Solving olympiad geometry without human demonstrations.

Proving mathematical theorems at the olympiad level represents a notable milestone in human-level automated reasoning1-4, owing to their reputed difficulty among the world's best talents in pre-university mathematics. Current machine-learning approaches, however, are not applicable to most mathematical domains owing to the high cost of translating human proofs into machine-verifiable format. The problem is even worse for geometry because of its unique translation challenges1,5, resulting in severe scarcity of training data. We propose AlphaGeometry, a theorem prover for Euclidean plane geometry that sidesteps the need for human demonstrations by synthesizing millions of theorems and proofs across different levels of complexity. AlphaGeometry is a neuro-symbolic system that uses a neural language model, trained from scratch on our large-scale synthetic data, to guide a symbolic deduction engine through infinite branching points in challenging problems. On a test set of 30 latest olympiad-level problems, AlphaGeometry solves 25, outperforming the previous best method that only solves ten problems and approaching the performance of an average International Mathematical Olympiad (IMO) gold medallist. Notably, AlphaGeometry produces human-readable proofs, solves all geometry problems in the IMO 2000 and 2015 under human expert evaluation and discovers a generalized version of a translated IMO theorem in 2004.

A graph placement methodology for fast chip design.

Chip floorplanning is the engineering task of designing the physical layout of a computer chip. Despite five decades of research1, chip floorplanning has defied automation, requiring months of intense effort by physical design engineers to produce manufacturable layouts. Here we present a deep reinforcement learning approach to chip floorplanning. In under six hours, our method automatically generates chip floorplans that are superior or comparable to those produced by humans in all key metrics, including power consumption, performance and chip area. To achieve this, we pose chip floorplanning as a reinforcement learning problem, and develop an edge-based graph convolutional neural network architecture capable of learning rich and transferable representations of the chip. As a result, our method utilizes past experience to become better and faster at solving new instances of the problem, allowing chip design to be performed by artificial agents with more experience than any human designer. Our method was used to design the next generation of Google's artificial intelligence (AI) accelerators, and has the potential to save thousands of hours of human effort for each new generation. Finally, we believe that more powerful AI-designed hardware will fuel advances in AI, creating a symbiotic relationship between the two fields.

Fabrication of polydopamine-modified cellulose hydrogel for controlled release of α-mangostin.

Hydrogels are notable for their outstanding absorbent qualities, satisfactory compatibility with biological systems, ability to degrade, and inherent safety, all of which contribute to their high demand in the field of biomedicine. This study focuses on the fabrication of hydrogels using environmentally friendly cellulosic material. Cellulose hydrogel beads were prepared by physical cross-linking in a NaOH/urea medium. Furthermore, nano polydopamine was integrated into the hydrogel matrix as functional polymers and α-mangostin was employed as an active pharmaceutical ingredient. The physicochemical properties were comprehensively analyzed using Fourier-transform infrared spectrometer, 13C cross-polarization/magic angle spinning nuclear magnetic resonance, thermogravimetric analysis, and scanning electron microscope. The drug delivery properties, including water content, swelling ratio, and drug release profiles, were evaluated. In vitro cytotoxicity against MC3T3-E1 cells was assessed using sulforhodamine B staining. All test hydrogels exhibited inhibitory activity against the growth of MC3T3-E1 cells. These results indicated the potential use of these hydrogels as a drug delivery carrier for α-mangostin in the treatment of ankylosing spondylitis.

Hyponutrition among newly diagnosed gastric cancer.

OBJECTIVES: This study aims to determine the malnutrition status among Vietnamese patients newly diagnosed with gastric cancer (GC). BACKGROUND: GC remains the top rank of common and deadly diseases. With limited clinical manifestation, most GC patients were diagnosed at late stages when tumor is not radically resected. Malnutrition was associated with poor prognosis of GC, such as prolonged hospitalization, limited treatment efficacy and low survival rate. METHODS: The cross-sectional descriptive study recruited 77 patients newly diagnosed with GC and 90 healthy individuals (HC). The data used for this study were approved by the local Ethical Committee. The data were analysed on STATA 14.0 and GraphPad Prism 8.0. RESULTS: We observed the male dominant distribution in GC cohort and over 65% of GC were firstly diagnosed at advanced stages (III and IV). Anemia was detected in about 50% of GC patients. Hyponutrition was prevalent in newly diagnosed GC. We found the decreased tendency of anemia related indexes from HC to early stages (I and II) and advanced stages (III and IV) of GC patients. CONCLUSION: Anemia and hypoproteinemia occurred frequently among Vietnamese newly diagnosed GC. The nutrition therapy would benefit GC patients (Tab. 4, Fig. 4, Ref. 20).

