Dissecting Causal Relationships Between Gut Microbiota, Blood Metabolites, and Stroke: A Mendelian Randomization Study / 대한뇌졸중학회지

Background@#and Purpose We investigated the causal relationships between the gut microbiota (GM), stroke, and potential metabolite mediators using Mendelian randomization (MR). @*Methods@#We leveraged the summary statistics of GM (n=18,340 in the MiBioGen consortium), blood metabolites (n=115,078 in the UK Biobank), and stroke (cases n=60,176 and controls n=1,310,725 in the Global Biobank Meta-Analysis Initiative) from the largest genome-wide association studies to date. We performed bidirectional MR analyses to explore the causal relationships between the GM and stroke, and two mediation analyses, two-step MR and multivariable MR, to discover potential mediating metabolites. @*Results@#Ten taxa were causally associated with stroke, and stroke led to changes in 27 taxa. In the two-step MR, Bifidobacteriales order, Bifidobacteriaceae family, Desulfovibrio genus, apolipoprotein A1 (ApoA1), phospholipids in high-density lipoprotein (HDL_PL), and the ratio of apolipoprotein B to ApoA1 (ApoB/ApoA1) were causally associated with stroke (all P<0.044). The causal associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were validated using the weighted median method in an independent cohort. The three GM taxa were all positively associated with ApoA1 and HDL_PL, whereas Desulfovibrio genus was negatively associated with ApoB/ApoA1 (all P<0.010). Additionally, the causal associations between the three GM taxa and ApoA1 remained significant after correcting for the false discovery rate (all q-values <0.027). Multivariable MR showed that the associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were mediated by ApoA1 and HDL_PL, each accounting for 6.5% (P=0.028) and 4.6% (P=0.033); the association between Desulfovibrio genus and stroke was mediated by ApoA1, HDL_PL, and ApoB/ApoA1, with mediated proportions of 7.6% (P=0.019), 4.2% (P=0.035), and 9.1% (P=0.013), respectively. @*Conclusion@#The current MR study provides evidence supporting the causal relationships between several specific GM taxa and stroke and potential mediating metabolites.

Association between the Neutrophil-to-lymphocyte Ratio and New-onset Subclinical Macrovascular and Microvascular Diseases in the Chinese Population / 生物医学与环境科学（英文）

OBJECTIVE@#The association between neutrophil-to-lymphocyte ratio (NLR) with subclinical macrovascular and microvascular diseases has been less investigated. We sought to examine the association between NLR and new-onset subclinical macrovascular and microvascular abnormalities in the Chinese population.@*METHODS@#From a community cohort, we included 6,430 adults aged ≥ 40 years without subclinical macrovascular and microvascular diseases at baseline. We measured subclinical macrovascular and microvascular abnormalities separately using the ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), and albuminuria.@*RESULTS@#During a mean follow-up of 4.3 years, 110 participants developed incident abnormal ABI, 746 participants developed incident elevated baPWV, and 503 participants developed incident albuminuria. Poisson regression analysis indicated that NLR was significantly associated with an increased risk of new-onset abnormal ABI, elevated baPWV, and albuminuria. Compared to overweight/obese participants, we found a much stronger association between NLR and subclinical vascular abnormalities in participants with normal weight. Furthermore, we found an interaction between the NLR and body mass index (BMI) on the risk of new-onset abnormal ABI ( P for interaction: 0.01).@*CONCLUSION@#NLR was associated with subclinical macrovascular and microvascular diseases in the Chinese population. Furthermore, in participants with normal weight, the association between NLR and subclinical vascular abnormalities was much stronger.

