPE delayed mouse oocyte ageing by reducing oxidative stress and apoptosis and enhancing mitochondrial function.

Chrysoeriol Improves In Vitro Porcine Embryo Development by Reducing Oxidative Stress and Autophagy.

Chrysoeriol (CHE) is a flavonoid substance that exists in many plants. It has various physiological and pharmacological effects, including anti-inflammatory, antioxidant, anti-tumor, and protective activity, especially for the cardiovascular system and liver. Among common livestock embryos, porcine embryos are often considered high-quality objects for studying the antioxidant mechanisms of oocytes. Because porcine embryos contain high levels of lipids, they are more vulnerable to external stimuli, which affect development. Our study explored the influence of CHE supplementation on oxidative stress in porcine oocytes and its possible mechanisms. Different concentrations of CHE (0, 0.1, 1, and 3 µM) were supplemented in the in vitro culture medium of the porcine oocytes. The results showed that supplementation with 1 µM CHE significantly increased the blastocyst rate and total cell number of embryos in vitro. After finding the beneficial effects of CHE, we measured reactive oxygen species (ROS), glutathione (GSH), and mitochondrial membrane potential (MMP) when the oocytes reached the 4-cell stage of development and determined the levels of apoptosis, cell proliferation, and autophagy at the blastocyst stage of development. The expression levels of some related genes were preliminarily detected by qRT-PCR. The results showed that the apoptosis of blastocysts in the CHE-treated culture also decreased compared with the untreated culture. Furthermore, CHE downregulated intracellular ROS and increased GSH in the embryos. CHE was also shown to improve the activity of mitochondria and inhibit the occurrence of autophagy. In addition, antioxidant-related genes (SOD1, SOD2, and CAT) and cell pluripotency-related genes (SOX2, OCT4, and NANOG) were upregulated. At the same time, apoptosis-related (Caspase 3) and autophagy-related (LC3B) genes showed a downward trend after supplementation with CHE. These results indicate that CHE improved the development of porcine embryos in vitro by reducing oxidative stress and autophagy levels.

Dihydromyricetin supplementation during in vitro culture improves porcine oocyte developmental competence by regulating oxidative stress.

Dihydromyricetin (DHM), a dihydroflavonoid compound, exhibits a variety of biological activities, including antitumor activity. However, the effects of DHM on mammalian reproductive processes, especially during early embryonic development, remain unclear. In this study, we added DHM to porcine zygotic medium to explore the influence and underlying mechanisms of DHM on the developmental competence of parthenogenetically activated porcine embryos. Supplementation with 5 µM DHM during in vitro culture (IVC) significantly improved blastocyst formation rate and increased the total number of cells in porcine embryos. Further, DHM supplementation also improved glutathione levels and mitochondrial membrane potential; reduced natural reactive oxygen species levels in blastomeres and apoptosis rate; upregulated Nanog, Oct4, SOD1, SOD2, Sirt1, and Bcl2 expression; and downregulated Beclin1, ATG12, and Bax expression. Collectively, DHM supplementation regulated oxidative stress during IVC and could act as a potential antioxidant during in vitro porcine oocytes maturation.

Citric acid-based deep eutectic solvent (CA-DES) as a new soil detergent for the removal of cadmium from coking sites.

In order to solve the problem of soil pollution caused by excess heavy metals, cadmium (Cd), a novel soil-washing agent organic chelating acid-based deep eutectic solvent (OCA-DES), was investigated for the removal of Cd from the contaminated soil of coking plant. Four kinds of OCA-DES were prepared by mixing choline chloride (Ch-Cl) with four organic chelating acids (citric acid, oxalic acid, tartaric acid, and malic acid), respectively, to compare their washing efficiency of Cd from soil. The effects of washing operation conditions on the Cd removal efficiency were investigated. Side effects of citric acid-based deep eutectic solvent (CA-DES) on soil were analyzed using scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared (FTIR). The results showed that CA-DES had the best Cd removal efficiency and could reach as high as 93.75%, under ideal conditions. CA-DES mainly washed extractable and reducible Cd. The CA-DES washing process has less side effects on soil and hardly eroded the soil or changed the mineral structure of the soil. The main roles of CA-DES washing Cd include (1) hydrogen bonds capturing Cd; (2) the carboxyl group(-COOH) forming soluble chelate with Cd; and (3) releasing H+ ions in exchange for Cd. This study demonstrates that CA-DES, a novel soil-washing agent, has excellent removal of cadmium from soil and is environment-friendly.

