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Osteoarthritis (OA) causes joint pain and disability due to the abnormal production of inflammatory cytokines and reactive oxygen species (ROS) in chondrocytes, leading to cell death and cartilage matrix destruction. Selenium (Se) intake can protect cells against oxidative damage. It is still unknown whether Se supplementation is beneficial for OA. This study investigated the effects of Se on sodium iodoacetate (MIA)-imitated OA progress in human chondrocyte cell line (SW1353 cells) and rats. The results showed that 0.3 μM of Se treatment could protect SW1353 cells from MIA-induced damage by the Nrf2 pathway by promoting the gene expression of glutathione-synthesis-related enzymes such as the glutamate-cysteine ligase catalytic subunit, the glutamate-cysteine ligase modifier subunit, and glutathione synthetase. In addition, glutathione, superoxide dismutase, glutathione peroxidase, and glutathione reductase expressions are also elevated to eliminate excessive ROS production. Moreover, Se could downregulate NF-κB, leading to a decrease in cytokines, matrix proteases, and glycosaminoglycans. In the rats, MIA-induced cartilage loss was lessened after 2 weeks of Se supplementation by oral gavage; meanwhile, glutathione synthesis was increased, and the expressions of pro-inflammatory cytokines were decreased. These results suggest that Se intake is beneficial for OA due to its effects of decreasing cartilage loss by enhancing antioxidant capacity and reducing inflammation.

Objective: To investigate the effect of metformin and arsenic trioxide on KG1a cells proliferation of acute myeloid leukemia and its possible mechanism., Methods: CCK-8 method was used to detect the killing effect of metformin, arsenic trioxide and combined application on KG1a cells. Annexin V-FITC/PI Dual Stain Flow Cytometry was used to detect the effect of combined application on apoptosis of KG1a cells. Western blot was used to detect the expression of intracellular apoptosis-,autophagy-related protein., Results: Metformin and arsenic trioxide alone or in combination could inhibit the proliferation of KG1a cells and induce apoptosis of KG1a cells, and the proliferation inhibition rate and apoptosis rate in the combined drug group were higher than those in the drug group alone( P <0.05). The combination of drugs induced upregulation of Caspase 8 protein and P62 protein expression and was higher than that in the drug group alone( P <0.05)., Conclusion: Metformin can synergize with arsenic trioxide to kill KG1a cells, and its mechanism of action may be related to inducing apoptosis and enhancing autophagy.

The hippocampus is the brain's center for episodic memories. Its subregions, the dentate gyrus and CA1-3, are differentially involved in memory encoding and recall. Hippocampal principal cells represent episodic features like movement, space, and context, but less is known about GABAergic interneurons. Here, we performed two-photon calcium imaging of parvalbumin- and somatostatin-expressing interneurons in the dentate gyrus and CA1-3 of male mice exploring virtual environments. Parvalbumin-interneurons increased activity with running-speed and reduced it in novel environments. Somatostatin-interneurons in CA1-3 behaved similar to parvalbumin-expressing cells, but their dentate gyrus counterparts increased activity during rest and in novel environments. Congruently, chemogenetic silencing of dentate parvalbumin-interneurons had prominent effects in familiar contexts, while silencing somatostatin-expressing cells increased similarity of granule cell representations between novel and familiar environments. Our data indicate unique roles for parvalbumin- and somatostatin-positive interneurons in the dentate gyrus that are distinct from those in CA1-3 and may support routing of novel information., (© 2024. The Author(s).)

Introduction: Allogeneic hematopoietic cell transplantation (alloHCT) is increasingly offered to older adults, and its potential impact on cognition in this population is understudied. This work aims to evaluate the ability of cancer-specific geriatric assessments (cGA) and a global frailty index based on accumulation of deficits identified in the cGA to predict the risk of cognitive decline after alloHCT in older adults., Materials and Methods: AlloHCT recipients aged 50 years or older completed a cGA, including a cognitive evaluation by the Blessed Orientation Memory Concentration (BOMC) test, at baseline prior to alloHCT and then at 3, 6, and 12 months after transplant. Baseline frailty was assessed using a deficit accumulation frailty index (DAFI) calculated from the cGA. A multinomial logit model was used to examine the association between predictors (individual cGA measures, DAFI) and the following three outcomes: alive with stable or improved cognition, alive with cognitive decline, and deceased. In post-hoc analyses, analysis of variance was used to compare BOMC scores at baseline, 3, 6, and 12 months across frailty categories., Results: In total, 148 participants were included, with a median age of 62 (range 50-76). At baseline, 12% had cognitive impairment; at one year, 29% of survivors had improved BOMC scores, 33% had stable BOMC, and 37% had worse BOMC. Prior to transplant, 25% were pre-frail and 11% were frail. Individual baseline cGA measures were not associated with cognitive change at one year as assessed by BOMC. Adjusting for age, sex, and education, those who were frail at baseline were 7.4 times as likely to develop cognitive decline at one year than those who were non-frail, although this finding did not reach statistical significance (95% confidence interval [CI] 0.74-73.8, p = 0.09). The probability of being alive with stable/improved cognition at 12 months for the non-frail, pre-frail, and frail groups was 43%, 34%, and 8%, respectively., Discussion: Baseline geriatric measures and frailty were not significantly associated with cognitive change as assessed by BOMC in adults aged 50 or older after alloHCT. However, the study was underpowered to detect clinically meaningful differences, and future work to elucidate potential associations between frailty and cognitive outcomes is warranted., Competing Interests: Declaration of Competing Interest Dr. Olin reports other from Cellectis, personal fees from Actinium, personal fees from Astellas, personal fees from Abbvie, outside the submitted work., (Published by Elsevier Ltd.)