Association of Visit-to-Visit Variabilities in Metabolic Factors with Chronic Kidney Disease in Chinese Adults Living in Shanghai / 生物医学与环境科学（英文）

Objective@#This study aimed to examine the association of visit-to-visit variabilities in metabolic factors with chronic kidney disease (CKD) in Shanghai community residents.@*Methods@#We used data from a cohort study of community residents who participated in three examinations in 2008, 2009, and 2013, respectively. Fasting plasma glucose (FPG) level, blood pressure (BP), and lipid levels were determined in 2,109 participants at all three visits, and CKD was evaluated between the second and the third visits. Visit-to-visit variabilities in metabolic factors were described by coefficients of variation (CV) at three visits. A variability score was calculated by adding the numbers of metabolic factors with a high variability defined as the highest quartile of CV. CKD was defined as the estimated glomerular filtration rate < 60 mL/min per 1.73 m @*Results@#A total of 200 (9.5%) participants had CKD at the third visit. Compared with the lowest quartile of CV, the highest quartile was associated with a 70% increased risk of CKD for FPG [odds ratio, @*Conclusion@#The visit-to-visit variabilities in metabolic factors were significantly associated with the risks of CKD in Shanghai community residents.

Inverted U-Shaped Associations between Glycemic Indices and Serum Uric Acid Levels in the General Chinese Population: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study / 生物医学与环境科学（英文）

Objective@#The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population.@*Methods@#The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models.@*Results@#A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices).@*Conclusion@#An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.

Relationship between famine exposure in early life and type 2 diabetes mellitus in adulthood / 中华内分泌代谢杂志

Objective:To investigate the correlation between exposure to famine in early life and later risk of type 2 diabetes in adulthood.Methods:A cluster sampling method was used to include 8 868 residents who were lived in the Jiading community of Shanghai during the Great Famine from 1959 to 1962 in China. Subjects were divided into non-exposed group, fetal exposure group, childhood exposure group, and adolescent exposure group. Logistic regression model was used to analyze the relationship between famine exposure in early life and the risk of type 2 diabetes in adulthood. Results:Famine exposure during childhood and adolescent both increased the risk of developing type 2 diabetes in adulthood in women. No significant correlation was observed in men. In subjects with less physical activity and lower education level, the risk of developing type 2 diabetes mellitus in adulthood was significantly higher in the famine-exposed group than that of non-exposed groupand the interactions were statistically significant.Conclusion:Early life famine exposure increases the risk of developing type 2 diabetes in adults, especially in women.

Serum uric acid and risk of incident diabetes in middle-aged and elderly Chinese adults: prospective cohort study / 医学前沿

The association between serum uric acid and the risk of incident diabetes in Chinese adults remains unknown. This study aimed to investigate this association in a community-dwelling population aged ≥ 40 years in Shanghai, China. Oral glucose tole3rance test was conducted during baseline and follow-up visits. Relative risk regression was utilized to examine the associations between baseline gender-specific serum uric acid levels and incident diabetes risk. A total of 613 (10.3%) incident diabetes cases were identified during the follow-up visit after 4.5 years. Fasting plasma glucose, postload glucose, and glycated hemoglobin A1c during the follow-up visit progressively increased across the sex-specific quartiles of serum uric acid (all Ps < 0.05). The incidence rate of diabetes increased across the quartiles of serum uric acid (7.43%, 8.77%, 11.47%, and 13.43%). Multivariate adjusted regression analysis revealed that individuals in the highest quartile had 1.36-fold increased risk of diabetes compared with those in the lowest quartile of serum uric acid (odds ratio (95% confidence interval) = 1.36 (1.06-1.73)). Stratified analysis indicated that the association was only observed in women. Accordingly, serum uric acid was associated with the increased risk of incident diabetes among middle-aged and elderly Chinese women.

