Histopathological Response to Neoadjuvant Chemotherapy in Patients With Enneking Stage II Conventional Osteosarcoma of Extremities: A Retrospective-Single Institution Study in Vietnam.

BACKGROUND: The standard treatment for localized osteosarcoma is neoadjuvant chemotherapy before surgery, followed by adjuvant chemotherapy. Our aim was to report the rate of histopathological response to neoadjuvant chemotherapy for the treatment of extremity osteosarcoma in Vietnam. METHODS: We performed a retrospective study of stage II conventional osteosarcoma patients under 40 years-old who received MAP regimen as neoadjuvant chemotherapy at the Vietnam National Cancer Hospital between June 2019 and June 2022. Histopathological response was evaluated using the Huvos grading system, in which a good histopathological response was defined as a necrotic rate of 90% or more. RESULTS: Thirty-five eligible patients were included in the study. Male patients accounted for 65.7%, with a median age of 16 years (range, 8-38 years). Of the 35 cases, 31 were reported as stage IIB (88.6%). The femur and tibia were the most common sites in our study, accounting for 51.4% and 34.3%, respectively. The most common pathologic subtype was osteoblastic osteosarcoma (68.6%), followed by chondroblastic subtype (20%). After two cycles of MAP-regimen neoadjuvant chemotherapy, 28 of 35 patients (80%) underwent limb-sparing surgery. A good histopathological response was observed in 18 of 35 patients (51.4%). There were significant correlations between the duration of symptoms (P = 0.016), LDH (P = 0.001) serum levels at initial presentation, and ALP (P = 0.043) serum levels at initial presentation with histopathological response. CONCLUSION: This retrospective study suggests a possible association between symptom duration, pre-treatment LDH levels, and pre-treatment ALP levels with histopathological response rates. Additional clinical investigations with long-term follow-up are needed to investigate survival outcomes in the Asian population.

Clinical features and outcome of retinoblastoma at the Vietnam National Cancer Hospital.

OBJECTIVES: To characterize the clinical features, treatment, and outcome of children diagnosed with retinoblastoma (RB) at Vietnam National Cancer Hospital. METHODS: The study enrolled all RB patients newly diagnosed at Vietnam National Cancer Hospital from January 2018 to December 2022. The primary endpoint was overall survival (OS) and the eye salvage rate. RESULTS: In total, 139 patients were enrolled, 51.8% patients were male. Median age was 18.9 months. Most patients presented with leukocoria (63.3%), followed by strabismus (14.4%), and 43.9% had bilateral disease. Of 200 eyes, 129 (64.5%) were classified as group E. Extraocular extension was noted in 10 of 139 patients (7.2%). About one-third of the patients lived more than 300 kilometers (km) away from these hospitals, and 17.3% of the patients belonged to minority groups, both of which were dominated by group E and extraocular or high-risk eyes at the time of consultation. Primary enucleation was done for 57 eyes (28.5%), and 51 of 61 patients (83.6%) received eye salvage therapy in bilateral RB group. At study closure, 127 children were alive at the last follow-up, 12 cases were confirmed dead. The 5-year OS and progression-free survival (PFS) rates were 90.3% and 85.9%, respectively. In particular, ethnic minority, distance to hospital more than 150 km, and extraocular disease were significantly associated with higher mortality among children with RB treated in Vietnam National Cancer Hospital. CONCLUSIONS: There is a need to support for screening RB with early symptoms in grassroots medical facilities and raise awareness among patients' families through health education programs. Besides, caring and supporting treatment for patients from the ethnic minority and who live far from hospitals are also extremely necessary.

Stable Isotopes (δ13C and δ15N) and Trace Elements of Invertebrates and Fish from the Coastal Waters of Ha Tinh Province, Central Vietnam.