Wedelolactone facilitates the early development of parthenogenetically activated porcine embryos by reducing oxidative stress and inhibiting autophagy.

Wedelolactone (WDL) is a coumaryl ether compound extracted from the traditional Chinese medicinal plant, Eclipta prostrata L. It is a natural polyphenol that exhibits a variety of pharmacological activities, such as anti-inflammatory, anti-free radical, and antioxidant activities in the bone, brain, and ovary. However, its effect on embryonic development remains unknown. The present study explored the influence of WDL supplementation of porcine oocytes culture in vitro on embryonic development and the underlying mechanisms and its effect on the levels of Kelch-like ECH-associated protein 1/nuclear factor-erythroid 2-related factor 2/antioxidant response element (Keap1/Nrf2/ARE). The results showed that WDL (2.5 nM) significantly increased the blastocyst formation rate, mitochondrial activity, and proliferation ability while reducing the reactive oxygen species accumulation, apoptosis, and autophagy. These findings suggested that WDL can enhance the growth and development of early porcine embryos to alleviate oxidative stress and autophagy through regulating NRF2 and microtubule-associated protein 1 light chain 3 (MAP1LC3) gene expression levels.

Oroxin A reduces oxidative stress, apoptosis, and autophagy and improves the developmental competence of porcine embryos in vitro.

Oroxin A (OA) is a flavonoid isolated from Oroxylum indicum (L.) Kurz that has various biological activities, including antioxidant activities. This study aimed to examine the viability of using OA in an in vitro culture (IVC) medium for its antioxidant effects and related molecular mechanisms on porcine blastocyst development. In this study, we investigated the effects of OA on early porcine embryo development via terminal deoxynucleotidyl transferase dUTP nick-end labeling, 5-ethynyl-2'-deoxyuridine labeling, quantitative reverse transcription PCR, and immunocytochemistry. Embryos cultured in the IVC medium supplemented with 2.5 µM of OA had an increased blastocyst formation rate, total cell number, and proliferation capacity, along with a low apoptosis rate. OA supplementation decreased reactive oxygen species levels while increasing glutathione levels. OA-treated embryos exhibited an improved intracellular mitochondrial membrane potential and reduced autophagy. Moreover, levels of pluripotency- and antioxidant-related genes were upregulated, whereas those of apoptosis- and autophagy-related genes were downregulated by OA addition. In conclusion, OA improves preimplantation embryonic development by reducing oxidative stress and enhancing mitochondrial function.

Prevalence of tobacco dependence and associated factors in China: Findings from nationwide China Health Literacy Survey during 2018-19.

Background: Tobacco dependence is the key barrier to successful smoking cessation. However, little is known about its prevalence, sociodemographic characteristics and determinants. We aimed to estimate the prevalence, associated factors and burden of tobacco dependence in China. Methods: During 2018-2019, the nationally representative 2018 China Health Literacy Survey (2018 CHLS) invited 87,708 participants to participate using a multistage stratified sampling method from 31 provinces (or equivalent) in mainland China, and 84,839 participants aged 20-69 with valid data were included in the analysis. We diagnosed tobacco dependence based on international criteria (ICD-10, DSM-4) and tailored to Chinese population according to China Clinical Guideline for Tobacco Cessation (2015 version). The prevalence of tobacco dependence was estimated overall and by sociodemographic factors. The Logistic regression was conducted to estimate odds ratios (OR) and 95% confidence intervals (CIs) for tobacco dependence and success of smoking cessation (being ex-smokers), with different levels of adjustment. These were used to estimate the total number of adults who were tobacco dependent in China. Findings: In China, the estimated prevalence of current smoking was 25.1%, significantly higher in men than in women (47.6% vs 1.9%). The prevalence of current smoking varied approximately 3-fold (12.9% to 37.9%) across 31 provinces of China. Among general population aged 20-69 years, the prevalence of tobacco dependence was 13.1% (95% CI:12.2-14.1). Among current smokers, the prevalence of tobacco dependence was 49.7% (46.5-52.9%), with no difference between men and women (49.7% vs 50.8%). The prevalence of tobacco dependence was associated significantly with smoking intensity, defined by pack-years (1.62 [1.54-1.70] per 10 pack-years), cigarettes smoked per day (2.01 [1.78, 2.27] per 10 cigarettes), and smoking starting age (0.93 [0.90, 0.97] per 5 years). Given smoking intensity, the prevalence of tobacco dependence also varied by age, gender, certain socioeconomic status and regions. Compared with those without tobacco dependence, ever smokers with tobacco dependence were less likely to be ex-smokers (2.88, 2.59-3.21). In China, 183.5 (170.4-197.4) million adults (177.5 million were men) were tobacco dependent in 2018. Interpretation: In China, tobacco dependence is highly prevalent, with approximately half of current smokers being addictive, highlighting the need for coordinated effort to improve awareness, diagnosis and treatment of tobacco dependence. Funding: Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS 2021-I2M-1-010), National Key R&D Program of China (grant no 2017YFC1309400), and National Natural Science Foundation of China (grant no 81720108001). Note: Chinese translation of abstract is available in appendix section.