As allogeneic hematopoietic cell transplantation (alloHCT) is increasingly offered to older adults, geriatric assessment (GA) has been identified as a useful tool for predicting outcomes, particularly functional status. However, very few studies have examined the longitudinal change in GA measures in the post-alloHCT period. The objectives of this study were to describe the longitudinal change in GA and quality of life (QoL) measures after alloHCT and to identify predictors of greater functional decline post-transplantation. In this single-center prospective cohort study, patients age ≥50 years scheduled for alloHCT completed a cancer-specific GA and the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) survey at baseline prior to alloHCT and then at 3, 6, and 12 months post-transplantation. Changes in GA and QoL measures at each post-transplantation time point (3, 6, and 12 months) compared to baseline were analyzed using paired t-tests. Exploration of potential predictors of greater post-transplantation functional decline, as measured by instrumental activities of daily living (IADL) and the Medical Outcomes Study Physical Health scale (MOS-PH), were examined using linear regression and the chi-square 2-sample test of proportions. Mean functional status generally exhibited a pattern of decline at 3 to 6 months post-alloHCT, with recovery to near baseline by 12 months. Mean mental health and emotional QoL were lowest at baseline and improved at all post-transplantation time points. Differences in baseline clinical characteristics were not associated with any differences in functional trajectories. Differences in baseline GA measures-patient-rated Karnofsky Performance Status, IADL, MOS-PH, Timed-Up-and-Go, Blessed Orientation-Memory-Concentration test, and Mental Health Inventory 5-also did not predict greater functional decline at 3 months. Patients whose IADL was improved or maintained at 3 months generally maintained their functional status at 6 and 12 months. Similarly, most patients who had an IADL decline at 3 months still had a functional decline at 6 months, although a proportion did have functional recovery by 12 months. Compared with patients who had improved/maintained IADL at 3 months, those with a decline in IADL at 3 months were significantly more likely to have persistent functional decline at 6 months (P < .0001) and 12 months (P = .02). In older alloHCT recipients, mean functional status declines short term after alloHCT with the possibility of recovery by 6 to 12 months, whereas mean mental and emotional health improve post-alloHCT. Functional decline at 3 months post-alloHCT is associated with persistent functional decline at 12 months., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Non-Hodgkin lymphoma (NHL) is a disease of older adults, with a median age at diagnosis of 67 years. Treatment in older adults with NHL is challenging. The aging process is associated with a decline in functional reserve that varies among individuals, and results in an increasing risk of treatment-related toxicity and mortality. Chronological age and performance status fail to capture the multidimensional and heterogeneous nature of the aging process. A geriatric assessment (GA) screens multiple geriatric domains and provides a more accurate assessment of functional reserve. Several abbreviated GA tools have been developed for use in oncology clinics and help identify patients at high risk for chemotherapy-related toxicity and mortality. In this review, we explore GA tools validated for use in patients with NHL. We discuss the evidence behind GA-guided treatment in NHL and present a suggested approach to assessing frailty in this patient population., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: Patients with non-Hodgkin lymphoma (NHL) have a median age of 67, with 70% surviving over 5 years. Chemotherapy for aggressive NHL includes cyclophosphamide, anthracycline, and high doses of corticosteroids, which can impair bone health. By reviewing clinical characteristics and standard-of-care CT scans, we evaluate the prevalence and incidence of fractures and the clinical correlates of fractures in patients treated for aggressive B-cell NHL., Methods: We retrospectively reviewed patients seen at the University of California San Francisco lymphoma clinic from January 1, 2016, to March 31, 2017 who had (1) aggressive B-cell NHL, (2) received first-line therapy with R-CHOP-like regimens, and had (3) CT scans pre- and post-treatment available for review. Associations between clinical variables and vertebral, rib, and pelvic fracture outcomes were assessed, and multivariate logistic regression models were used to identify predictors of prevalent and incident fractures., Results: We identified 162 patients who met the inclusion criteria. Median age at diagnosis was 60 years. Of the 162 patients, 38 patients (28%) had prevalent fractures prior to receiving chemotherapy. Within 1 year after treatment, 16 patients (10%) developed new fractures. Having a prevalent fracture strongly predicted developing a new fracture after treatment, with incident fractures occurring in 12 of 38 patients with prevalent fractures versus 4 of 124 without prevalent fractures (odds ratio 10.45, p<0.0005)., Conclusion: Our results suggest that patients with aggressive B-cell NHL who receive R-CHOP-like therapy should be screened for fractures prior to treatment and those with existing fractures should be considered for therapy to decrease risk of new fractures., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Polypharmacy is common in older adults with cancer, but there is little evidence evaluating the impact of polypharmacy and other medication hazards on allogeneic hematopoietic cell transplantation (alloHCT) outcomes. A small number of prior studies have evaluated the impact of potentially inappropriate medication (PIM) use in the setting of alloHCT, with mixed results. We evaluated the effects of pre-alloHCT polypharmacy, PIM use, and drug-drug interactions (DDIs) on post-alloHCT outcomes, including overall survival (OS), progression-free survival (PFS), non-relapse mortality (NRM), hospital length of stay (LOS), number of non-hematologic grade ≥3 adverse events (AEs) within 100 days after alloHCT, and number of readmissions within the first 100 days after alloHCT. The study population was a single-center prospective cohort of 148 patients ≥ 50 years of age. Pre-alloHCT medication lists were retrospectively collected from the electronic medical record, including both scheduled and as-needed medications. PIMs were defined by a modified 2019 American Geriatrics Society Beers Criteria. DDIs were analyzed using Lexi-Interact. Polypharmacy was common in this population; the median number of medications was seven (range, 0 to 23). Fifty-two patients (35%) were prescribed nine or more medications, and 73 patients (49%) had at least one PIM prescribed. The median number of DDIs was three (range, 0 to 31), and the most common severity was major (48%). After adjusting for age and Hematopoietic Cell Transplant Comorbidity Index (HCTCI), both the number of all medications and number of scheduled medications were associated with inferior OS, with hazard ratios (HRs) of 1.07 (95% confidence interval [CI], 1.01 to 1.12; P = .02) and 1.08 (95% CI, 1.00 to 1.15; P = .04), respectively. Receipt of nine or more scheduled medications was associated with inferior OS (HR, 1.92; 95% CI, 1.11 to 3.32; P = .02). The number of PIMs was also significantly associated with OS (HR, 1.24; 95% CI, 1.00 to 1.54, P = .05). After adjusting for age, HCTCI, and total number of medications, a greater number of DDIs were significantly associated with longer hospital length of stay (difference, 0.74 days; 95% CI, 0.09 to 1.40, P = .03). In adjusted analyses, there were no significant polypharmacy-related predictors of NRM, LOS, or non-hematologic grade ≥3 AEs. These data demonstrate the utility of pre-alloHCT polypharmacy, PIM use, and DDIs as important prognostic factors and support routine pre-alloHCT medication review by physicians and pharmacists with a goal of appropriate de-prescribing where possible., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Sudden cardiac death (SCD) is an uncommon but significant cause of death in the young. Citywide cardiac screening of school-aged children has been performed in Taipei since 1989. In this study, we investigate the efficacy of this screening method for identifying those at high risk of SCD., Methods: This study analyzed the data from the results of cardiac screening for school-aged children in Taipei from 2003 to 2014. The cardiac screening included: Stage I, questionnaire surveys, simplified phonocardiography test and simplified electrocardiography (ECG) test; Stage II, physical examination and auscultation by a pediatric cardiologist for all children who had abnormal findings in stage I screening; Stage III, referral to a pediatric cardiologist for further examinations. Logistic regression and decision tree analyses were performed., Results: A total of 566,447 students were screened, of whom 685 were identified as being at high risk of SCD. The most common causes of being at high risk of SCD included Wolff-Parkinson-White syndrome, long QT syndrome, cardiomyopathy and Marfan's syndrome. Using logistic regression analysis, the simplified ECG test was identified as being the most effective tool (odds ratio = 16.4, p < 0.001) and past history as the second most crucial factor (odds ratio = 3.95, p < 0.001) for detecting a high risk of SCD. Decision tree analysis showed that serial studies with a past history and the simplified ECG test could accurately identify those at high risk of SCD., Conclusions: Questionnaire survey and simplified electrocardiography test-based cardiovascular screening in school-aged children can identify those at high risk of SCD.

