Assessment of physicochemical properties and radioactivity in groundwater at households living in bac Lieu province, vietnam.

This paper presents findings on groundwater physiochemical composition and radioactivity levels in households in Bac Lieu province, Vietnam. Through discriminant analysis, it was observed that groundwater quality exhibits spatial variations corresponding to saline intrusion zones. The paired-samples T-tests revealed significantly different ratios of Ra-224, Ra-226, and Ra-228 isotopes between Na-Cl and Ca-Na-HCO3 water types. All three water types had a ratio of Ra-226/Ra-228 of approximately one, indicating the presence of groundwater aquifers beneath the crust and fluvial marine sediment. Furthermore, strong associations between sulfate and calcium suggest that CO2 enrichment in groundwater aquifers indicates anoxic aquatic environments. Twenty-five of the thirty-three evaluated samples exceeded the national technical regulations for domestic water quality with parameters such as chloride, sulfate, sodium, gross alpha, or total dissolved solids. Fifteen samples exceeded gross alpha's allowable contamination threshold of 0.1 Bq/L. The combination of Ra-226 and Ra-228 did not surpass the U.S. Environmental Protection Agency's recommended limit of 0.185 Bq/L. However, nineteen samples exhibited annual committed effective doses of radium isotopes for infants that exceeded the WHO recommendation of 0.1 mSv/year.

DeepSomatic: Accurate somatic small variant discovery for multiple sequencing technologies.

Somatic variant detection is an integral part of cancer genomics analysis. While most methods have focused on short-read sequencing, long-read technologies now offer potential advantages in terms of repeat mapping and variant phasing. We present DeepSomatic, a deep learning method for detecting somatic SNVs and insertions and deletions (indels) from both short-read and long-read data, with modes for whole-genome and exome sequencing, and able to run on tumor-normal, tumor-only, and with FFPE-prepared samples. To help address the dearth of publicly available training and benchmarking data for somatic variant detection, we generated and make openly available a dataset of five matched tumor-normal cell line pairs sequenced with Illumina, PacBio HiFi, and Oxford Nanopore Technologies, along with benchmark variant sets. Across samples and technologies (short-read and long-read), DeepSomatic consistently outperforms existing callers, particularly for indels.

A patient-derived cell model for malignant transformation in IDH-mutant glioma.

Malignant transformation (MT) is commonly seen in IDH-mutant gliomas. There has been a growing research interest in revealing its underlying mechanisms and intervening prior to MT at the early stages of the transforming process. Here we established a unique pair of matched 3D cell models: 403L, derived from a low-grade glioma (LGG), and 403H, derived from a high-grade glioma (HGG), by utilizing IDH-mutant astrocytoma samples from the same patient when the tumor was diagnosed as WHO grade 2 (tumor mutational burden (TMB) of 3.96/Mb) and later as grade 4 (TMB of 70.07/Mb), respectively. Both cell models were authenticated to a patient's sample retaining endogenous expression of IDH1 R132H. DNA methylation profiles of the parental tumors referred to LGG and HGG IDH-mutant glioma clusters. The immunopositivity of SOX2, NESTIN, GFAP, OLIG2, and beta 3-Tubulin suggested the multilineage potential of both models. 403H was more prompt to cell invasion and developed infiltrative HGG in vivo. The differentially expressed genes (DEGs) from the RNA sequencing analysis revealed the tumor invasion and aggressiveness related genes exclusively upregulated in the 403H model. Pathway analysis showcased an enrichment of genes associated with epithelial-mesenchymal transition (EMT) and Notch signaling pathways in 403H and 403L, respectively. Mass spectrometry-based targeted metabolomics and hyperpolarized (HP) 1-13C pyruvate in-cell NMR analyses demonstrated significant alterations in the TCA cycle and fatty acid metabolism. Citrate, glutamine, and 2-HG levels were significantly higher in 403H. To our knowledge, this is the first report describing the development of a matched pair of 3D patient-derived cell models representative of MT and temozolomide (TMZ)-induced hypermutator phenotype (HMP) in IDH-mutant glioma, providing insights into genetic and metabolic changes during MT/HMP. This novel in vitro model allows further investigation of the mechanisms of MT at the cellular level.