Peripheral Artery Disease and Risk of Fibrosis Deterioration in Nonalcoholic Fatty Liver Disease: A Prospective Investigation / 生物医学与环境科学（英文）

Objective@#Liver fibrosis is an important predictor of mortality in nonalcoholic fatty liver disease (NAFLD). Peripheral artery disease (PAD) and liver fibrosis share many common metabolic dysfunctions. We aimed to explore the association between PAD and risk of fibrosis deterioration in NAFLD patients.@*Methods@#The study recruited 1,610 NAFLD patients aged ≥ 40 years from a well-defined community at baseline in 2010 and followed up between August 2014 and May 2015. Fibrosis deterioration was defined as the NAFLD fibrosis score (NFS) status increased to a higher category at the follow-up visit. PAD was defined as an ankle-brachial index of 1.40.@*Results@#During an average of 4.3 years' follow-up, 618 patients progressed to a higher NFS category. PAD was associated with 92% increased risk of fibrosis deterioration [multivariable-adjusted odds ratio ( ): 1.92, 95% confidence interval ( ): 1.24, 2.98]. When stratified by baseline NFS status, the for progression from low to intermediate or high NFS was 1.74 (95% : 1.02, 3.00), and progression from intermediate to high NFS was 2.24 (95% : 1.05, 4.80). There was a significant interaction between PAD and insulin resistance (IR) on fibrosis deterioration ( for interaction = 0.03). As compared with non-PAD and non-IR, the coexistence of PAD and IR was associated with a 3.85-fold (95% : 2.06, 7.18) increased risk of fibrosis deterioration.@*Conclusion@#PAD is associated with an increased risk of fibrosis deterioration in NAFLD patients, especially in those with IR. The coexistence of PAD and IR may impose an interactive effect on the risk of fibrosis deterioration.

Chinese Herbal Medicine for Osteosarcoma in the Mouse: A Systematic Review and Meta-Analysis / 中国结合医学杂志

OBJECTIVE@#To summarize and critically assess the inhibitory effects of Chinese herbal medicine (CHM) on tumor volume and tumor weight for the treatment of osteosarcoma (OS) in mouse models.@*METHODS@#PubMed, Embase, Web of Science, China Knowledge Resource Integrated Database (CNKI), Wanfang Database, VIP Database, and Chinese BioMedical (CBM) were searched since their inception dates to March 10, 2016. Two reviewers independently selected the controlled studies estimating effects of CHM on mouse OS by administration in vivo. A pair-wise meta-analysis was performed. Twenty-five studies with adequate randomization were included in the systematic review.@*RESULTS@#CHM may significantly inhibit OS growth in mice, as assessed using the tumor weight [20 studies, n=443; 290 for CHM and 153 for the control: pooled mean difference (MD)=-2.90; 95% confidence interval (Cl): -3.50 to -2.31: P<0.01], tumor volume (16 studies, n=382; 257 for CHM and 125 for the control; pooled MD =-2.57; 95% Cl: -3.33 to -1.80; P<0.01) and tumor growth inhibition rate.@*CONCLUSION@#CHM could significantly inhibit the growth of OS in mouse models, which might be supportive for the design of preclinical and clinical trials in future.

Research status on calorie restriction on glucose metabolism in patients with type 2 diabetes / 中华内分泌代谢杂志

Calorie restriction is one of the diet therapies for people with diabetes.Calorie restriction can reduce weight and improve glycemic control,but the long-term effects are controversial.The effects can be influenced by the degree of calorie restriction,the study duration,and the types of food used for intervention.The mechanism includes the improvement of β cell function and insulin sensitivity.The existing problems are compliance of patients,long-term effects,possible adverse effects,and the lack of high-quality studies.In this review,we introduced the current research progress of calorie restriction on glucose metabolism in patients with type 2 diabetes.