Objective: To explore an effective method for inducing a rat model with hyperuricemia in a short period and assess the effects of the model. Methods: Sprague-Dawley rats were adopted as donors and randomly divided into control group (CT group, n=6) and 5 model groups (M1-M5 groups, n=8 in each group). M1 group (gavage with 10 g/kg yeast extracts and 100 mg/kg adenine, twice per day, 300 mg/kg oxonic acid potassium by intraperitoneal injection, in the 7 th day of model inducing), M2 group (gavage with 10 g/kg yeast extracts and 100 mg/kg adenine, twice per day, 300 mg/kg oxonic acid potassium by intraperitoneal injection, in the 1 st , 3 rd and 7 th day of model inducing),M3 group (gavage with 10 g/kg yeast extracts and 100 mg/kg adenine, twice per day, 300 mg/kg oxonic acid potassium by intraperitoneal injection, once per day during the model inducing), M4 group (gavage with 20 g/kg yeast extracts and 100 mg/kg adenine, twice per day, 300 mg/kg oxonic acid potassium by intraperitoneal injection, once per day during the model inducing), M5 group (gavage with 30 g/kg yeast extracts and 100 mg/kg adenine, twice per day, 300 mg/kg oxonic acid potassium by intraperitoneal injection, once per day during the model inducing), and group CT (gavaged with equal volume sterilized water and intraperitoneal injected with normal saline according to the weight and at the same frequency as the model groups). The model inducing lasted for 7 days. After the inducing was finished, blood and 24-hour urine were sampled for uric acid and creatinine determination. Then rats were maintained for 2 weeks and blood and 24-hour urine samples were collected, the concentration of uric acid and creatinine were detected. The kidney and stomach were weighed,morphological changes in kidney were observed. Results: After model inducing, the body weight of rats in all model groups was lower than that of the control group (P＜0.01). Deaths occurred in all the rats with model treatments except M2. M4 and M5 groups were failed to be analyzed because of the high mortality, model 1 and 3 groups had 4 and 2 deaths, respectively. The uric acid levels in blood and urine of the model groups were significantly elevated (P＜ 0.01) at the end of model inducing. The model 2 group's blood uric acid was highest among the model groups (P＜0.05). It sustained a higher concentration than CT group in the three model groups after 2 weeks feeding (P＜0.05). The kidneys in model groups obviously swelling and were heavier than CT group (P＜0.01). The inflammation and structural damages were observed in kidneys of all model groups. Conclusion: The yeast extract (10 g/kg), adenine (100 mg/kg) gavage combined with intraperitoneal injections(the 1 st , 3 rd , 7 th day during inducing) of potassium oxonate can be an rapid and effective method for inducing the rat model with hyperuricemia, which can be suggested to the related research.