Serial tissue expansion and excision for reconstruction of giant dorsal congenital melanocytic nevus: A case report.

Giant congenital melanocytic nevus often necessitates meticulous planning and multiple treatment stages for complete surgical excision. This report presents a case of giant congenital melanocytic nevus on the back managed through serial tissue expansion and excision. Initially, two expanders were placed at the deep fascia level. Sequential outpatient expansions over 10 weeks were followed by expander removal, partial nevus excision, defect coverage with expanded skin flaps, and simultaneous placement of a new expander. The subsequent single expander expansion over 12 weeks involved a total of 600 mL of saline. After three operations spanning approximately 6 months, 54 cm × 36 cm of giant congenital melanocytic nevus skin, covering 65% of the patient's back, was completely excised. Serial tissue expansion and excision may be an effective surgical approach for managing dorsal giant congenital melanocytic nevus, reducing the need for multiple surgeries and achieving favorable aesthetic outcomes.

Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease.

Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus. In a murine GVHD model aggravated by carbapenem antibiotics, introducing B. ovatus reduced GVHD severity and improved survival. These beneficial effects of Bacteroides ovatus were linked to its ability to metabolize dietary polysaccharides into monosaccharides, which suppressed the mucus-degrading capabilities of colonic mucus degraders such as Bacteroides thetaiotaomicron and Akkermansia muciniphila, thus reducing GVHD-related mortality. Collectively, these findings reveal the importance of microbiota in aLGI-GVHD and therapeutic potential of B. ovatus.

Temporal Trends in Tobacco Smoking Prevalence During the Period 2010-2020 in Vietnam: A Repeated Cross-Sectional Study.

Objectives: This study used repeated cross-sectional data from three national surveys in Vietnam to determine tobacco smoking prevalence from 2010 to 2020 and disparities among demographic and socioeconomic groups. Methods: Tobacco smoking temporal trends were estimated for individuals aged 15 and over and stratified by demographic and socioeconomic status (SES). Prevalence estimates used survey weights and 95% confidence intervals. Logistic regression models adjusted for survey sample characteristics across time were used to examine trends. Results: Tobacco smoking prevalence dropped from 23.8% in 2010 to 22.5% in 2015 and 20.8% in 2020. The adjusted OR for 2015 compared to 2010 was 0.87, and for 2020 compared to 2010 was 0.69. Smoking decreased less for employed individuals than unemployed individuals in 2020 compared to 2010. Smoking was higher in the lower SES group in all 3 years. Higher-SES households have seen a decade-long drop in tobacco use. Conclusion: This prevalence remained constant in lower SES households. This highlights the need for targeted interventions to address the specific challenges faced by lower-SES smokers and emphasizes the importance of further research to inform effective policies.

Estimating eGFR using serum creatinine or cystatin C in healthy Vietnamese population.

Very few studies worldwide have assessed the estimated glomerular filtration rate (eGFR) using serum cystatin C (ScysC) in comparison to the gold standard measured glomerular filtration rate (mGFR) with a gamma camera technique using 99m-Technetium-Diethylene Triaminepentoacetic Acid (99mTc-DTPA). To determine the eGFR formula with the most accurate estimate of glomerular filtration rate when compared with mGFR in a healthy population in Vietnam. We conducted a cross-sectional descriptive study of more than 100 adults without hypertension. The study subjects were examined for general characteristics and blood biochemistry tests to assess eGFR, and the glomerular filtration rate was measured using 99mTc-DTPA with the Gates technique to record mGFR. The estimated values of the eGFR formula were evaluated and compared with the actual mGFR using 99mTechnetium-DTPA. Serum creatinine (Scr) concentration showed a significant difference between males and females: 0.9 ±â€…0.1 versus 0.8 ±â€…0.1 (P < .001), while ScysC concentration did not show this difference. The mGFR in the age groups < 40, 40 to 59, and ≥ 60: 105.0 ±â€…9.9, 94.8 ±â€…8.6, and 93.4 ±â€…10.6, respectively (P < .001). The eGFR-CKD-EPI-cystatin C 2012 formula showed the highest positive correlation with mGFR (ΔGFR = -1.6, R = 0.68, P < .001). eGFR calculated using cystatin C does not require sex adjustment, whereas, for creatinine, sex adjustment is necessary. The eGFR-CKD-Epi-CysC formula showed the lowest difference and a strong correlation with mGFR.