Memantine Promotes Bactericidal Effect of Neutrophils Against Infection with Pseudomonas aeruginosa and Its Drug-Resistant Strain, by Improving Reactive Oxygen Species Generation.

Pseudomonas aeruginosa is an opportunistic pathogen, which usually presents multiple antibiotic resistance. Host-directed therapy involves modulating the host defense system and the interplay between innate and adaptive immunity is a new strategy for designing anti-infection drugs. Memantine (MEM), a drug used to treat Alzheimer's disease, has a good inhibitory effect on neonatal mice with Escherichia coli-associated bacteremia and meningitis; however, the inhibitory effect and mechanisms of MEM against P. aeruginosa infection remain unclear. Here, we investigated whether MEM could inhibit P. aeruginosa infection and explored the potential mechanisms. MEM significantly promoted the bactericidal effect of neutrophils against P. aeruginosa and its drug-resistant strain. The combination index of MEM and amikacin (AMK) was <1. In vivo experiments showed that the bacteremia and inflammation severities in the MEM-treated group were less than those in the untreated group, and the bacterial load in the organs was significantly less than that in the control group. Combining MEM with the reactive oxygen species (ROS) inhibitor, N-acetyl-l-cysteine, weakened the anti-infective effect of MEM. MEM increased the expression of NADPH p67phox and promoted neutrophilic ROS production. Deleting the p67phox gene significantly weakened the effects of MEM on ROS generation and improving bactericidal effect of neutrophils. In conclusion, MEM promoted the bactericidal effect of neutrophils against P. aeruginosa and its drug-resistant strain, and had a synergistic antibacterial effect when combined with AMK. MEM may exert its anti-infective effects by promoting neutrophilic bactericidal activity via increasing the expression level of p67phox and further stimulating ROS generation.

The experience of tobacco withdrawal symptoms among current smokers and ex-smokers in the general population: Findings from nationwide China Health Literacy Survey during 2018-19.

Objective: To clarify the extent to which smokers in the general population experience tobacco withdrawal symptoms and whether such experience differs in those who continue to smoke and those who stopped smoking. Methods: We included relevant questions in the nationally-representative China Health Literacy Survey (CHLS) conducted in 2018-2019. Among 87,028 participants, there were 22,115 ever-smokers aged 20-69 years who provided information on their smoking history and their experience of tobacco withdrawal symptoms. Multivariate logistic regressions were conducted to explore the association between withdrawal symptoms and other variables. Results: Among ever-smokers, there were 19,643 (88.8%) current smokers and 2,472 (11.2%) ex-smokers. Among current smokers, 61.3% reported having tried to quit smoking in the past. Overall, 61.1% of current smokers reported experiencing withdrawal symptoms: 69.9% of those who tried to quit smoking in the past and 47.5% of those who did not. A lower proportion of ex-smokers experienced withdrawal symptoms (46.3%) and the difference remained significant after controlling for demographic characteristics (OR = 1.76, 95% CI 1.62-1.93, P < 0.001). The most commonly reported withdrawal symptoms in both current smokers and ex-smokers were craving, restlessness and anxiety. In the multivariable-adjusted analyses, those who experienced withdrawal symptoms when they tried to quit smoking (OR: 2.05, 95% CI: 1.86-2.27) were less likely to successfully quit. Conclusions: The clinical picture of the tobacco withdrawal syndrome is the same in current smokers and in ex-smokers, but ex-smokers are less likely to have experienced it. The experience of discomfort when unable to smoke is common and seems likely to be a major factor contributing to maintaining smoking behavior not just among individuals seeking help with quitting smoking, but among smokers generally.

[Clinical Efficacy and Prognosis of Double-Hit Multiple Myeloma Patients with Deletion P53 Treated with Regimen Based on Bortezomib].