Allogeneic hematopoietic cell transplantation (alloHCT) has been increasingly offered to older adults with hematologic malignancies. However, optimal methods to determine fitness for alloHCT have yet to be defined. We evaluated the ability of a comprehensive geriatric assessment (CGA) to predict post-alloHCT outcomes in a single-center prospective cohort study of patients age 50 years and older. Outcomes included overall survival (OS), progression-free survival (PFS), and nonrelapse mortality (NRM). A total of 148 patients were included, with a median age of 62 years (range, 50 to 76 years). In multivariate regression analysis, several CGA measures of functional status were predictive of post-alloHCT outcomes, after adjusting for traditional prognostic factors. Any deficit in instrumental activities of daily living (IADL) was associated with inferior OS (hazard ratio [HR], 1.81, 95% confidence interval [CI], 1.07 to 3.08; P = .03) and PFS (HR, 1.85; 95% CI, 1.15 to 2.99; P = .01). A Medical Outcomes Study Physical Health scale (MOS-PH) score <85 was associated with inferior OS (HR, 1.96; 95% CI, 1.13 to 3.40; P = .02), PFS (HR, 1.75; 95% CI, 1.07 to 2.88; P = .03), and increased NRM (subdistribution HR, 2.57; 95% CI, 1.12 to 5.92; P = .03). MOS-PH score was also associated with the number of non-hematologic grade ≥3 adverse events within the first 100 days after alloHCT (rate ratio, 1.61; 95% CI, 1.04 to 2.49; P = .03). These findings support previous work suggesting that IADL is an important prognostic tool prior to alloHCT. MOS-PH is newly identified as an additional metric to identify older patients at higher risk of poor post-alloHCT outcomes, including toxicity and NRM., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Hematologic malignancies are common and difficult to treat in older adults. In this review, we focus on recent updates in diseases with several novel agents relevant to older adults-acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and multiple myeloma (MM)., Recent Findings: In AML, CPX-351 offers a new induction chemotherapy for secondary AML that prolongs survival, and venetoclax and IDH inhibitors are efficacious and well tolerated. In CLL, chemoimmunotherapy is being replaced by monoclonal antibodies and small molecule inhibitors that are more effective and better tolerated. In MM, new immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies have expanded treatment options for older patients. The introduction of novel agents has dramatically shifted the landscape of therapeutic options for older adults with hematologic malignancies. Clinical trials in older adults are needed to expand treatment options for these patients.

Background and Aim: Fibrosis index based on the four factors (FIB-4) and aspartate aminotransferase to platelet ratio index (APRI) were not well validated in patients with chronic hepatitis B (CHB). The aim of this study was to validate the performances of these indexes and construct novel indexes for liver fibrosis assessment., Methods: A total of 1438 consecutive antivirus treatment-naïve patients with CHB were analysed, and two novel indexes (named HeBCI and HeBFI) were derived for cirrhosis and significant fibrosis detection., Results: For cirrhosis, the area under receiver operating characteristic curves (AUROCs) were 0.841 for HeBCI, 0.708 for FIB-4 and 0.623 for APRI in the model set, and 0.779, 0.690, 0.595 in the validation set. For significant fibrosis, the AUROCs were 0.781 for HeBFI, 0.693 for APRI and 0.641 for FIB-4 in the model set, and 0.776, 0.729, 0.641 in the validation set. HeBCI determined 750 (52.2%) patients as having cirrhosis or non-cirrhosis with an accuracy of 86%. HeBFI detected 673 (46.8%) patients with or without significant fibrosis with an accuracy of 76.6%., Conclusions: As economical and convenient indexes, HeBCI and HeBFI are suitable to serve as outpatient tools for detecting significant fibrosis and cirrhosis to reduce the need of liver biopsy significantly in resource-limited settings., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

High performance microprobes for combined sensing of glucose and choline were fabricated using microcontact printing (μCP) to transfer choline oxidase (ChOx) and glucose oxidase (GOx) onto targeted sites on microelectrode arrays (MEAs). Most electroenzymatic sensing sites on MEAs for neuroscience applications are created by manual enzyme deposition, which becomes problematic when the array feature size is less than or equal to ∼100 μm. The μCP process used here relies on use of soft lithography to create features on a polydimethylsiloxane (PDMS) microstamp that correspond to the dimensions and array locations of targeted, microscale sites on a MEA. Precise alignment of the stamp with the MEA is also required to transfer enzyme only onto the specified microelectrode(s). The dual sensor fabrication process began with polyphenylenediamine (PPD) electrodeposition on all Pt microelectrodes to block common interferents (e.g., ascorbic acid and dopamine) found in brain extracellular fluid. Next, a chitosan film was electrodeposited to serve as an adhesive layer. The two enzymes, ChOx and GOx, were transferred onto different microelectrodes of 2 × 2 arrays using two different PDMS stamps and a microscope for stamp alignment. Using constant potential amperometry, the combined sensing microprobe was confirmed to have high sensitivity for choline and glucose (286 and 117 μA mM cm-2, respectively) accompanied by low detection limits (1 and 3 μM, respectively) and rapid response times (≤2 s). This work demonstrates the use of μCP for facile creation of multianalyte sensing microprobes by targeted deposition of enzymes onto preselected sites of a microelectrode array.

Epirubicin is an anthracycline and is widely used in tumor treatment, but has toxic and undesirable side effects on wide range of cells and hematopoietic stem cells (HSC). Osteoblasts play important roles in bone development and in supporting HSC differentiation and maturation. It remains unknown whether epirubicin-induced bone loss and hematological toxicity are associated with its effect on osteoblasts. In primary osteoblast cell cultures, epirubicin inhibited cell growth and decreased mineralization. Moreover, epirubicin arrested osteoblasts in the G2/M phase, and this arrest was followed by apoptosis in which both the extrinsic (death receptor-mediated) and intrinsic (mitochondrial-mediated) apoptotic pathways were evoked. The factors involved in the extrinsic apoptotic pathway were increased FasL and FADD as well as activated caspase-8. Those involved in the intrinsic apoptotic pathway were decreased Bcl-2; increased reactive oxygen species, Bax, cytochrome c; and activated caspase-9 and caspase-3. These results demonstrate that epirubicin induced osteoblast apoptosis through the extrinsic and intrinsic apoptotic pathways, leading to the destruction of osteoblasts and consequent lessening of their functions in maintaining bone density and supporting hematopoietic stem cell differentiation and maturation.