Simultaneous versus sequential fractional CO2 laser and subcision combination for management of post-acne atrophic scars: A split-face comparative study.

BACKGROUND: A combination of fractional CO2 laser and subcision is usually employed for the treatment of post-acne atrophic scars. However, the efficacy and safety of both simultaneous and sequential combination therapies should be explored. AIMS: To compare the efficacy and safety of simultaneous and sequential fractional CO2 laser and subcision combination therapies for post-acne atrophic scars. PATIENTS AND METHODS: This single-blind, split-face clinical trial included 34 patients with post-acne atrophic scars at our institution. Each patient underwent three sessions of subcision combined with fractional CO2 laser, with a 1-month interval between each session. The left side of the face was treated with simultaneous combination therapy, whereas the right side was treated with sequential combination therapy. Treatment efficacy was assessed at 4, 8, and 12 weeks; and 3 and 6 months after the last session. RESULTS: Simultaneous and sequential treatments demonstrated comparable efficacy. Regarding the adverse events, the side of the face undergoing simultaneous treatment experienced longer swelling duration, higher pain levels during laser treatment, and shorter downtime. CONCLUSIONS: Despite the longer swelling time and higher pain levels during laser treatment in the simultaneous treatment side, the effectiveness and satisfaction level of the CO2 fractional laser and subcision for treatment of the acne scars were comparable between the two combinations, with a shorter downtime for the simultaneous than for the sequential combination therapy.

Spatio-temporal characterization of drought variability in data-scarce regions using global precipitation data: a case study in Cauto river basin, Cuba.

Drought is considered the most severe water-related disaster in the Cauto river basin, which is the longest river and the main agricultural producer in Cuba. Better understanding of drought characteristics is crucial to drought management. Given the sparsity of ground-based precipitation observations in the Cauto, this study aims at using gridded global precipitation to analyze the spatio-temporal variations of drought in this river basin. Firstly, the monthly Climate Hazards Group InfraRed Precipitation with Station data (CHIRPS) was calibrated with the gauged precipitation using the Thiessen polygon-based method and linear least squares regression equations. Then, the gridded standardized precipitation index (SPI) with time scales of 3, 6, 9 months and drought characteristics, namely, drought frequency, duration and intensity were calculated using the calibrated CHIRPS. Finally, the spatio-temporal analysis was performed to investigate the variations of drought in the Cauto river basin in time and space. The obtained results show that the calibrated CHIRPS is highly consistent with the gauged observations and is capable of determining the magnitude, time, and spatial extent of drought events in the Cauto river basin. The trend analysis by the Mann-Kendall test reveals that although the trend is not statistically significant, the SPI tends to decrease with time in the dry season, which indicates the more severe drought. The spatial analysis indicates that the lower altitude area of the Cauto river basin is suffered from longer drought duration and higher drought intensity than the upper one. This study expresses the importance of open global precipitation data sources in monitoring and quantifying drought characteristics in data-scarce regions.

Optimization of leucomalachite green degradation through electron beam and persulfate oxidation using box-behnken design and life cycle assessment.