Association between Coronary Atherosclerotic Plaque Composition and Cardiovascular Disease Risk / 生物医学与环境科学（英文）

OBJECTIVE@#The objective of this study is to determine whether coronary atherosclerotic plaque composition is associated with cardiovascular disease (CVD) risk in Chinese adults.@*METHODS@#We performed a cross-sectional analysis in 549 subjects without previous diagnosis or clinical symptoms of CVD in a community cohort of middle-aged Chinese adults. The participants underwent coronary computed tomography (CT) angiography for the evaluation of the presence and composition of coronary plaques. CVD risk was evaluated by the Framingham risk score (FRS) and the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score.@*RESULTS@#Among the 549 participants, 267 (48.6%) had no coronary plaques, 201 (36.6%) had noncalcified coronary plaques, and 81 (14.8%) had calcified or mixed coronary plaques. The measures of CVD risk including FRS and ASCVD risk score and the likelihood of having elevated FRS significantly increased across the groups of participants without coronary plaques, with noncalcified coronary plaques, and with calcified or mixed coronary plaques. However, only calcified or mixed coronary plaques were significantly associated with an elevated ASCVD risk score [odds ratio (OR) 2.41; 95% confidence interval (CI) 1.09-5.32] compared with no coronary plaques, whereas no significant association was found for noncalcified coronary plaques and elevated ASCVD risk score (OR 1.25; 95% CI 0.71-2.21) after multivariable adjustment.@*CONCLUSION@#Calcified or mixed coronary plaques might be more associated with an elevated likelihood of having CVD than noncalcified coronary plaques.

Ideal Cardiovascular Health is Inversely Associated with Subclinical Atherosclerosis: A Prospective Analysis / 生物医学与环境科学（英文）

OBJECTIVE@#Ideal cardiovascular health (CVH) could predict a lower risk of developing cardiovascular diseases. This study was conducted to investigate the association between ideal CVH and subclinical atherosclerosis in a population cohort of Chinese adults aged ⪖ 40 years.@*METHODS@#This study was designed as a cross-sectional analysis of 8,395 participants who had complete data at baseline and a prospective analysis of 4,879 participants who had complete data at 4.3 years of follow-up. Ideal CVH metrics were defined according to the American Heart Association. Subclinical atherosclerosis was evaluated by plaques in carotid arteries, carotid intima-media thickness (CIMT), brachial-ankle pulse wave velocity (baPWV), and urinary albumin-to-creatinine ratio (UACR).@*RESULTS@#Both the prevalence and incidence of atherosclerosis measures were found to be decreased with increasing numbers of ideal CVH metrics at baseline (all P values for trend < 0.01). The levels of CIMT and UACR at follow-up showed an inverse and significant association with the numbers of ideal CVH metrics at baseline (both P values for trend < 0.05) but a borderline significant association with baPWV (P for trend = 0.0505). Taking participants with 0-1 ideal metric as reference, we found that participants with 5-6 ideal metrics had significantly lower risks of developing carotid plaques (odds ratio, OR = 0.46; 95% confidence interval, CI 0.27-0.79), increased CIMT (OR = 0.60; 95% CI 0.42-0.84), and increased baPWV (OR = 0.57; 95% CI 0.34-0.97) after full adjustments. A significant interactive effect of age and CVH was detected on CIMT and baPWV progression (both P values for interaction < 0.05).@*CONCLUSION@#The numbers of ideal CVH metrics showed a significant and inverse association with the risk of developing subclinical atherosclerosis in middle-aged and elderly Chinese adults, whereas its dose-response effect was attenuated in individuals aged ≥ 60 years and partially weakened in male participants.

Association between Lipoprotein (a) Levels and Metabolic Syndrome in a Middle-aged and Elderly Chinese Cohort / 生物医学与环境科学（英文）