OBJECTIVE: To investigate the clinical efficacy and prognosis of double-hit multiple myeloma patients with deletion P53 treated with regimen based on bortezomib. METHODS: The ethnical data from 186 newly diagnosed MM patients hospitalized in the Department of Hematology of Harrison International Peace hospital from January 2012 to January 2019 were analyzed retrospectively. The fluorescent in situ hybridization (FISH) and G-binding staining were used to detect cytogenetic abnormalities (P53 deletion, lq21 amplification and IgH rearranagement) for analyses of complete remission (CR), overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) of patients treated with bortezomib for 4 circles. RESULTS: In 186 patients, simple P53 deletion was 14 cases, 1q21 amplification and P53 deletion were found in 11 cases (A group), t (14;16) and P53 deletion in 7 cases (B group), t (4;14) and P53 deletion in 9 cases (C group). The complete remission rate (CR%) of above-mentioned three groups was 27.27%, 28.57% and 33.33% respectively, and the ORR of the three groups was 54.54%, 57.14% and 55.56%, respectively, there was no statistically significant difference between the three groups (P＞0.05). The patients with 1q21 amplification and P53 deletion had shorter OS and PFS time (P=0.041, P=0.046). The double-hit patients with 1q21 amplification showed shorter OS time, compared with the patients with P53 deletion (P=0.027). The double-hit patients with t(14;16) and t(4;14) showed shorter OS time (P=0.871, P=0.276) and PFS time (P=0.955, P=0.379) than those of the patients with P53 deletion. CONCLUSION: P53 deletion and 1q21 amplification are an adverse prognostic factor of early recurrence and short lifetime in patients with newly diagnosed double-hit MM.

[Outcomes of DNMT3A+ Myelodysplastic Syndrome Patients Treated with Decitabine].

OBJECTIVE: To study therapeutic efficacy and side effects of single decitabine for DNMT3A+ myelodysplastic syndrome (MDS) patients. METHODS: The clinical characteristics, efficacy and side effects of 59 myelodysplastic syndrome patients received the decitabine therapy in our center from January 2015 to December 2018 were retrospectively analyzed. Based on gene mutations, these patients were divided into 2 groups: DNMT3A+ MDS patients (n=27) and DNMT3A- MDS patients (n=32). All patients in two groups were treated with decitabine for 4 circles. The efficacy and side effects in the two groups were compared. RESULTS: The median age of patients in DNMT3A+ MDS group was 56.2 (37-81) which was no statistic difference from DNMT3A- MDS group. And there was no statistical difference including age, white blood cells, hemoglobin and platelet count between the two groups (P＞0.05). The ORR and complete response (CR) rate of DNMT3A+ group were 70.37% and 40.74%, the ORR and CR rate of DNMT3A- group were 40.63% and 21.88% respectively. Significant differences were observed in ORR rate (P=0.035) between two groups. However, significant differences did not found in CR rate (P=0.159) between two groups, The similar adverse reaction was observed in DNMT3A+ and DNMT3A- MDS patients. Among the 59 patients, 21 patients showed TP53+ mutation. DNMT3A+/TP53+ MDS patients (n=13) had similar ORR and CR compared with the DNMT3A-/TP53+ MDS patients (n=8) (P＞0.05). The overall survival (OS) in DNMT3A+ MDS group and DNMT3A- MDS group were 29.1±13.4 months and 27.8±14.4 months, respectively, no significant differences between two groups were observed (P=0.475). CONCLUSION: Decitabine treatment is an effective and safe for DNMT3A+ MDS patients, but not shows better survival advantage.

[Survival and Prognosis of Patients with Nasal NK/T-Cell Lymphoma].

OBJECTIVE: To analyze the survival and prognosis of patients with nasal extranodal natural killer/T-cell lymphoma （ENKL）. METHODS: The clinical data of newly diagnosed 52 patients with nasal NK/T-cell lymphoma from June 2012 to June 2018 were selected. Univariate and multivariate analysis was performed on the relationship between different clinical factors and prognosis by Kaplan-Meier method and COX proportional hazard model. RESULTS: The median overall survival (OS) time of patients was 72 months. Univariate analysis showed that age, sex, IPI score, ECOG score, hemoglobin(Hb) level, clinical stage, and treatment pattern all associated with OS of nasal NK/T-cell lymphoma patients. Multivariate analysis showed that hemoglobin level, age and clinical stage were independent factors affecting OS of nasal NK/T lymphoma patients. CONCLUSION: Hemoglobin level, age and clinical stage can be used as indicators to evaluate the prognosis of nasal NK/T-cell lymphoma.