Obesity is a public health problem in both developed and developing countries, and the negative effects of obesity on reproductive physiology have been highlighted recently. We evaluated the effects of porcine obesity index, sex hormones, and peptide hormones on litter size in various breeds of minipigs. Blood samples were collected from sedated 8-,10-, and 12-mo-old minipigs to measure preovulatory levels of sex hormones (follicle-stimulating hormone, luteinizing hormone, estradiol, progesterone, testosterone, and prolactin) and peptide hormones (insulin-like growth factor, glucagon, cortisol, growth hormone, free thyroxine, free triiodothyronine, insulin, and leptin). We also measured weight, abdominal circumference, neck circumference, and body length and then calculated the porcine obesity index. Data were analyzed by one-way ANOVA, and means were compared by least significance difference testing. Pearson correlation between parameters and litter size was analyzed. Prepregnancy porcine obesity index and litter size were negatively correlated in primiparous minipigs. Litter size was influenced by luteinizing hormone, estradiol, progesterone, testosterone, prolactin, follicle-stimulating hormone, cortisol, insulin-like growth factor 1, growth hormone, free thyroxine, insulin, and leptin. In conclusion, prepregnancy obesity reduces litter size in primiparous minipigs.

Treatment for the older adult with acute myeloid leukemia (AML) is challenging, due to both more aggressive disease biology as well as patient-related risk factors that limit tolerance of intensive chemotherapy. The use of prognostic models and comprehensive geriatric assessments can help hematologists evaluate the suitability of intensive chemotherapy for individual patients. For older patients considered fit for intensive chemotherapy, standard induction therapy should be given, followed by consideration of reduced intensity allogeneic stem cell transplantation. Patients considered unfit for intensive therapy are standardly treated with hypomethylating agents. Several new therapeutic agents have shown promising results either by improving intensive chemotherapy (CPX-351), by improving upon lower intensity therapy (venetoclax, antibody drug conjugates), or by targeting somatic mutations (FLT3 inhibitors and others)., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Cancer cells proliferate rapidly and are resistant to cell death, relying on aggravated glycolysis to satisfy their increased demand for energy and biosynthetic precursors. However, this process may create unfavorable microenvironments, such as increased acidity, leading to cytotoxicity. Our previous study demonstrated that arecoline induces anoikis of HA22T/VGH hepatoma cells. The present study aimed to examine if arecoline induced anoikis is related to the glycolytic pathway and explore the underlying mechanisms. Methods: HA22T/VGH cells were treated with arecoline and changes in the glycolytic end products lactate and ATP, glycolytic-related gene expression, intracellular and extracellular pH, pH-regulating gene expression, reactive oxygen species (ROS) levels, intracellular Ca 2+ concentration ([Ca 2+ ]i) and mitochondrial membrane potential were examined, relative to untreated cells. Cell viability and morphology were also assessed. Results: Arecoline increased lactate and ATP production through induction of glycolytic genes, including glucose transporter 3 (Glut3), hexokinase 1 (HK1), hexokinase 2 (HK2), and pyruvate kinase (PK). The intracellular pH was not changed, despite increased lactate levels, implying that intracellular H + was exported out of the cells. mRNA expression of pH regulators including monocarboxylate transporter 1 and 4 (MCT 1 and 4), sodium bicarbonate cotransporter 1 (NBC1), carbonic anhydrases (CA) IX and XII and vacuolar ATPase (V-ATPase) were down-regulated. Na + /H + exchanger 1 (NHE1) mRNA levels remained unchanged while Na + /Ca 2+ exchanger (NCX) was up-regulated and eventually [Ca 2+ ]i was increased. ROS generation was increased and mitochondrial membrane potential was decreased followed by cell detachment and death. Addition of 2-deoxy-d-glucose, a glucose competitor that interferes with glycolysis, attenuated arecoline induction of lactate [Ca 2+ ]i, ROS and cell detachment. Similarly, ROS scavengers could block the effects of arecoline. Conclusions: This study demonstrated that arecoline induced glycolysis and modulated the mRNA expression of pH-regulator genes in HA22T/VGH cells. This phenomenon led to the elevation of [Ca 2+ ]i, ROS generation, and subsequent cell detachment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Traditional Chinese medicine (TCM; zhōng yī) syndrome groups are based on the symptoms of human diseases and guide the use of Chinese herbs. The aim of this study was to examine the effects of TCM syndrome groups on biochemical characteristics and quality of life (QOL) in women with metabolic syndrome (MS). Among the 1080 registered female patients screened at our outpatient clinic, a total of 322 women aged between 18 and 65 years and meeting the requirements of MS were enrolled. All the patients were asked to fill out a questionnaire on metabolic TCM syndrome groups and a questionnaire on the QOL, the Medical Outcomes Study (MOS) Short Form-12 (SF-12). Data of biochemical characteristics were collected at the same time. The present study showed MS women in TCM syndrome groups had significantly lower physical and mental component scores in SF-12 compared with those not in TCM syndrome groups. We also found MS patients in TCM syndrome groups, except Kidney Deficiency syndrome, showed higher body mass indexes, waist circumference, and hip circumference. However, there was almost no difference in most biochemical characteristics between TCM syndrome groups. The MS patients diagnosed as belonging to TCM syndrome groups had poor QOL.