OBJECTIVE@#The association between lipoprotein (a) [Lp(a)] levels and metabolic syndrome (MetS) remains uncertain, especially in the Asian population. The purpose of this study was to demonstrate the association between Lp(a) levels and MetS in a middle-aged and elderly Chinese cohort.@*METHODS@#A cross-sectional study of 10,336 Chinese adults aged 40 years or older was conducted in Jiading District, Shanghai, China. Logistic regression analysis was used to evaluate the association between serum Lp(a) levels and MetS.@*RESULTS@#In the overall population, 37.5% of participants had MetS. Compared with individuals in the lowest quartile of serum Lp(a) levels, those in the highest quartile had a lower prevalence of MetS (30.9% vs. 46.9%, P for trend < 0.0001). Multivariate logistic regression analyses showed that compared with participants in the bottom quartile of serum Lp(a) levels, those in the top quartile had decreased odds ratio (OR) for prevalent MetS [multivariate-adjusted OR 0.45 (95% confidence interval 0.39-0.51); P < 0.0001]. Additionally, Lp(a) level was conversely associated with the risk of central obesity, high fasting glucose, high triglycerides, and low HDL cholesterol, but not with hypertension. Stratified analyses suggested that increasing levels of Lp(a) was associated with decreased risk of MetS in all the subgroups.@*CONCLUSION@#Serum Lp(a) level was inversely associated with the risk of prevalent MetS in a middle-aged and elderly Chinese cohort.

Type 2 diabetes is causally associated with depression: a Mendelian randomization analysis / 医学前沿

Type 2 diabetes (T2D) has been associated with a high prevalence of depression.We aimed to determine the causal relation by performing a Mendelian randomization (MR) study using 34 T2D risk genetic variants validated in East Asians as the instrumental variable (IV). An MR analysis was performed involving 11 506 participants from a large longitudinal study. The T2D genetic risk score (GRS) was built using the 34 typical T2D common variants. We used T2D_GRS as the IV estimator and performed inverse-variance weighted (IVW) and Egger MR analysis. The T2D_GRS was found to be associated with depression with an OR of 1.21 (95% CI: 1.07-1.37) after adjustments for age, sex, body mass index, current smoking and drinking, physical activity, education, and marital status. Using T2D_GRS as the IV, we similarly found a causal relationship between genetically determined T2D and depression (OR: 1.84, 95% CI: 1.25-2.70). Though we found no association between the combined effect of the genetic IVs for T2D and depression with EggerMR(OR: 0.95, 95%CI: 0.42-2.14), we found an association for T2D and depression with IVW (OR: 1.75, 95% CI: 1.31-2.46) after excluding pleiotropic SNPs. Overall, the MR analyses provide evidence inferring a potential causal relationship between T2D and depression.

Traditional Chinese medicine combined with radiotherapy for treatment of middle and advanced esophageal neoplasms: an analysis of prognostic factors / 肿瘤研究与临床

Objective To explore the prognostic factors of middle and advanced esophageal neoplasms treated by traditional Chinese medicine combined with radiotherapy.Methods A total of 462 esophageal neoplasms patients treated by traditional Chinese medicine combined with radiotherapy from March 2009 to March 2012 in Civil Administration Hospital of Hebei Province were retrospectively analyzed.The overall median survival time and the survival rate of 1,3 and 5 years were calculated by using life table.Log-rank test was used for single-factor analysis and Cox model was used for multiple-factor analysis.Results The median survival time of 462 esophageal neoplasm patients was 24.2 months (12.9-36.6 months).The survival rate of 1,3 and 5 years was 80.3 ％,30.6 ％ and 10.5 ％ respectively.Single-factor analysis showed that the age (x2 =89.773,P =0.000),tumor diameter (x2 =102.373,P =0.000),clinical staging (x2 =128.903,P =0.000),concomitant with other diseases (x2 =65.366,P =0.000) and the short term effect (x2 =64.948,P =0.000) were associated with prognosis of middle and advanced esophageal neoplasms treated by traditional Chinese medicine combined with radiotherapy.Multiple-factor analysis showed that the age (RR =1.625,95 ％ CI 1.251-2.111,P=0.000),clinical staging (RR =2.437,95 ％ CI 1.874-3.168,P=0.000),concomitant with other diseases (RR =1.1.628,95 ％ CI 1.278-2.076,P =0.000) and the short term effect(RR =1.865,95 ％ CI 1.594-2.182,P =0.000) were the independent prognosis factors for middle and advanced esophageal neoplasms treated by traditional Chinese medicine combined with radiotherapy.Conclusion Elderly patients,esophageal neoplasms in stage Ⅲ,concomitant with other diseases and poor short-term effect could influence the prognosis of the patients with middle and advanced esophageal neoplasms treated by traditional Chinese medicine combined with radiotherapy.