This study explored the treatment of Leucomalachite Green (LMG) solutions using an electron beam and sodium persulfate (Na2S2O8), employing Box-Behnken design (BBD) to optimize operational variables such as absorbed dose, initial pH and Na2S2O8 concentration. The findings highlighted an optimal absorbed dose of 4.5 kGy, a Na2S2O8 concentration of 1.0 mM, and an initial pH of 6, leading to a remarkable 97.77% removal of LMG. The adjusted R2 for the model indicated a close match of 1.4% between predicted and actual outcomes under these optimized conditions, affirming the quadratic model's suitability for predicting the LMG removal process using combined EB and Na2S2O8. To assess the environmental impact of the LMG treatment, the study applied SimaPro 9.4 with the TRACI tool, examining ten distinct environmental impact categories. The results unveiled that deionized water and Na2S2O8 exhibited a notable impact on global warming (GW) and ecotoxicity (ET) in controlled laboratory settings. Furthermore, a comparative analysis of four scenarios shed light on the environmental implications of different energy sources. Notably, electricity generated from waste incineration demonstrated a substantial influence on all environmental indicators. In contrast, natural gas emerged as the cleanest source for electricity generation, offering a promising avenue for reducing environmental impacts. This study presents a practical method for addressing dye contaminants through the employment of EB in conjunction with Na2S2O8, with potential implications for broader applications.

Effect of Bile on Hemodynamics and Blood Micro-Rheological Parameters in Experimental Models of Bilhemia.

As a rare complication of liver injury and certain interventions, bile can enter the bloodstream depending on the pressure gradient, resulting in bilhemia. Its micro-rheological and hemodynamic effects are still unclear. We aimed to study these parameters in experimental bilhemia models. Under general anesthesia, via laparotomy, bile was obtained by gallbladder puncture from pigs and by choledochal duct cannulation from rats. In vitro, 1 µL and 5 µL of bile were mixed with 500 µL of anticoagulated autologous blood. The systemic effect was also assessed (i.v. bile, 200 µL/bwkg). Hemodynamic and hematological parameters were monitored, and red blood cell (RBC) deformability and aggregation were determined. RBC deformability significantly decreased with the increasing bile concentration in vitro (1 µL: p = 0.033; 5 µL: p < 0.001) in both species. The RBC aggregation index values were concomitantly worsened (1 µL: p < 0.001; 5 µL: p < 0.001). The mean arterial pressure and heart rate decreased by 15.2 ± 6.9% and 4.6 ± 2.1% in rats (in 10.6 ± 2.6 s) and by 32.1 ± 14% and 25.2 ± 11.63% in pigs (in 48.3 ± 18.9 s). Restoration of the values was observed in 45 ± 9.5 s (rats) and 130 ± 20 s (pigs). Bilhemia directly affected the hemodynamic parameters and caused micro-rheological deterioration. The magnitude and dynamics of the changes were different for the two species.

Severus: accurate detection and characterization of somatic structural variation in tumor genomes using long reads.

Most current studies rely on short-read sequencing to detect somatic structural variation (SV) in cancer genomes. Long-read sequencing offers the advantage of better mappability and long-range phasing, which results in substantial improvements in germline SV detection. However, current long-read SV detection methods do not generalize well to the analysis of somatic SVs in tumor genomes with complex rearrangements, heterogeneity, and aneuploidy. Here, we present Severus: a method for the accurate detection of different types of somatic SVs using a phased breakpoint graph approach. To benchmark various short- and long-read SV detection methods, we sequenced five tumor/normal cell line pairs with Illumina, Nanopore, and PacBio sequencing platforms; on this benchmark Severus showed the highest F1 scores (harmonic mean of the precision and recall) as compared to long-read and short-read methods. We then applied Severus to three clinical cases of pediatric cancer, demonstrating concordance with known genetic findings as well as revealing clinically relevant cryptic rearrangements missed by standard genomic panels.