Stable isotope signatures (δ13C, δ15N) and trace elements (TEs) were analyzed from invertebrates and fish to assess food web structure and the biomagnification or biodilution of Cu, Pb, Cd, Zn, Mn, Cr, Hg and As in coastal waters of Ha Tinh Province, Central Vietnam. δ13C and δ15N values of purported food sources (sediments, phytoplankton, macroalgae, and zooplankton) ranged from -21.24 ± 0.39‰ to -16.72 ± 1.02‰ and from 3.02 ± 0.70‰ to 7.30 ± 0.42‰, respectively. The δ13C and δ15N values in invertebrates and fish ranged from -19.75 ± 0.10‰ to -18.68 ± 0.40‰, and from 7.02 ± 1.21‰ to 9.10 ± 0.29‰. The δ15N values showed that the food web structure could be divided into four trophic levels. The benthic invertebrates had significantly higher concentrations of Cu, Pb, Zn, Cd and As. Hg concentrations tended to accumulate higher in the crabs and fish. The biodilution of Pb, Cd, Zn, Cr was observed throughout the food web, whereas biomagnification was observed for Cr, Mn, and As in bivalves; Cd and Zn in gastropods; Pb, Cd, Zn, and As in crabs; Cd in prawns and Hg in fish.

Vitamin D intake and gastric cancer in Viet Nam: a case-control study.

BACKGROUND: Most recent laboratory studies have suggested a promising role of vitamin D and its analogs as novel chemotherapeutic agents for cancer treatment. However, epidemiological evidence, especially regarding the effects of vitamin D on gastric cancer is still inconsistent. OBJECTIVES: Our research aimed to evaluate the associations between vitamin D intake and the risk of developing gastric cancer through a case-control study in North Vietnam. METHODS: We accessed databases of the previous completed case-control studies to derive 1182 incident gastric cancer cases and 2995 hospital controls selected from hospitals in Hanoi from 2003 to 2019. Vitamin D intake was computed by multiplying the food frequency intake with nutrient content based on the Viet Nam Food Composition Tables. Data were collected through face-to-face interviews by trained interviewers using the validated semi-quantitative food frequency and demographic lifestyle questionnaires. The odds ratio and 95% confidence interval (OR and 95%CI) were estimated using unconditional logistic regression analysis. RESULTS: We observed a continual decline in gastric cancer risk according to the level-up of vitamin D intake in both genders, men, and women [Fifth vs. bottom quintile, OR, 95%CI: 0.68 (0.53, 0.86), OR, 95%CI: 0.72 (0.53, 0.97), OR, 95%CI: 0.58 (0.38, 0.89), respectively. Per increment quintile, the statistically significant decreased risk was seen by 7% in men and 13% in women. The significant inverse association between vitamin D intake remained in the subgroups of ever and never tobacco smoking; negative and positive H. pylori infection. CONCLUSION: The findings suggested that sufficient vitamin D intake was associated with a lower risk of Gastric Cancer in the Vietnamese population.

Anti-hypertensive effects of Callisia fragrans extract on Reno-vascular hypertensive rats.

OBJECTIVES: This study aims to investigate the anti-hypertensive effects of aqueous extract of Callisia fragrans and their underlying mechanism using a two-kidney one-clip (2K1C) model of reno-vascular hypertension in rats. METHODS: The reno-vascular hypertensive rats were treated with C. fragrans leaf extract (100 and 500 mg/kg; p.o.) and a reference drug, captopril (20 mg/kg; p.o.), for 4 weeks. The blood pressure and heart rate were recorded using a tail-cuff. The heart weight, left ventricular wall thickness, and serum creatinine and urea levels were measured. A spectrophotometric assay was used to analyze the angiotensin-converting enzyme (ACE) inhibition activity of the extract and the reference drug. The total volume and the concentration of sodium, potassium, and chloride in urine samples were evaluated. RESULTS: C. fragrans extract significantly reduced both systolic and diastolic blood pressures in the reno-vascular hypertensive rats. No significant difference in the heart rate was observed between each animal group. C. fragrans extract reduced the 2K1C-induced increase in the heart and body weight ratio and the left ventricular wall thickness. Moreover, the extract also attenuated the increase in serum urea induced by the 2K1C treatment. C. fragrans extract inhibited ACE activity in vitro with an IC50 of 20.97 ± 3.94 µg/ml. The urine output and urinary electrolyte excretion significantly increased in C. fragrans extract-treated rats. CONCLUSIONS: These findings demonstrated that C. fragrans extract can mitigate hypertension and alleviate ventricular hypertrophy and renal dysfunction in reno-vascular hypertensive rats, at least in part via ACE activity inhibition and diuretic property.