Nanotherapeutics for immune network modulation in tumor microenvironments.

Immunotherapy has shown promise in cancer treatment, and is thus drawing increasing interest in this field. While the standard chemotherapy- and/or radiotherapy-based cancer treatments aim to directly kill cancer cells, immunotherapy uses host immune cell surveillance to fight cancer. In the tumor environment, there is a close relationship between tumor cells and the adjacent immune cells, which are largely suppressed by cancer-related regulation of immune checkpoints, immune-suppressive cytokines, and metabolic factors. The immune modulators currently approved for cancer treatment remain limited by issues with dose tolerance and insufficient efficacy. Researchers have developed and tested various nano-delivery systems with the goal of improving the treatment outcome of these drugs. By encapsulating immune modulators in particles and directing their tissue accumulation, some such systems have decreased immune-related toxicity while sharpening the antitumor response. Surface-ligand modification of nanoparticles has allowed drugs to be delivered to specific immune cells types. Researchers have also studied strategies for depleting or reprogramming the immune-suppressive cells to recover the immune environment. Combining a nanomaterial with an external stimulus has been used to induce immunogenic cell death; this favors the inflammatory environment found in tumor tissues to promote antitumor immunity. The present review covers the most recent strategies aimed at modulating the tumor immune environment, and discusses the challenges and future perspectives in developing nanoparticles for cancer immunotherapy.

Shared and unique antibody and B cell profiles in HIV-positive and HIV-negative individuals with cryptococcal meningoencephalitis.

Host non-T cell markers to aid in the diagnosis of cryptococcal meningoencephalitis (CM) have not been identified. In this case-control study, we characterized antibody and B cell profiles in HIV-negative and HIV-positive Vietnamese individuals of the Kinh ethnicity recently diagnosed with CM and controls. The study included 60 HIV-negative with no known immunocompromising condition and 60 HIV-positive individuals, with 30 CM cases and 30 controls in each group. Participants were matched by age, sex, HIV serostatus, and CD4 count in the HIV-positive group. Plasma immunoglobulin (Ig) levels, including IgG1, IgG2, IgM, and IgA, Cryptococcus spp. glucuronoxylomannan (GXM)- and laminarin (branched ${\rm{\beta }}$-[1-3]-glucan)-binding IgG, IgM, IgA levels, and peripheral blood B cell subsets were measured. Logistic regression, principal component, and mediation analyses were conducted to assess associations between antibody, B cell levels, and CM. The results showed that GXM-IgG levels were higher and IgG1 and IgG2 were lower in CM cases than controls, regardless of HIV status. In HIV-negative individuals, IgG2 mediated an inverse association between CD19+CD27+CD43+CD5- (B-1b-like) cells and CM. In HIV-positive individuals, lower levels of IgA, laminarin-IgA, and CD19+CD27+IgM+IgD- (IgM+ memory B) cells were each associated with CM. The shared and distinct antibody and B cell profiles identified in HIV-negative and HIV-positive CM cases may inform the identification of non-T-cell markers of CM risk or unsuspected disease, particularly in HIV-negative individuals.

Unlike cryptococcal meningitis (CM) in HIV-positive individuals, there are no known biomarkers of risk in HIV-negative individuals and the diagnosis is often not suspected and delayed. This study identified non-T cells, including antibody and B cell CM-associated profiles that may guide cryptococcal antigen testing in HIV-negative individuals.

Design, synthesis and evaluation the bioactivities of novel 1,3-dimethyl-6-amino-1H-indazole derivatives as anticancer agents.