Characterization of tumor evolution by functional clonality and phylogenetics in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a molecularly heterogeneous solid malignancy, and its fitness may be shaped by how its tumor cells evolve. However, ability to monitor tumor cell evolution is hampered by the presence of numerous passenger mutations that do not provide any biological consequences. Here we develop a strategy to determine the tumor clonality of three independent HCC cohorts of 524 patients with diverse etiologies and race/ethnicity by utilizing somatic mutations in cancer driver genes. We identify two main types of tumor evolution, i.e., linear, and non-linear models where non-linear type could be further divided into classes, which we call shallow branching and deep branching. We find that linear evolving HCC is less aggressive than other types. GTF2IRD2B mutations are enriched in HCC with linear evolution, while TP53 mutations are the most frequent genetic alterations in HCC with non-linear models. Furthermore, we observe significant B cell enrichment in linear trees compared to non-linear trees suggesting the need for further research to uncover potential variations in immune cell types within genomically determined phylogeny types. These results hint at the possibility that tumor cells and their microenvironment may collectively influence the tumor evolution process.

Small bowel perforation due to ingested frog bone: a case report.

Perforation of the gastrointestinal tract by ingested foreign body is an uncommon surgical emergency, most typically associated with the consumption of fish and chicken bones. We present an unusual case of a gentleman presenting emergently with an acute abdomen following ingestion of a meal containing frog meat. Emergent computed tomography (CT) revealed findings suggestive of jejunal perforation due to a foreign body. At laparotomy, a mid-jejunal site of perforation was noted due to a protruding piece of fractured frog bone. Washout and primary repair of the small bowel enterotomy were performed, and the patient made an excellent post-operative recovery.

Lymph node harvesting after laparoscopic complete mesocolic excision colectomy in colon cancer with practical application of glacial acid, absolute ethanol, water, and formaldehyde solution: A prospective cohort study.

Objectives: Quality of surgery has recently become an essential topic in the prognosis of colon cancer. Complete mesocolic excision for colon cancer has recently gained popularity with high-quality surgery. Patient specimens after complete mesocolic excision with central vessel ligation procedures have an integrity of the mesocolon and the yield of three fields of lymph node harvest. We apply the glacial acid, absolute ethanol, water, and formaldehyde solution to each specimen based on the Japanese classification of lymph node groups and station numbers. We aim to identify the distribution and status of lymph node metastasis according to each tumor site and some pathological characteristics related to this disease. Methods: A prospective cohort study was performed on 45 laparoscopic complete mesocolic excision surgery patients. Results: 2791 lymph nodes were harvested after complete mesocolic excision surgery. The average number was 62.0 ± 22.3 nodes. The mean tumor size (in the largest dimension) was 4.2 ± 1.8 cm. The average length of the resected bowel segments was 29.1 ± 7.7 cm. There are 63 (2.3%) node metastases in 2791 lymph nodes, in which 17/45 (37.8%) patients had pN(+). The minimum positive node size was 1 mm. The positive pericolic lymph nodes (station 1) accounted for the highest rate, with 53 nodes (1.9%). The number of lymph nodes in young age ⩽60 is more significant than in older. The results were similar, with a more significant node retrieval in the group with a tumor size >4.5 cm and specimen length >25 cm. The number of lymph nodes in lower tumor invasive (pT1,3) was smaller than pT4. Our research shows that the cecum, ascending, and descending colon had greater nodes than others, with a mean number of 78.6, 74.2, and 71.3, respectively. Conclusions: The metastasis and harvested lymph nodes accounted for the highest rate of colon cancer in station 1 and the lowest rate in station 3. The number of retrieved lymph nodes was significantly associated with tumor location, size, specimen length, and patient age.

Tailoring hierarchical structures in cellulose carbon aerogels from sugarcane bagasse using different crosslinking agents for enhancing electrochemical desalination capability.