Investigation of an ALDH1A1-specific inhibitor for suppression of weight gain in a diet-induced mouse model of obesity.

BACKGROUND: Retinoic acid (RA) controls diverse physiological functions including weight regulation and energy metabolism. It has been reported that mice lacking ALDH1A1, one of the aldehyde dehydrogenases (ALDH) that synthesize RA, are healthy and resistant to weight gain, raising the possibility that inhibiting this enzyme might treat obesity. We previously demonstrated that treatment with a pan-ALDH1A enzyme inhibitor, WIN18446, suppressed weight gain in mice fed a high-fat diet (HFD), but caused increased hepatic lipidosis and reversible male infertility. METHODS: A series of piperazine compounds that inhibited ALDH1A1 were identified and their inhibitory activity was characterized in vitro using purified recombinant enzymes and cell-based assay systems. One potent compound, FSI-TN42 (N42) was examined for its oral bioavailability and pharmacodynamic effects. In addition, its effect on weight gain was investigated by daily oral administration to C57BL/6 male mice receiving a HFD, and compared with mice receiving WIN18446 or vehicle alone (n = 6/group, 200 mg compound/kg body weight) for 5 weeks. Body weights were measured weekly, and a glucose tolerance test was performed after 4 weeks of treatment. Tissues were collected to determine changes in adipose weight, hepatic lipidosis, retinoid metabolism, and expression of genes associated with RA and lipid metabolism. RESULTS: N42 irreversibly binds and inhibits ALDH1A1 in vitro with a low nM IC50 and 800-fold specificity for ALDH1A1 compared to ALDH1A2. Daily oral administration of N42 significantly suppressed weight gain (P < 0.05) and reduced visceral adiposity (p < 0.05) in mice fed a HFD without the hepatic lipidosis observed with WIN18446 treatment. CONCLUSIONS: We developed a potent and specific inhibitor of ALDH1A1 that suppressed weight gain in mice fed a HFD. These findings demonstrate that inhibition of ALDH1A1 is a feasible target for drug development to treat and/or prevent obesity.

Fine root production in a chronosequence of mature reforested mangroves.

Mangroves are among the world's most carbon-dense ecosystems, but have suffered extensive deforestation, prompting reforestation projects. The effects of mangrove reforestation on belowground carbon dynamics are poorly understood. In particular, we do not know how fine root production develops following mangrove reforestation, despite fine root production being a major carbon sink and an important control of mangrove soil accretion. Using minirhizotrons, we investigated fine root production and its depth variation along a chronosequence of mature Vietnamese mangroves. Our results showed that fine root production decreases strongly with stand age in the uppermost 32 cm of our soil profiles. In younger mangrove stands, fine root production declines with depth, possibly due to a vertical gradient in soil nutrient availability; while root production in the oldest stand is low at all depths and exhibits no clear vertical pattern. A major fraction of fine root production occurs deeper than 30 cm, depths that are commonly omitted from calculations of mangrove carbon budgets. Younger mangroves may accrue shallow soil organic matter faster than older mangroves. Therefore, root productivity and forest stand age should be accounted for when forecasting mangrove carbon budgets and resistance to sea-level rise.

Timeliness of contact tracing among flight passengers during the COVID-19 epidemic in Vietnam.

BACKGROUND: International air travel plays an important role in the global spread of SARS-CoV-2, and tracing of close contacts is an integral part of the public health response to COVID-19. We aimed to assess the timeliness of contact tracing among airline passengers arriving in Vietnam on flights containing COVID-19 cases and investigated factors associated with timeliness of contact tracing. METHODS: We included data from 2228 passengers on 22 incoming flights between 2 and 19 March 2020. Contact tracing duration was assessed separately for the time between the date of index case confirmation and date of contact tracing initiation (interval I), and the date of contact tracing initiation and completion (interval II). We used log-rank tests and multivariable Poisson regression models to identify factors associated with timeliness. RESULTS: The median duration of interval I and interval II was one (IQR: 1-2) and 3 days (IQR: 2-5), respectively. The contact tracing duration was shorter for passengers from flights where the index case was identified through mandatory testing directly upon arrival (median = 4; IQR: 3-5) compared to flights with index case detection through self-presentation at health facilities after arrival (median = 7; IQR: 5-8) (p-value = 0.018). Cumulative hazards for successful tracing were higher for Vietnamese nationals compared to non-Vietnamese nationals (p < 0.001). CONCLUSIONS: Contact tracing among flight passengers in the early stage of the COVID-19 epidemic in Vietnam was timely though delays occurred on high workload days. Mandatory SARS-CoV-2 testing at arrival may reduce contact tracing duration and should be considered as an integrated screening tool for flight passengers from high-risk areas when entering low-transmission settings with limited contact tracing capacity. We recommend a standardized risk-based contact tracing approach for flight passengers during the ongoing COVID-19 epidemic.