[Clinical Efficacy of Low-Dose Bortezomib-Based Triple Combination Therapy in the Treatment of Elderly Multiple Myeloma].

OBJECTIVE: To investigate the clinical efficacy and safety of low-dose bortezomib-based triple combination therapy in the treatment of elderly multiple myeloma(MM). METHODS: Fifty-eight patients with elderly multiple myeloma were selected. And according to the drug rigimen the patients were randomly divided into three groups. Group A: patients received low-dose bortezomib(0.7mg/m2) on day 1, 4, 8 and 11; cyclophosphamide (0.5 g/m2) d 1, d 8; dexamethasone d 1-2,d 4-5, d 8-11, d 11-12. Group B: patients received bortezomib (1.3 mg/m2) on day 1, 4, 8 and 11; cyclophosphamide (0.5 g/m2) d 1, d 8; dexamethasone d 1-2, d 4-5, d 8-11, d 11-12. Group C: patients received bortezomib(0.7 mg/m2) on day 1, 4, 8 and 11; dexamethasone d 1-2, d 4-5, d 8-11, d 11-12. All patients in three groups were treated for 4 circles. The efficacy and response of the three groups were compared. RESULTS: The complete remission (CR) rate in the three groups was 31.58%, 38.09% and 27.78%. And the overall response (ORR) rate of the three groups was 68.42%, 66.67% and 55.56%, there was no statistical difference among the three groups (P＞0.05). The Hb level in MM patients with anemia after treatment was higher than the basic value. There were no statistical differences in percapita red blood cell transfusion, the incidence of bone marrow suppression and infection during 4 courses treatment among 3 groups, but the incidence of peripheral neuropathy, gastrointestinal reaction and herper zoster in group A was significantly lower than that in group B and C, moreover there was statistical difference. After the follow-up for 1 year, there was no significant difference in the survival rate among 3 groups. CONCLUSION: The efficacy of low dose bortezomib-based triple combination therapy for the patients with elderly multiple mycloma is same efficacy as of standard dose bortezomib-based triple combination therapy, but the incidence of perpheral neuropathy, gastrointestinal reaction and herper zoster is lower, the patients have better torelonce to low dose bortezomib-based triple combination therapy regimen, suggesting that this therapy possesses the efficacy of less adverse reactions and more high safety in treatment of patients with elderly muitipe myelome.

[Expression Level and Clinical Significance of OTC4 Gene in Patients with Myelodysplastic Syndromes].

OBJECTIVE: To investigate the expression characteristics and clinical value of OTC4 gene in patients with myelodysplastic syndrome (MDS). METHODS: Sixty-five patients with MDS were selected from June 2017 to April 2018, and 39 healthy subjects were selected as control group. Mononuclear cells were isolated from bone marrow collected by aseptic puncture. The OTC4 gene level of MDS patients was detected by RT-PCR, and the OTC4 protein of MDS patients was detected by Western blot. The survival curve of MDS patients was drawn by Kaplan-Meier. Cox multivariate analysis was used to analyze the independent prognostic factors. RESULTS: The relative expression level of OTC4 gene in MDS patients was significantly higher than that in the control group (P＜0.05). Western blot showed that the expression level of OTC4 protein in MDS patients was higher than that in the control group (P＜0.05). OTC4 gene expression level closely related with the leukocyte count, and the level of hemoglobin, and lactate dehydrogenase and platelet count in MDS patients (P＜0.05). CR rate of MDS patients with low OTC4 gene expression was 54.8%, which was higher than that of high OTC4 gene expression group (P＜0.05), while HI, SD and PD rates of MDS patients with low OTC4 gene expression were 9.7%, 12.9% and 6.5% respectively, which were lower than those of high OTC4 gene expression group (P＜0.05). Kaplan-Meier survival analysis showed that OS and DFS in patients with low OTC4 gene expression were superior to those with high OTC4 gene expression (P＜0.05). Multivariate Cox regression analysis showed that leukocyte count and OTC4 gene were independent influencing factors for OS (P＜0.05), platelet level and OTC4 gene expression were independent influencing factors for DFS (P＜0.05). CONCLUSION: OTC4 gene closely relates with the severity of MDS. The patients with lower expression of OTC4 gene have better prognosis, the detection of OTC4 gene has higher clinical value for evaluating the prognosis of MDS patients.