Objective: To investigate surgical approach for paralytic strabismus with lateral rectus muscles paralysis and evaluate its clinical effects., Methods: Design retrospective, observational case series. 28 patients (31 eyes) who underwent augmented partial rectus muscle transposition (APRMT) in the treatment of paralytic strabismus with lateral rectus muscles paralysis from May 2009 to May 2011 at Eye & ENT Hospital of Fudan University were included in this study. The following data were analyzed: (1) The procedure that was performed, (2) The angle of deviation of primary position, (3) The presence of compensatory head posture, (4) The presence of diploma in the primary position, (5) The binocular single visual fields, (6) The motility of the affected eye., Results: According to the results of rectus muscle forced traction test and examination before and after operation, among 31 eyes in 28 patients, 8 eyes were treated with APRMT, 10 eyes were treated with recession of antagonistic muscle of paralytic rectus muscle combined with APRMT, 7 eyes were treated with APRMT and recession of yoke muscle, 6 eyes were treated with APRMT and recession of yoke muscle combined with recession of antagonistic muscle. 17 among 28 patients were orthotopic in the primary position while others were in mild under correction with deviation no more than 10 prism degrees during 5 months (range: 3-8 months) follow-up in average. The diploma and abnormal head posture were eliminated in 26 patients except one patient who was appeared with 10 prism degrees under correction postoperatively and was resolved by wearing prisms thereafter. Binocular single visual fields were extended from 27.0° ± 6.4 ° preoperatively to 40.5° ± 4.8 ° postoperatively (t = -34.692, P < 0.001). Ocular movement was improved from -4.9 ± 0.4 to -2.9 ± 0.9 postoperatively (t = -13.418, P < 0.001)., Conclusions: APRMT can safely and effectively correct the primary position in paralytic strabismus with lateral rectus muscles paralysis, eliminate the presence of diploma in primary position and abnormal head posture, and improve the ability of the ocular movement, furthermore, significantly expand the scope of binocular single visual fields. The results also demonstrate that rectus muscle forced traction test is a key measurement to determine the surgical procedure.

Objective: Several studies have shown that soy isoflavones have estrogen-like activities and might constitute an alternative to hormone replacement treatment. The present study investigated the effects of soy isoflavones alone and combined with vitamin D3 on prevention of bone loss., Methods: Sprague-Dawley rats were sham-operated (n = 8) or ovariectomized (OVX; n = 40), and then the OVX rats were randomly assigned to five groups that were untreated or treated for 14 wk with vitamin D3, 17β-estradiol, soy isoflavone extract (SIE), or vitamin D3 plus SIE. The effects of the isoflavones and 1α,25(OH)(2)D(3) on cultured osteoblasts and osteoclasts also were investigated., Results: In OVX rats, the bone mineral density and trabecular bone volume loss were improved by 17β-estradiol, SIE, or SIE plus vitamin D3 treatment. SIE treatment was more effective than vitamin D3 or 17β-estradiol in inhibiting increases in serum tumor necrosis factor-α levels and osteoblast osteoprotegerin expression. SIE plus vitamin D3 was more effective in increasing osterix expression than each alone. Bone cell cultures showed that the isoflavones induced preosteoblasts to differentiate into osteoblasts and increased osteoblast mineralization. Isoflavones inhibited preosteoclasts and osteoclast proliferation and decreased osteoclast resorption. The combination of isoflavones plus 1α,25(OH)(2)D(3) showed additive effects on the increase in cell proliferation of cultured preosteoblasts., Conclusion: Treatment with soy isoflavones might be an alternative to hormone replacement therapy in decreasing bone loss from postmenopausal estrogen deficiency. In addition, there are further effects on increasing transcription factor osterix expression and preosteoblast proliferation when these were combined with vitamin D3., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To investigate the effect of Shenshuai Yangzhen Capsule (SYC) on hypothalamic leptin-neuropeptide Y (NPY) and proopiomelanocortin (POMC) axes in chronic renal failure (CRF) rats with malnutrition (MN)., Methods: Forty-two male SD rats of SPF grade were established into CRF-MN model by 5/6 nephrectomy and 4% casein diet, the happening time of MN in them was recorded. Rats successfully modeled were randomized into three groups, 11 rats in Group A treated with SYC, 11 in group B treated with composite alpha-keto acid and 12 in Group C was untreated. Besides, a normal control group was set up with 8 healthy rats. After being treated for 4 weeks, the renal function related indices, including serum creatinine (Scr), blood urea nitrogen (BUN), 24 hour urine protein (24 h Upro), albumin (ALB), haemoglobin (Hb) insulin like growth factor-1 (IGF-1), total cholesterol (TC) and triglyeride (TG) were measured, and body weight, food intake in rats were observed dynamically, blood leptin and NPY level in rats were determined by radioimmunoassay; mRNA expressions of OB-Rb, NPY and POMC in hypothalamus were detected with RT-PCR., Results: CRF rats revealed MN at the end of 10th week after modeling. Compared with Group C, the condition of MN in Group A was significantly improved, showing increase of food intake and body weight (P < 0.05), marked improvement of renal function (P < 0.05), decrease of LP and NPY levels in plasma (P < 0.05), as well as up-regulated NPY mRNA expression and down-regulated mRNA expressions of OB-Rb and POMC in hypothalamus (P < 0.01)., Conclusion: SYC can improve the malnutrition condition in rats with CRF, which is possibly by way of depressing OB-Rb and POMC mRNA expression and upgrading NPY mRNA expression in hypothalamus.

Objective: To investigate the effects of capsule of Shenshuai Yangzhen, a preparation of traditional Chinese medicine, on malnutrition rats with chronic renal failure (CRF)., Methods: SD rats received 5/6 nephrectomy for preparation of CRF models, and fed 4% casein at the same time. Observed when malnutrition began. Those consistents with malnutrition of CRF condition were randomized into model control group, Ketosteril group, Shenshuai Yangzhen group, and normal control group. After 4-weeks treatment as indicated, The blood parameters, like blood serum albumin (ALB), type-1 insulin like growth factor (IGF-1), total cholesterol (TC), triglyeride (TG), urea nitrogen (BUN), serum creatinine (Scr), haemoglobin (Hb), 24 hour urineprotein (24hUpr) and weight were determined. Nephrotic tissue was observed by microscope (included HE and PAS)., Results: Malnutrition situation in CRF rats began at the end of 10-weeks. After 4-weeks treatment, weight in Shenshuai Yangzhen group were higher significantly (P < 0.05). Compared with model control group, blood serum BUN (P < 0.05), SCr (P < 0. 05) and 24h Upr (P < 0.001) in Shenshuai Yangzhen group were significantly lower with substantially elevated blood serum ALB, Hb, IGF-1 (P < 0.01; P < 0.001; P < 0.001, respectively). Pathology of Shenshuai Yangzhen group was a meliorated significantly after treated., Conclusion: Capsule of Shenshuai Yangzhen has a possible therapic effect on improving malnutrition in rats with renal insufficiency.