Utilization of Response Surface Methodology in Optimization of Polysaccharides Extraction from Vietnamese Red Ganoderma lucidum by Ultrasound-Assisted Enzymatic Method and Examination of Bioactivities of the Extract.

Red Ganoderma lucidum (G. lucidum) is a popular medicinal herb commonly used in Vietnamese traditional remedies due to its potential value for health. In this study, polysaccharides were extracted from G. lucidum using ultrasound-assisted enzymatic extraction method. The response surface methodology and Box-Behnken design were employed to investigate the effects of pH, extraction temperature, extraction time, and ultrasonic power on the content of polysaccharides. Based on ultraviolet-visible spectroscopy analysis, the highest content of polysaccharides in the extract was 32.08 mg/g under optimum experimental parameters including enzyme concentration of 3%, pH of 5.5, extraction temperature of 45°C, extraction time of 30 min, and ultrasonic power of 480 W. The Fourier-transform infrared spectroscopy was also used to identify the functional groups in the extracts. The molecular weights of polysaccharides were determined by gel permeation chromatography. The obtained extract was then evaluated for anticancer activities by using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, showing the anticancer activities with the half-maximal inhibitory concentration value of more than 512 µg/mL. This result suggested that UAEE could be considered as an appropriate and effective extraction method for bioactive crude polysaccharides from G. lucidum.

Sensitivity of mangrove soil organic matter decay to warming and sea level change.

Mangroves are among the world's most carbon-dense ecosystems, but they are threatened by rapid climate change and rising sea levels. The accumulation and decomposition of soil organic matter (SOM) are closely tied to mangroves' carbon sink functions and resistance to rising sea levels. However, few studies have investigated the response of mangrove SOM dynamics to likely future environmental conditions. We quantified how mangrove SOM decay is affected by predicted global warming (+4°C), sea level changes (simulated by altering of the inundation duration to 0, 2, and 6 hr/day), and their interaction. Whilst changes in inundation duration between 2 and 6 hr/day did not affect SOM decay, the treatment without inundation led to a 60% increase. A warming of 4°C caused SOM decay to increase by 21%, but longer inundation moderated this temperature-driven increase. Our results indicate that (a) sea level rise is unlikely to decrease the SOM decay rate, suggesting that previous mangrove elevation gain, which has allowed mangroves to persist in areas of sea level rise, might result from changes in root production and/or mineral sedimentation; (b) sea level fall events, predicted to double in frequency and area, will cause periods of intensified SOM decay; (c) changing tidal regimes in mangroves due to sea level rise might attenuate increases in SOM decay caused by global warming. Our results have important implications for forecasting mangrove carbon dynamics and the persistence of mangroves and other coastal wetlands under future scenarios of climate change.

Detecting and Quantifying Microscale Chemical Reactions in Pharmaceutical Tablets by Stimulated Raman Scattering Microscopy.

It has been estimated that approximately 50% of all marketed drug molecules are manufactured and administered in the form of salts, often with the goal of improving solubility, dissolution rate, and efficacy of the drug. However, salt disproportionation during processing or storage is a common adverse effect in these formulations. Due to the heterogeneous nature of solid drug formulations, it is essential to characterize the drug substances noninvasively at micrometer resolution to understand the molecular mechanism of salt disproportionation. However, there is a lack of such capability with current characterization methods. In this study, we demonstrate that stimulated Raman scattering (SRS) microscopy can be used to provide sensitive and quantitative chemical imaging of the salt disproportionation reaction of pioglitazone hydrochloride (PIO-HCl) at a very low drug loading (1% w/w). Our findings illuminate a water mediated pathway of drug disproportionation and highlight the importance of noninvasive chemical imaging in a mechanistic study of solid-state chemical reactions.