Indoleamine 2,3-dioxygenase (IDO1) is a heme-containing enzyme mainly responsible for the metabolism of tryptophan to kynurenine. To date, the IDO1 inhibitors have been developed intensively for the re-activation of the anticancer immune response. In this report, we designed, and synthesized novel 1,3-dimethyl-6-amino indazole derivatives as IDO1 inhibitors based on the structure of IDO1 active site. We further examined their anticancer activity on hypopharyngeal carcinoma cells (FaDu), squamous cell carcinoma of the oral tongue (YD-15), breast cancer cells (MCF7), and human dental pulp stem cells (HDPSC). Of them, compound N-(4-bromobenzyl)-1,3-dimethyl-1H-indazol-6-amine (7) remarkably suppressed IDO1 expression in a concentration - dependent manner. In addition, 7 was the most potential anticancer compound with inducing apoptosis activity as well as selectively activated extracellular signal-regulated kinases (ERK) in mitogen-activated protein kinase (MAPK) pathways on FaDu cells. Finally, compound 7 suppressed cell mobility in wound healing assay with the reduced expression of matrix metalloproteinase MMP9. Taken together, we believe that 7 is the most promising compound, which may be applied to treatment of hypopharyngeal carcinoma.

Chemical Composition, Mosquito Larvicidal and Antimicrobial Activities, and Molecular Docking Study of Essential Oils of Cinnamomum melastomaceum, Neolitsea buisanensis and Uvaria microcarpa from Vietnam.

The leaf oil compositions of two Lauraceae and one Annonaceae plants cultivated in Vietnam were analysed by GC/MS (gas chromatography-mass spectrometry) analysis. The leaf oil of the first Lauraceae plant Cinnamomum melastomaceum contained 34 identified compounds, in which benzyl benzoate (38.5 %), linalool (19.9 %), (E)-caryophyllene (10.5 %), and α-terpineol (6.9 %) were the major compounds. The leaves of the second Lauraceae plant Neolitsea buisanensis gave an oil with the main compounds (E)-ß-ocimene (24.0 %), benzyl benzoate (15.8 %), bicyclogermacrene (14.9 %), and (E)-caryophyllene (6.3 %). The leaf oil of the Annonaceae plant Uvaria microcarpa consisted of the principal compounds (E)-caryophyllene (18.0 %), bicyclogermacrene (8.1 %), and δ-elemene (6.1 %). Two Lauraceae oil samples exhibited strong mosquito larvicidal activity against Aedes aegypti, Ae. albopictus, and Culex quinquefasciatus with LC50 and LD90 values of less than 50 µg/mL. The Annonaceae oil sample showed strong antimicrobial activity against the fungus Aspergillus niger ATCC 1015 with the MIC (minimum inhibitory concentration) value of 32 µg/mL. In the docking approach, the major compounds (E)-caryophyllene, bicyclogermacrene, and benzyl benzoate interacted with the mosquito odorant-binding protein 3OGN, whereas (E)-caryophyllene, bicyclogermacrene, and δ-elemene also potentially interacted with the 4ZA5 protein of fungus A. niger.

Increased Incidence of Ventilator-Acquired Pneumonia in Coronavirus Disease 2019 Patients: A Multicentric Cohort Study.