Objectives: To identify the risk factors of postoperative pulmonary complications (PPC) after surgery for gallstone disease., Methods: A total of 544 patients undergoing open surgery for gallstone disease were retrospectively studied. Univariate and multivariate logistic regression were used to analyze each factor., Results: There were 24 factors relating to PPC in univariate logistic analysis. And multivariate logistic analysis identified 5 independent risk factors associated with PPC, including perioperative aerosol therapy (OR = 5.906), duration of postoperative antacids therapy (OR = 1.145), duration of operation (OR = 1.011), preoperative serum albumin (OR = 0.689), postoperative analgesia (OR = 0.059), Logistic regression equation for predicting the risk of PPC was P(1) = 1/[1 + e-(- 9.803 + 1.776 x A + 0.135 x B + 0.011 x C - 0.372 x D - 2.835 x E)]., Conclusion: Perioperative aerosol therapy, duration of postoperative antacids therapy, duration of operation, preoperative serum albumin and postoperative analgesia were independent risk factors associated with PPC in patients undergoing surgery for gallstone disease.

Objective: To investigate the risk factors for postoperative pulmonary complications (PPC) after gastroduodenal operation., Methods: From December 1999 to December 2003, clinical data of 508 patients undergoing gastroduodenal operation were analyzed retrospectively. Risk factors for PPC were screened., Results: The complication rate of PPC was 25.8% (131/508). Multivariate logistic regression analysis revealed that age (OR=1.052), history of respiratory diseases (OR=2.915), serum albumin level (OR=0.995), length of intratracheal intubation (OR=1.005), length of nasogastric intubation (OR=1.059) and length of postoperative mechanical ventilation (OR=1.367) were risk factors for PPC., Conclusion: Patients with old age, lower serum albumin level, intraoperative or postoperative nasogastric intubation, intratracheal intubation or long-term mechanical ventilation were more prone to develop PPC.

Aim: To identify the risk factors for postoperative pulmonary complications (PPC) after gastrointestinal surgery., Methods: A total of 1 002 patients undergoing gastrointestinal surgery in the Second Affiliated Hospital, Sun Yat-Sen University, during December 1999 and December 2003, were retrospectively studied., Results: The overall incidence of PPC was 22.8% (228/1,002). Multivariate logistic analysis identified nine risk factors associated with PPC, including age odds ratio (OR = 1.040) history of respiratory diseases (OR = 2.976), serum albumin (OR = 0.954), chemotherapy 2 wk before operation (OR = 3.214), volume of preoperative erythrocyte transfusion (OR = 1.002), length of preoperative antibiotic therapy (OR=1.072), intraoperative intratracheal intubation (OR = 1.002), nasogastric intubation (OR = 1.050) and postoperative mechanical ventilation (OR = 1.878). Logistic regression equation for predicting the risk of PPC was P(1) = 1/[1+e(-(-3.488+0.039 x Y+1.090 x Rd+0.001 x Rbc-0.047 x Alb+0.002 x Lii+0.049 x Lni+0.630 x Lmv+0.070 x Dat+1.168 x Ct))]., Conclusion: Old patients are easier to develop PPC.

Background: Primary liver cancer (PLC) is one of the most frequently seen tumors in China. Thirty years ago, patients with PLC were often detected at relatively late stage, with a palpable mass or marked clinical symptoms and poor prognosis. In the past 30 years, the diagnosis and treatment of PLC have been greatly improved with better prognosis., Methods: In order to study the changes of PLC during the 30 years, the clinical data of 3250 patients with PLC from 10 medical institutions of China were collected, analyzed, and compared with those of 3254 PLC patients before the 30 years., Results: In the 3250 patients aged 1-80 years, with an average age of 49.1 years, the male to female ratio (2.3:1) was lower than that before the 30 years. 73.5% of the 3250 patients sought medical advice within 3 months after the onset of the disease in contrast to 63.8% before the 30 years. Compared with those patients before the 30 years the symptoms and signs were alleviated generally. The HBsAg positive rate was 81.0%, but the HCV-Ab positive rate was 13.2%. The AFP level in 75% of patients was elevated, but in the remaining 25% was normal. 1912 patients (58.8%) were confirmed pathologically. Among them 1755 patients (91.8%) had hepatocellular carcinoma. The overall resection rate was 46.3%. Those who had early, middle, late stage carcinoma accounted for 29.9%, 51.5%, and 18.6% respectively in contrast to 0.4%, 47.0%, and 52.6% reported before the 30 years. The 1-, 3-, 5-year survival rates of the patients were 66.1%, 39.7%, and 32.5% respectively, whereas 93.5%, 70.1%, and 59.1% for the early stage patients, and 65.3%, 30.5%, and 23.5% for the middle stage patients. The half and 1-year survival rates of the late stage patients were 52.5%, and 14.7%, respectively., Conclusion: Comparison with the clinical data before and after the 30 years show that PLC can be diagnosed early. More PLC patients tend to undergo resection while receiving a better conservative treatment, which ensures a prognosis.