Sugarcane bagasse is one of the most common Vietnamese agricultural waste, which possesses a large percentage of cellulose, making it an abundant and environmentally friendly source for the fabrication of cellulose carbon aerogel. Herein, waste sugarcane bagasse was used to synthesize cellulose aerogel using different crosslinking agents such as urea, polyvinyl alcohol (PVA) and sodium alginate (SA). The 3D porous network of cellulose aerogels was constructed by intermolecular hydrogen bonding, which was confirmed by Fourier transform infrared (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and nitrogen adsorption/desorption. Among the three cellulose aerogel samples, cellulose - SA aerogel (SB-CA-SA) has low density of 0.04 g m-3 and high porosity of 97.38%, leading to high surface area of 497.9 m2 g-1 with 55.67% micropores of activated carbon aerogel (SB-ACCA-SA). The salt adsorption capacity was high (17.87 mg g-1), which can be further enhanced to 31.40 mg g-1 with the addition of CNT. Moreover, the desalination process using the SB-ACCA-SA-CNT electrode was stable even after 50 cycles. The results show the great combination of cellulose from waste sugarcane bagasse with sodium alginate and carbon nanotubes in the fabrication of carbon materials as the CDI-utilized electrodes with high desalination capability and good durability.

Hybrid Nanoparticle for Co-delivering Paclitaxel and Dihydroartemisinin to Exhibit Synergic Anticancer Therapeutics.

AIM: Anticancer treatment is required to provide effective and safe patient medicines. This research aided in developing and applying nanoparticles (NPs) for cancer treatment. BACKGROUND: The poor solubility of paclitaxel (PTX) restricts its therapeutic efficacy because of allergic side effects caused by formulation excipients. To overcome this, PTX was coupled with artemisinin derivatives and loaded into an NP drug delivery system to enhance its effects while addressing its low solubility. OBJECTIVES: This study prepared and characterized a hybrid PLGA-lecithin NP containing dihydroartemisinin (DHA) and PTX for synergic anticancer therapy. A lyophilization study improved the stability of the NP drug formulations. METHODS: Dual PTX- and DHA-loaded PLGA- and lecithin-based NPs were prepared using a single-step solvent evaporation method. The NP suspensions were lyophilized, and the types and ratios of cryoprotectants were investigated. The physicochemical properties of NPs and lyophilized cakes (Lyo-NPs) were characterized. The stability of the Lyo-NPs was investigated at 2-8°C and room conditions. The anticancer effects of the drug combination, NP suspension, and lyophilized powder were analyzed using an in vitro cytotoxicity assay and an in vivo model. RESULTS: The optimal PTX-DHA loaded PLGA-lecithin-NP was formulated (200 nm, PDI: 0.248 ± 0.003, Zeta potential: -33.60 ± 3.39 mV). Mannitol was selected for lyophilization. Lyo-NPs improved the stability of the NPs (1 year), wherein the physicochemical properties of the NPs were maintained (RDI was close to 1.0). An in-vitro cytotoxicity assay of PTX combined with DHA showed a synergistic anticancer effect (CI <1.0). The suppressive effects of Lyo-NPs on tumor growth in vivo were dose-dependent. While the cocktail of free drugs showed high toxicity (7.5 mg PTX-15 mg DHA/kg) in-vivo, Lyo-NPs showed no statistical differences in hematological and biochemical parameters compared to the control. CONCLUSION: Dual-drug-loaded hybrid PLGA-lecithin NP is a potential system to minimize severe side effects while enhancing antitumor efficacy, in which lyophilization is a key process to increase stability.

An IROA Workflow for correction and normalization of ion suppression in mass spectrometry-based metabolomic profiling data.

Ion suppression is a major problem in mass spectrometry (MS)-based metabolomics; it can dramatically decrease measurement accuracy, precision, and signal-to-noise sensitivity. Here we report a new method, the IROA TruQuant Workflow, that uses a stable isotope-labeled internal standard (IROA-IS) plus novel companion algorithms to 1) measure and correct for ion suppression, and 2) perform Dual MSTUS normalization of MS metabolomic data. We have evaluated the method across ion chromatography (IC), hydrophilic interaction liquid chromatography (HILIC), and reverse phase liquid chromatography (RPLC)-MS systems in both positive and negative ionization modes, with clean and unclean ion sources, and across different biological matrices. Across the broad range of conditions tested, all detected metabolites exhibited ion suppression ranging from 1% to 90+% and coefficient of variations ranging from 1% to 20%, but the Workflow and companion algorithms were highly effective at nulling out that suppression and error. Overall, the Workflow corrects ion suppression across diverse analytical conditions and produces robust normalization of non-targeted metabolomic data.