Association between gallstone and non-alcoholic fatty liver disease in middle-aged and elderly Chinese in Shanghai local communities / 中华内分泌代谢杂志

Objective To investigate the association between gallstone and non-alcoholic fatty liver disease (NAFLD)in middle-aged and elderly Chinese. Methods A cross-sectional study was conducted in 8934 Chinese adults from Jiading District, Shanghai. Questionnaire interview, anthropometric measurements, biochemical evaluation, and abdominal ultrasonography were performed in all the participants. Results Compared with participants without gallstone,individuals with gallstone had significantly higher prevalence of NAFLD(28.8% and 42.9%,respectively;P<0.01). Using participants without gallstone as the reference,participants with gallstone were associated with an increased risk of NAFLD after adjustment for multiple covariatesodds ratios(OR)and 95% confidence interval(CI)was 1.39(1.45-1.69). In addition,compared with participants without cholecystectomy, participants with cholecystectomy were associated with an increased risk of NAFLD(OR=1. 44, 95% CI 1. 04-1.99). Conclusion The presence of gallstone and cholecystectomy were positively associated with NAFLD in middle-aged and elderly Chinese.

Association of low-grade albuminuria with carotid intima-media thickness / 中华内分泌代谢杂志

Objective To analyze the association of elevated carotid intima-media thickness(CIMT)with low-grade albuminuria in a community-based population. Methods A total of 10 375 participants aged 40 years or older were recruited using cluster sampling from Jiading district, Shanghai. Standardized questionnaires were adopted to collect information on health status and lifestyles. Anthropometric measurements including weight, height, and blood pressure, and biochemical tests for blood and urine were performed. CIMT was detected by B-mode ultrasound examinations. 9 523 subjects were included for final analysis. All these subjects were divided into 4 groups according to sex-specific urinary albumin to creatinine ratio ( UACR ) quartiles. CIMT≥upper decile of the population was defined as elevated CIMT and low-grade albuminuria was defined as UACR≥sex-specific upper quartile. The relationship between UACR and CIMT was investigated by multiple logistic regression analysis. Results The prevalence of elevated CIMT in this population aged 40 years or older with albuminuria in normal range was 21. 44%. Comparing to participants without elevated CIMT, those with elevated CIMT showed higher level of UACR (4. 79 vs 4. 51 mg/g, P<0. 01). The metabolic status was deteriorated with the increment of UACR level. The prevalences of elevated CIMT were 18. 99%, 19. 24%, 20. 20%, and 27. 33% from the lowest to highest UACR quartile, respectively(Ptrend<0. 01). After adjusting for some conventional cardiovascular risk factors, multiple logistic regression revealed that compared with the participants in the lowest quartile of UACR, those in the highest quartile had a 1. 25-fold risk of elevated CIMT. Conclusions This study shows that low-grade albuminuria is positively associated with elevated CIMT, independent of conventional cardiovascular risk factors in middle-aged and elderly adults.