OBJECTIVES: Little is known about the epidemiology of ventilator-acquired pneumonia among coronavirus disease 2019 patients such as incidence or etiological agents. Some studies suggest a higher risk of ventilator-associated pneumonia in this specific population. DESIGN: Cohort exposed/nonexposed study among the REA-REZO surveillance network. SETTING: Multicentric; ICUs in France. PATIENTS: The coronavirus disease 2019 patients at admission were matched on the age, sex, center of inclusion, presence of antimicrobial therapy at admission, patient provenance, time from ICU admission to mechanical ventilation, and Simplified Acute Physiology Score II at admission to the patients included between 2016 and 2019 within the same surveillance network (1:1). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The overall incidence of ventilator-associated pneumonia, the cumulative incidence, and hazard rate of the first and the second ventilator-associated pneumonia were estimated. In addition, the ventilator-associated pneumonia microbiological ecology and specific resistant pattern in coronavirus disease 2019 exposed and nonexposed patients were compared. Medication data were not collected. A total of 1,879 patients were included in each group. The overall incidence of ventilator-associated pneumonia was higher among coronavirus disease 2019 exposed patients (25.5; 95% CI [23.7-27.45] vs 15.4; 95% CI [13.7-17.3] ventilator-associated pneumonia per 1,000 ventilation days). The cumulative incidence was higher for the first and the second ventilator-associated pneumonia among the coronavirus disease 2019 exposed patients (respective Gray test p < 0.0001 and 0.0167). The microbiological ecology and resistance were comparable between groups with a predominance of Enterobacterales and nonfermenting Gram-negative bacteria. The documented resistance pattern was similar between groups, except for a lower rate of methicillin-resistant Staphylococcus aureus in the coronavirus disease 2019 exposed patient (6% vs 23%; p = 0.013). CONCLUSIONS: There was a higher incidence of ventilator-associated pneumonia occurring among coronavirus disease 2019 patient compared with the general ICU population, with a similar microbiological ecology and resistance pattern.

Risk factors for disease severity and mortality of children with Covid-19: A study at a Vietnamese Children's hospital.

INTRODUCTION: To find out risk factors for disease severity and mortality of pediatric COVID-19 in the fourth wave of COVID-19 in Vietnam. METHODS: This retrospective cohort study was performed at Children's Hospital 1 from July to December 2021. All children with COVID-19 confirmed by a positive Realtime RT-PCR SARS-CoV-2 result and treated at COVID-19 department for at least 72 h were included. RESULTS: Of the 850 cases admitting to COVID-19 department, 555 children with COVID-19 confirmed by positive RT-PCR and treated at our center for more than 72 h. Median age of confirmed cases was 22.3 (IQR: 3.2-88.6) months, 55.1% were male, and 84.5% had a history of close contact with confirmed COVID-19 patients. The rate of mild, moderate and severe/critical cases was 73,7%, 9.0% and 17.3%, respectively. One hundred ninety-two children (34.6%) had underlying diseases, in which, neurologic disease was the most common underlying disease (7.9%). Underlying disease, dyspnea, elevated CRP >20 mg/L and elevated ferritin were independent factors related to severe illness. Twenty-point two percent of patients in our study needed respiratory support, including 22 invasive mechanical ventilation cases. Eighteen cases (3.2%) died because of severe comorbidities, poor response to treatment. CONCLUSIONS: In our study, the severe/critical and mortality rates in pediatric COVID-19 cases were relatively high. All fatal cases had severe comorbidities. Underlying disease, dyspnea, and elevated inflammatory markers were independent factors related to severity in pediatric COVID-19 cases.

Clinical and biological features of B-cell neoplasms with CDK6 translocations: an association with a subgroup of splenic marginal zone lymphomas displaying frequent CD5 expression, prolymphocytic cells, and TP53 abnormalities.

A translocation involving the cyclin-dependent kinase 6 (CDK6) gene [t(CDK6)] is a rare but recurrent abnormality in B-cell neoplasms. To further characterise this aberration, we studied 57 cases; the largest series reported to date. Fluorescence in situ hybridisation analysis confirmed the involvement of CDK6 in all cases, including t(2;7)(p11;q21) immunoglobulin kappa locus (IGK)/CDK6 (n = 51), t(7;14)(q21;q32) CDK6/immunoglobulin heavy locus (IGH) (n = 2) and the previously undescribed t(7;14)(q21;q11) CDK6/T-cell receptor alpha locus (TRA)/T-cell receptor delta locus (TRD) (n = 4). In total, 10 patients were diagnosed with chronic lymphocytic leukaemia, monoclonal B-cell lymphocytosis or small lymphocytic lymphoma, and 47 had small B-cell lymphoma (SmBL) including 36 cases of marginal zone lymphoma (MZL; 34 splenic MZLs, one nodal MZL and one bronchus-associated lymphoid tissue lymphoma). In all, 18 of the 26 cytologically reviewed cases of MZL (69%) had an atypical aspect with prolymphocytic cells. Among the 47 patients with MZL/SmBL, CD5 expression was found in 26 (55%) and the tumour protein p53 (TP53) deletion in 22 (47%). The TP53 gene was mutated in 10/30 (33%); the 7q deletion was detected in only one case, and no Notch receptor 2 (NOTCH2) mutations were found. Immunoglobulin heavy-chain variable-region (IGHV) locus sequencing revealed that none harboured an IGHV1-02*04 gene. Overall survival was 82% at 10 years and not influenced by TP53 aberration. Our present findings suggest that most t(CDK6)+ neoplasms correspond to a particular subgroup of indolent marginal zone B-cell lymphomas with distinctive features.