In Situ Stimulated Raman Scattering (SRS) Microscopy Study of the Dissolution of Sustained-Release Implant Formulation.

Localized drug delivery systems (DDSs) provide therapeutic levels of drug agent while mitigating side effects of systemic delivery. These systems offer controlled release over extended periods of time making them attractive therapies. Monitoring drug dissolution is vital for developing safe and effective means of drug delivery. Currently, dissolution characterization methods are limited to bulk analysis and cannot provide dissolution kinetics at high spatial resolution. However, dissolution rates of drug particles can be heterogeneous with influences from many factors. Insights into finer spatiotemporal dynamics of single particle dissolution could potentially improve pharmacokinetic modeling of dissolution for future drug development. In this work, we demonstrate high-resolution chemical mapping of entecavir, a hepatitis B antiviral drug, embedded in a slow release poly(d,l-lactic acid) formulation with stimulated Raman scattering (SRS) microscopy. By tracking the volume change of individual micron-sized drug particles within the polymer matrix, we establish an analytical protocol for quantitatively profiling dissolution of single crystalline particles in implant formulations in an in situ manner.

A New Technique in Alveolar Cleft Bone Grafting for Dental Implant Placement in Patients With Cleft Lip and Palate.

OBJECTIVE: To evaluate 2 iliac corticocancellous-block grafting techniques for dental implant placement in residual alveolar clefts. DESIGN: Nonrandomized prospective clinical trial between March 2010 and December 2014. SETTING: National Hospital of Odonto-Stomatology, Hanoi, Vietnam. PARTICIPANTS: Thirty-two patients (23 female, 9 male; mean age, 21.28 years; range, 16-31 years) with unilateral complete alveolar cleft after reconstructive surgery for cleft lip and palate (CLP). INTERVENTIONS: Harvested iliac crest bone was cut into 2 corticocancellous blocks. The smaller block was adapted against the sutured nasal mucoperiosteum and overlaid with cancellous bone; the larger one overlapped the labial cleft margin and was fixed with screws. Endosteal dental implants were placed after 4 to 6 months, and final restorations were delivered 6 months later. MAIN OUTCOME MEASURES: Flap statuses were assessed clinically. Bone formation was assessed using the Enemark scale. Cone-beam computed tomography was used for graft height and width measurements. Implant health was assessed by the Misch criteria. RESULTS: The mean postgrafting follow-up period was 36.7 ± 10.4 (range, 18-53) months. Three patients (9.4%) showed flap dehiscence but no infection 7 days after bone grafting. Twenty-nine patients (90.6%) had 75% to 100% bone fill (Enemark score of 1). The mean graft height and width were 11.4 ± 2.4 and 6.1 ± 1.0 mm, respectively. Sufficient bone for implant placement was noted in 29 patients (90.6%); the others required partially fixed prostheses. All implants functioned for at least 18 months. CONCLUSION: The proposed technique is reliable to reconstruct the alveolar cleft for implant placement in CLP patients.