Effects of Aptamer-siRNA Nucleic Acid Compound on Growth and Apoptosis in Myeloid Leukemia Cell Line K562 / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the effects of aptamer-siRNA nucleic acid compound on growth and apoptosis in myeloid leukemia cell line K562.</p><p><b>METHODS</b>the changes of cellular morphology and structure were observed by using fluorescence microscope, laser confocal microscope, JEM-4000EX transmission electron microscopy; MTT assay were performed to evaluate the sensibility of K562 cells to aptamer-siRNA compound, the apoptosis was detected by DNA gel electro-phoresis.</p><p><b>RESULTS</b>The remarkably changes of morphology and structure of K562 cells treated with 200 µmol/L aptamer-siRNA were observed under fluorescence microscopy and electromicroscopy. As compared with control, the aptamer-siRNA compound showed more inhibitory effect on K562 cells and there was significant difference (P<0.05). The MTT assay showed that the IC50 value of aptamer-siRNA compound for K562 cells was 150 µmol/L. According to agarose gel electrophoresis observation, when the aptamer-siRNA compound showed effect on K562 cells, the typical DNA lader could be observed.</p><p><b>CONCLUSION</b>The aptamer-siRNA compound can significantly induce K562 cell apoptosis, and provide reference for gene therapy of patients with chronic myelocytic lenkemia.</p>

Once- versus twice-weekly Bortezomib induction therapy with dexamethasone in newly diagnosed multiple myeloma / 华中科技大学学报（医学）（英德文版）

In this study, we administered a modified schedule of weekly intravenous Bortezomib at 1.6 mg/m(2) with dexamethasone (BD) and compared it to the standard 1.3 mg/m(2) twice-weekly BD regimen in Chinese patients with newly diagnosed multiple myeloma (MM). We assessed the difference in efficacy, safety profile and survival between the once-weekly and twice-weekly cohorts (13 vs. 24 patients). The over response rate was similar with both arms of the study, being 77% in the once-weekly schedule and 74.9% in the twice-weekly schedule (P=0.690). The median overall survival was not reached in either schedule. Also, the median progression-free survival and duration of response of the once-weekly schedule did not significantly differ from those of the twice-weekly schedule (8 months vs.10 months, P=0.545 and 6 months vs.7 months, P=0.467 respectively). Peripheral sensory neuropathy and grade 3/4 hematologic toxic effects were more frequently reported in the twice-weekly schedule than the once-weekly schedule, but there was no statistically significant difference. This preliminary experience in Chinese patients with newly diagnosed MM indicated that once-weekly infusion of Bortezomib plus dexamethasone may improve safety without affecting outcome.

Hepatitis B virus reactivation in a chronic myeloid leukemia patient treated with imatinib mesylate / 中华医学杂志(英文版)

Imatinib mesylate is a molecular targeted agent for treating chronic myeloid leukemia (CML) and gastrointestinal stromal tumor. Although imatinib mesylate is not regarded as an immunosuppressive agent, few studies have also shown that it may impair immune response. In this report, we present a case of transient hepatitis B virus (HBV) reactivation during imatinib mesylate treatment for CML.

Reactivation of chronic hepatitis B infection related to imatinib mesylate therapy in patients with chronic myeloid leukemia: two cases report and literatures review / 中华血液学杂志

<p><b>OBJECTIVE</b>To probe the cause for triggering HBV reactivation and possible management of the chronic hepatitis B individuals received imatinib.</p><p><b>METHODS</b>This study presented two cases of transient hepatitis B virus (HBV) reactivation and hepatic dysfunction during oral imatinib for chronic myeloid leukemia (CML) and made a literatures review about the pathogenesis, possible prophylactic and therapeutic management of such chronic hepatitis B individuals receiving imatinib.</p><p><b>RESULTS</b>Two CML patients, without prior liver dysfunction but with chronic HBV infection, suffered from transient HBV reactivation occurred during oral imatinib. Both of them finally obtained good outcome following the additional oral nucleotide antiviral therapy.</p><p><b>CONCLUSION</b>It remained unclear whether imatinib induced the reactivation of HBV in patients with a latent HBV infection. From our study, all candidates receiving oral imatinib should be screened for HBsAg and anti-HBc antibodies prior to initiation of imatinib. Prophylactic antiviral therapy should be offered to HBV-infected individuals along with a close monitoring for signs of reactivation.</p>