Prevalence, species distribution and antifungal susceptibility of Candida albicans causing vaginal discharge among symptomatic non-pregnant women of reproductive age at a tertiary care hospital, Vietnam.

BACKGROUND: Vaginal candidiasis is frequent in women of reproductive age. Accurate identification Candida provides helpful information for successful therapy and epidemiology study; however, there are very limited data from the Vietnam have been reported. This study was performed to determine the prevalence, species distribution of yeast causing vaginal discharge and antifungal susceptibility patterns of Candida albicans among symptomatic non-pregnant women of reproductive age. METHODS: Vaginal discharge samples were collected from 462 women of reproductive age in Hanoi, Vietnam between Sep 2019 and Oct 2020. Vaginal swabs from these patients were examined by direct microscopic examination (10% KOH). CHROMagar™ Candida medium and Sabouraud dextrose agar supplemented with chloramphenicol (0.5 g/l) were used to isolate yeast, and species identification was performed using morphological tests and molecular tools (PCR and sequencing). Antifungal susceptibility testing was determined according to the Clinical and Laboratory Standards Institute guidelines (M27-A3 and M27-S4). RESULTS: The prevalence of vaginal yeast colonization in non-pregnant women was 51.3% of 462 participants. Nine different yeast species were identified. Among these isolates, C. albicans (51.37%) was the most frequent, followed by C. parapsilosis (25.88%), C. glabrata (11.37%), C. tropicalis (4.31%), C. krusei (3.92%), C. africana (1.57%), Saccharomyces cerevisiae (0.78%), C. nivariensis (1 isolates, 0.39%), and C. lusitaniae (1 isolates, 0.39%), respectively. Among C. albicans, all 46 isolates were 100% susceptible to micafungin, caspofungin, and miconazole. The susceptibility rates to amphotericine B, 5-flucytosine, fluconazole, itraconazole and voriconazole were 95.65, 91.30, 91.30, 82.61 and 86.95%, respectively. CONCLUSIONS: The prevalence of VVC among symptomatic non-pregnant women of reproductive age in Vietnam was higher than many parts of the world. The high frequency of non-albicans Candida species, which were often more resistant to antifungal agents, was a notable feature. Resistance rates of vaginal C. albicans isolates to antifungal agents was low. Our findings suggest that continued surveillance of changes in species distribution and susceptibility to antifungals should be routinely screened and treated.

Effect of Probiotic Supplementation on Glycemic Outcomes in Patients with Abnormal Glucose Metabolism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: The effectiveness of probiotics in patients with abnormal glucose metabolism has not been clearly demonstrated. It is also unclear if outcomes are consistent across different probiotic formulations. METHODS: A literature search was conducted using PubMed, EMBASE, and Cochrane CENTRAL database from inception through May 2020. Randomized controlled trials that evaluated the effect of probiotics on fasting blood glucose (FBG) or hemoglobin A1c (HbA1c) in patients with prediabetes, type 2 diabetes mellitus, or gestational diabetes were included. Outcomes of interest included FBG, HbA1c, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of ß-cell function (HOMA-B), and quantitative insulin sensitivity check index (QUICKI). Weighted mean difference (WMD) and 95% confidence intervals (CIs) were calculated using the DerSimonian and Laird random-effects model. RESULTS: 31 studies involving 1,948 participants were included in this analysis. Compared to control, probiotics had a significant favorable effect on FBG (WMD -5.77 mg/dL, 95% CI -8.48 to -3.06), HbA1c (WMD -0.32%, 95% CI -0.47 to -0.18), fasting insulin (WMD -2.95 µIU/mL, 95% CI -3.76 to -2.14), HOMA-IR (WMD -0.82, 95% CI -1.05 to -0.59), HOMA-B (WMD -14.86, 95% CI -24.57 to -5.16), and QUICKI (WMD 0.015, 95% CI 0.011-0.019). Further, probiotics were associated with favorable outcomes on all parameters at doses between 1 and 10 × 109 colony-forming unit per day (p < 0.004 for all) and formulations containing 2-4 strains (p < 0.05 for all). DISCUSSION/CONCLUSION: Probiotics appear to have a modest effect on glycemic parameters in patients with abnormal glucose metabolism. Due to the limited number of trials conducted in patients with prediabetes, more studies are warranted in this population.