Efficacy of Dyslipidemia Control by Combination Therapy with Rosuvastatin 10 Mg and Ezetimibe 10 Mg Compared with Rosuvastatin 20 Mg Monotherapy in Patients with Chronic Coronary Syndromes: A Randomized, Single-blind Controlled Trial.

BACKGROUND: Studies have shown the combination treatment effectiveness of using rosuvastatin and ezetimibe in patients with chronic coronary artery disease. Our study aim to evaluate the effectiveness of dyslipidemia treatment with the combination of rosuvastatin and ezetimibe 10mg in patients with chronic coronary artery disease compared with 20 mg rosuvastatin. OBJECTIVES: To evaluate the effectiveness of dyslipidemia treatment with the target of LDL-c < 1.4 mmol/L between combination therapy with rosuvastatin 10 mg and ezetimibe 10 mg in patients with chronic coronary artery disease compared with monotherapy increasing the dose of rosuvastatin 20 mg in Vietnam. METHODS: A randomized controlled clinical trial, single-blind, parallel-group with a 1:1 randomized ratio in 103 outpatients with chronic coronary syndromes treated with rosuvastatin 10mg daily. Group A received the combination therapy with rosuvastatin 10 mg plus ezetimibe 10 mg daily, and group B received rosuvastatin 20 mg daily. The primary outcome was to assess the efficacy of low-density lipoprotein - cholesterol (LDL-c) control between rosuvastatin 10 mg plus ezetimibe 10 mg versus rosuvastatin 20 mg after 4 weeks and 8 weeks. RESULTS: After 8 weeks of intervention, the proportion of archived treatment target patients with LDL-c < 1.4 mmol/L in groups A and B was 69.2% and 44.2%, respectively (Risk ratio (RR) = 1.57, p < 0.01), 50% LDL reduction was 27.9% and 55.8%, respectively (RR = 2.00, p < 0.01), and archived both targets were 51.9% and 25.6% (RR = 2.03, p < 0.01). CONCLUSION: Group A's LDL-c reduction effect and target achievement proportion (Rosuvastatin 10mg + Ezetimibe 10 mg) were significantly higher than Group B's (Rosuvastatin 20 mg). Both medication therapies were safe in patients, and the increased dose of monotherapy showed more side effects than the combination therapy.

Mismatch repair protein MLH1 suppresses replicative stress in BRCA2-deficient breast tumors.

Loss of BRCA2 (breast cancer 2) is lethal for normal cells. Yet it remains poorly understood how, in BRCA2 mutation carriers, cells undergoing loss of heterozygosity overcome the lethality and undergo tissue-specific neoplastic transformation. Here, we identified mismatch repair gene mutL homolog 1 (MLH1) as a genetic interactor of BRCA2 whose overexpression supports the viability of Brca2-null cells. Mechanistically, we showed that MLH1 interacts with Flap endonuclease 1 (FEN1) and competes to process the RNA flaps of Okazaki fragments. Together, they restrained the DNA2 nuclease activity on the reversed forks of lagging strands, leading to replication fork (RF) stability in BRCA2-deficient cells. In these cells, MLH1 also attenuated R-loops, allowing the progression of stable RFs, which suppressed genomic instability and supported cell viability. We demonstrated the significance of their genetic interaction by the lethality of Brca2-mutant mice and inhibition of Brca2-deficient tumor growth in mice by Mlh1 loss. Furthermore, we described estrogen as inducing MLH1 expression through estrogen receptor α (ERα), which might explain why the majority of BRCA2 mutation carriers develop ER-positive breast cancer. Taken together, our findings reveal a role of MLH1 in relieving replicative stress and show how it may contribute to the establishment of BRCA2-deficient breast tumors.