Anti-Angiogenic Tyrosine Kinase Inhibitor-Related Toxicities Among Cancer Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Targeting of angiogenesis has become a major therapeutic approach for the treatment of various advanced cancers. There are many unresolved questions on the toxicity of anti-angiogenic tyrosine kinase inhibitors (TKIs). OBJECTIVE: We performed a meta-analysis to assess the toxicity prevalence of the different anti-angiogenic TKIs among cancer patients and in subpopulations of interest including patients with renal cell carcinoma. PATIENTS AND METHODS: We searched the MEDLINE and Cochrane Library databases to November 2023. Clinical trials were eligible if they set out to report the grade ≥3 toxicities related to one of the seven currently approved anti-angiogenic TKIs as monotherapies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method was applied with PROSPERO (CRD42023411946). RESULTS: The 421 eligible studies included a total of 56,895 cancer patients treated with anti-angiogenic TKI monotherapy. Twenty-four different cancer types were identified, mainly renal cell carcinoma (41.9% of the patients). The anti-angiogenic TKI was sorafenib (34.5% of the patients), sunitinib (30.5%), regorafenib (10.7%), pazopanib (9.4%), cabozantinib (7.7%), axitinib (4.3%), and lenvatinib (2.9%). The pooled prevalence of grade 3 and 4 toxicities was 56.1% (95% confidence interval 53.5-58.6), with marked between-study heterogeneity (I2 = 96.8%). Toxicity profiles varied considerably depending on the type of TKI, the cancer type, and the specific patient characteristics. In particular, Asian patients and elderly people had higher prevalences of severe toxicities, with pazopanib being the best-tolerated drug. For patients treated with sunitinib, particularly those with metastatic RCC, there was no significant difference in terms of toxicity according to the regimen schedule. CONCLUSIONS: This meta-analysis highlights the toxicity profiles of anti-angiogenic TKI monotherapies, and thus enables high-level recommendations for the choice of anti-angiogenic TKIs on the basis of the patient's age, ethnicity, comorbidities, and comedications, for personalized treatment.

Molecular detection and association of 12.1 kb deletion within the high mobility AT-hook 2 gene in the Netherlands dwarf rabbit (Oryctolagus Cuniculus).

Rabbits are mainly bred for human consumption and medical research. However, it has been recently showed that several rabbit breeds are also kept as pets for human leisure. The Netherlands dwarf rabbit is currently in the immense interest of many Vietnamese customers due to its personality and miniature stature. However, 12.1 kb deletion from position 44,709,089 to 44,721,236 bp in the high mobility AT-hook 2 (HMGA2) gene on chromosome 4 was identified as the structural variant causing dwarfism and altered craniofacial development in this breed. It has been documented that HMGA2 plays an important role in regulating growth and individuals with genotype HMGA2 del/del are fatal several days after birth. Despite the economically high value of the Netherlands dwarf rabbit, there has been no study on the genetic survey of lethal alleles in this breed in Vietnam. The aim of this study is to develop a fast and reliable method to screen the frequency of lethal alleles of HMGA2 in the South of Vietnam. Rabbit saliva was collected, and DNA extraction was followed. Multiplex polymerase chain reaction (PCR) with three primers was optimized and performed to detect the presence of 12.1 kb deletion within the HMGA2 sequence. Our data showed that the 12.1 kb deletion in the Netherlands dwarf rabbit population was detected by our optimized multiplex PCR. In 100 rabbit animals, 34 and 16 individuals were homozygous wild type (+/+) and homozygous mutant (del/del), respectively, while 50 rabbits were heterozygous. The frequency of HMGA2 lethal allele carrier was 66% (66/100 individuals). Our results indicated that we successfully developed a fast, accurate multiplex PCR to detect carrier individuals. Verification of the genotypes was followed by sequencing. We recommend implementing our multiplex PCR procedure in genetic selection for carrier and homozygous wild-type animals in the mating scheme to prevent the lethality of the rabbit offspring. Additionally, awareness should be raised among rabbit breeders to monitor the genetic makeup of the Netherlands dwarf rabbit populations. However, due to the limitation of the sample size, more samples should be taken in future studies to obtain the genetic frequency of the HMGA2 lethal allele more accurately.

Clinical and Paraclinical Features, Outcome, and Prognosis of Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: A Retrospective Study of 31 Vietnamese Patients.

Background: Extranodal natural killer (NK)/T-cell lymphoma, nasal type is a rare, aggressive, and poor prognostic subtype. The concurrent chemoradiotherapy followed by chemotherapy showed a relatively high response rate and the toxicity due to the treatment is acceptable. The study attempted to report the clinicopathological features, the survival outcome, and response rates of stages I-II, nasal type ENKTL patients treated with CCRT followed by adjuvant VIPD chemotherapy in Vietnam. Materials and Methods: The current study was conducted on 31 stage I or II NK/T cell lymphoma, nasal-type patients received by CCRT, followed by adjuvant VIPD chemotherapy. Information on patient demographics, disease stage, clinical symptoms, tumor, and paraclinical characteristics were collected. The primary endpoints of this study were OS and response rates. Results: After CCRT, 26 out of 31 (83.9%) patients had stable disease or response. Overall response rate (ORR) was observed in 80.6% of patients with a complete response rate of 67.7%. Low-risk PINK patients had a higher response rate than the intermediate- risk group (p=0.038). Mean disease-free survival was 44.3±4.5 months (95% CI, 35.4-53.1 months). Mean overall survival was 46.8±4.5 months (95% CI, 37.99-55.8 months). The intermediate-risk PINK patients had a significantly lower OS rate than low-risk patients. Conclusion: Concurrent chemoradiotherapy followed by adjuvant VIPD chemotherapy showed a high response rate and survival benefit in stages I-II, nasal type, and extranodal natural killer (NK)/T-cell lymphoma Vietnamese patients.