Objective: To clarify three-grade criteria of curative resection for primary liver cancer (PLC) and evaluate their clinical significance., Methods: Criteria of curative resection of PLC were summed up to three grades. Grade I: complete removal of all gross tumors with no residual tumor at the excision margin. Grade II: on the basis of Grade I, there was no extrahepatic metastasis, no hilar lymph node metastasis, no tumor thrombus in the main trunks and their primary tributaries of the portal vein, common hepatic duct, hepatic vein and vena cava inferior, and the tumor was not more than two in number. Grade III: in addition to the above criteria, AFP dropped to normal level (in patients with elevated AFP before surgery) within 2 months after operation, and no residual tumor upon diagnostic imaging. A total of 354 cases with PLC who had their liver resected was reviewed. Patients in each grade were divided into two portions depending on whether the treatment was curative or palliative., Results: The survival of patients receiving curative treatment was better than those receiving palliative treatment (P < 0.01). This was true for patients whose treatment belonged to anyone of the three-grade criteria. The survival was improved along with the promotion of curative criteria used. The 5-year survival rate of Grade I, II and III patients undergone curative resection was 43.2%, 51.2% and 64.4%, respectively (P < 0.01)., Conclusion: 1. The three-grade criteria may be used for judging the radicality of tumor resection for PLC. 2. The more stringent the criteria used, the better the survival would be. 3. Adopting high-grade criteria to select cases, to guide operation and postoperative follow-up would improve the results of liver resection for PLC.

Objective: To investigate measures to prevent the outbreak of severe acute respiratory syndrome (SARS) in healthcare workers in isolation units., Methods: The architectural factors and the infection of healthcare workers in different wards in our hospital between 30 January 2003 and 30 March 2003 were analyzed., Results: Four kinds of isolation wards were evaluated, including the ward where the thirty-first bed lied in on the twelfth floor, the laminar flow ward in the intensive care unit (ICU) where the tenth bed lied in on the fifteenth floor, the ward where the twenty-seventh bed lied in on the thirteenth floor of Building A, and thirty wards on the fourteenth to eighteenth floors of Building B. The ratios (m2/m3) of the area of the ventilation windows to the volume of the room were 0, 0, 1:95 and 1:40, respectively. Numbers of SARS cases in the wards mentioned above were 1, 1, 1 and 96, respectively. The total lengths (hour) of hospitalization were 43, 168, 110 and 1,272, respectively. The infection rates of the healthcare workers in the areas mentioned above were 73%, 32%, 28% and 2%, respectively. The difference of the infection rates was of statistical significance., Conclusion: In addition to strict personal protective measures, isolation of SARS cases in wards with high ratio of the area of ventilation windows to the volume of the room and good ventilation may be the key to preventing the outbreak of SARS in healthcare workers in isolation units.

Objective: To study the changes of the clinical aspects of primary liver cancer (PLC) during the past 30 years., Methods: The clinical data of 3,250 patients with PLC, from 10 regions of China were collected, analyzed, and compared with the clinical data of 3254 PLC cases 30 years before., Results: The 3,250 patients were aged 1- 80, with an average age of 49.1 years, younger than those 30 years before (43.7 years). The male to female ratio was 2.3:1, lower than that 30 years before (7.7:1). 73.5% of them sought medical advice within 3 months after the onset in comparison of 63.8% 30 years before. Compared with those 30 years before the symptoms and signs were alleviated in general. The HBsAg positive rate was 81.0%, the HCV-Ag positive rate was 13.2%, and the alpha-fetoprotein positive rate was 75%. 1912 cases underwent pathological examination of which 91.8% were diagnosed as with hepatocellular carcinoma. The overall resection rate was 46,3%. Those of early, median, and late stages accounted for 29.9%, 51.5%, and 18.6% respectively in comparison with the rates of 0.4%, 47.0%, and 52.6% 30 years before. The one-year survival rate, three-year survival rate, and five-year survival rate were 66.1%, 39.7%, and 32.5% respectively for the whole group, 93.5%, 70.1%, and 59.1% for the early stage patients, and 65.3%, 30.5%, and 23.5% respectively for the median stage patients. The half-year survival rate and one-year survival rate of the late stage patients were 52.5% and 14.7% respectively. Compared with the data 30 years before a lower percentages of the patients died of hepatic coma, hemorrhage of upper digestive tract and hemorrhage due to rupture of tumor, and a higher percentage of then died of asthenia universalis and other causes., Conclusion: In comparison with the situation 30 years ago, PLC can be diagnosed earlier. More patients undergo resection. The prognosis of PLC has been improved greatly.

Aim: To confirm if p53 mutation could be a routine predictive marker for the prognosis of hepatocellular carcinoma (HCC) patients., Methods: Two hundreds and forty-four formalin-fixed paraffin-embedded tumor samples of the patients with HCC receiving liver resection were detected for nuclear accumulation of p53. The percent of P53 immunoreactive tumor cells was scored as 0 to 3+ in P53 positive region (<10% -, 10-30% +, 31-50% ++, >50% +++). Proliferating cell nuclear antigen (PCNA) and some clinicopathological characteristics, including patients' sex, preoperative serum AFP level, tumor size, capsule, vascular invasion (both visual and microscopic), and Edmondson grade were also evaluated., Results: In univariate COX harzard regression model analysis, tumor size, capsule status, vascular invasion, and p53 expression were independent factors that were closely related to the overall survival (OS) rates of HCC patients. The survival rates of patients with 3+ for P53 expression were much lower than those with 2+ or + for P53 expression. Only vascular invasion (P<0.05) and capsule (P<0.01) were closely related to the disease-free survival (DFS) of HCC patients. In multivariate analysis, p53 overexpression (RI 0.5456, P<0.01) was the most significant factor associated with the OS rates of patients after HCC resection, while tumor size (RI 0.5209, P<0.01), vascular invasion (RI 0.5271, P<0.01) and capsule (RI-0.8691, P<0.01) were also related to the OS. However, only tumor capsular status was an independent predictive factor (P<0.05) for the DFS. No significant prognostic value was found in PCNA-LI, Edmondson's grade, patients' sex and preoperative serum AFP level., Conclusion: Accumulation of p53 expression, as well as tumor size, capsule and vascular invasion, could be valuable markers for predicting the prognosis of HCC patients after resection. The quantitative immunohistochemical scoring for P53 nuclear accumulation might be more valuable for predicting prognosis of patients after HCC resection than the common qualitative analysis.