Kaempferol-3-O-(2″-O-galloyl-ß-D-glucopyranoside): a novel neuroprotective agent from Diospryros kaki against cerebral ischemia-induced brain injury.

Our previous study demonstrated neuroprotective and therapeutic effects of a standardized flavonoid extract from leaves of Diospyros kaki L.f. (DK) on middle cerebral artery occlusion-and-reperfusion (MCAO/R)-induced brain injury and its underlying mechanisms. This study aimed to clarify flavonoid components responsible for the effects of DK using in vitro and in vivo transient brain ischemic models. Organotypic hippocampal slice cultures (OHSCs) subjected to oxygen- and glucose-deprivation (OGD) were performed to evaluate in vitro neuroprotective activity of DK extract and nine isolated flavonoid components. MCAO/R mice were employed to elucidate in vivo neuroprotective effects of the flavonoid component that exhibited the most potent neuroprotective effect in OHSCs. DK extract and seven flavonoids [quercetin, isoquercetin, hyperoside, quercetin-3-O-(2″-O-galloyl-ß-D-galactopyranoside), kaempferol, astragalin, and kaempferol-3-O-(2″-O-galloyl-ß-D-glucopyranoside) compound (9)] attenuated OGD-induced neuronal cell damage and compound (9) possessed the most potent neuroprotective activity in OHSCs. The MCAO/R mice showed cerebral infarction, massive weight loss, characteristic neurological symptoms, and deterioration of neuronal cells in the brain. Compound (9) and a reference drugs, edaravone, significantly attenuated these physical and neurological impairments. Compound (9) mitigated the blood-brain barrier dysfunction and the change of glutathione and malondialdehyde content in the MCAO mouse brain. Edaravone suppressed the oxidative stress but did not significantly affect the blood-brain barrier permeability. The present results indicated that compound (9) is a flavonoid constituent of DK with a potent neuroprotective activity against transient ischemia-induced brain damage and this action, at least in part, via preservation of blood-brain barrier integrity and suppression of oxidative stress caused by ischemic insult.

Time of day differences in the regulation of glutathione levels in the rat lens.

Introduction: Evidence in non-ocular tissues indicate that the antioxidant glutathione (GSH) may be regulated in a circadian manner leading to the idea that GSH levels in the lens may also be controlled in a circadian manner to anticipate periods of oxidative stress. Methods: Male rat Wistar lenses (6 weeks) were collected every 4 hours over a 24-hour period at 6am, 10am, 2pm, 6pm, 10pm and 2am and quantitative-PCR, western blotting and immunohistochemistry performed to examine the expression of core clock genes and proteins (BMAL1, CLOCK, CRY1-2, PER 1-3) and their subcellular localisation over a 24-hour period. Western blotting of lenses was also performed to examine the expression of NRF2, a transcription factor involved in regulating genes involved in GSH homeostasis and GSH related enzymes (GCLC, GS and GR) over the 24-hour period. Finally, HLPC was used to measure GSH levels in the aqueous humour and lenses every 4 hours over a 24-hour period. Results: The rat lens contains the core molecular components of a circadian clock with the expression of core clock proteins, NRF2 and GSH related enzymes fluctuating over a 24-hour period. BMAL1 expression was highest during the day, with BMAL1 localised to the nuclei at 10am. NRF2 expression remained constant over the 24-hour period, although appeared to move in and out of the nuclei every 4 hours. GSH related enzyme expression tended to peak at the start of night which correlated with high levels of GSH in the lens and lower levels of GSH in the aqueous humour. Conclusion: The lens contains the key components of a circadian clock, and time-of-day differences exist in the expression of GSH and GSH related enzymes involved in maintaining GSH homeostasis. GSH levels in the rat lens were highest at the start of night which represents the active phase of the rat when high GSH levels may be required to counteract oxidative stress induced by cellular metabolism. Future work to directly link the clock to regulation of GSH levels in the lens will be important in determining whether the clock can be used to help restore GSH levels in the lens.

IOTA simple rules: An efficient tool for evaluation of ovarian tumors by non-experienced but trained examiners - A prospective study.

Objectives: A simple and efficient tool for evaluating ovarian tumors in general hospitals where radiologists without experience in gynecological ultrasound is necessary. This study aims to evaluate the diagnostic performance of IOTA simple rules in initial classification of ovarian tumors by non-experienced examiners who have received simple training. Materials and method: A prospective single-center study was conducted at Hanoi Obstetrics and Gynecology Hospital. Three resident gynecologists trained themselves for two weeks and then received hands-on practice under the supervision of experts for another two weeks. The examiners performed ultrasound on 424 eligible women scheduled for surgery for ovarian tumors and classified the tumors based on IOTA simple rules. The postoperative pathology of ovarian tumors was used as the gold standard. Results: 90.8 % (385/424) of the tumors were benign. Simple rules were applicable in 399/424 (94.1 %) tumors, with a sensitivity of 84.8 % (95 % CI, 70.2-94.3), specificity of 98.9 % (95 % CI, 97.5-99.7), positive predictive value of 87.5 % (95 % CI, 73.3-95.9), and negative predictive value of 98.6 % (95 % CI, 97.1-99.5). The sensitivity of IOTA simple rules was higher in postmenopausal women (91.7 % vs. 81.0 %), while the specificity was higher in premenopausal women (99.4 % vs. 95.8 %). Accuracy was 100 % in all ten pregnant women were assessed using these rules. Conclusion: In conclusion, in the hands of non-expert examiners who were trained thoroughly, IOTA simple rules are a simple and efficient tool for clinical practice in centers where expert radiologists in gynecology are not always available. The training program is simple and could be applied widely in other clinical centers. Further studies are necessary to evaluate the effectiveness of the IOTA simple rules in assessing ovarian tumors among pregnant women.

Bacopa monnieri ameliorates memory deficits in olfactory bulbectomized mice: possible involvement of glutamatergic and cholinergic systems.

This study investigated the effects of alcoholic extract of Bacopa monnieri (L.) Wettst. (BM) on cognitive deficits using olfactory bulbectomized (OBX) mice and the underlying molecular mechanisms of its action. OBX mice were treated daily with BM (50 mg/kg, p.o.) or a reference drug, tacrine (2.5 mg/kg, i.p.), 1 week before and continuously 3 days after OBX. Cognitive performance of the animals was analyzed by the novel object recognition test, modified Y maze test, and fear conditioning test. Brain tissues of OBX animals were used for neurochemical and immunohistochemical studies. OBX impaired non-spatial short-term memory, spatial working memory, and long-term fair memory. BM administration ameliorated these memory disturbances. The effect of BM on short-term memory deficits was abolished by a muscarinic receptor antagonist, scopolamine. OBX downregulated phosphorylation of synaptic plasticity-related signaling proteins: NR1 subunit of N-methyl-D-aspartate receptor, glutamate receptor 1 (GluR1), and calmodulin-dependent kinase II but not cyclic AMP-responsive element binding protein (CREB), and reduced brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. OBX also reduced choline acetyltransferase in the hippocampus and cholinergic neurons in the medial septum, and enlarged the size of lateral ventricle. BM administration reversed these OBX-induced neurochemical and histological alterations, except the decrease of GluR1 phosphorylation, and enhanced CREB phosphorylation. Moreover, BM treatment inhibited ex vivo activity of acetylcholinesterase in the brain. These results indicate that BM treatment ameliorates OBX-induced cognition dysfunction via a mechanism involving enhancement of synaptic plasticity-related signaling and BDNF transcription and protection of cholinergic systems from OBX-induced neuronal damage.