Seven traditional Chinese herbal extracts fermented by Lactobacillus rhamnosus provide anti-pigmentation effects by regulating the CREB/MITF/tyrosinase pathway.

Skin pigmentation is resulted from several processes, such as melanin synthesis transportation and abnormal melanin accumulation in keratinocytes. Various studies have suggested that seven traditional Chinese herbal extracts from Atractylodes macrocephala, Paeonia lactiflora, Bletilla striata, Poria cocos, Dictamnus dasycarpus, Ampelopsis japonica and Tribulus terrestris (which we collectively named ChiBai), show several protective effects toward skin-related diseases. Lactobacillus rhamnosus, a lactic acid bacterium, has been reported to treat skin inflammation and atopic dermatitis. In this study, the broth produced by the cofermentation of ChiBai with Lactobacillus rhamnosus was studied for its effects on skin pigmentation through in vitro and in vitro experiments. In the in vitro experiments, we found that the fermented broth of ChiBai (FB-ChiBai) suppressed alpha-melanocyte stimulating hormone (α-MSH)-induced melanogenesis in B16F0 murine melanoma cells without any cytotoxicity at a concentration of 0.5%. FB-ChiBai significantly attenuated melanin production, tyrosinase activities and melanogenesis-related signaling pathways. Treatment with FB-ChiBai also reduced the nuclear translocation and promoter binding activities of MITF. In the in vivo experiments, FB-ChiBai was topically applied to the dorsal skin of C57BL/6J nude mice and concurrently irradiated with UVB, three times a week for 8 weeks. The results indicated that FB-ChiBai alleviated UVB-induced hyperpigmentation by reducing epidermal hyperplasia and inhibiting the CREB/MITF/tyrosinase pathway. In conclusion, our data indicated that the anti-melanogenic effects of FB-ChiBai are mediated by the inhibition of CREB/MITF/tyrosinase signaling pathway. The findings suggest that FB-ChiBai can protect against UV-B irradiation and that it might be used as an agent in cosmetic products to protect against UVB-induced hyperpigmentation.

O/SEA/Mya-98 lineage foot-and-mouth disease virus was responsible for an extensive epidemic that occurred in late 2018 in Vietnam.

Since late 2018, foot-and-mouth disease (FMD) has reemerged and rapidly swept through pig farms in North and Central Vietnam, despite widespread use of commercial FMD vaccines. To investigate the FMD virus (FMDV) strains responsible for the current epidemics, 40 FMDV samples were collected from 17 provinces during November-December 2018, and the VP1 coding genes were sequenced and analyzed. Phylogenetic analysis and sequence comparisons revealed that all of the reemerging Vietnamese FMDVs belonged to the Mya-98 lineage of the O/Southeast Asia topotype (O/SEA/Mya-98) and shared high nucleotide (99.06-100% identity) and amino acid (97.65-100% identity) sequence similarity with each other. The study results suggested that the reemerging FMDVs originated from local Vietnamese strains. Field viruses had different amino acids in the antigenic sites of VP1 when compared to the strains used in the vaccines. The present study provides an important basis for vaccine selection in the battle against FMD in Vietnam.

Reproductive Outcomes following Laser Surgery for Twin-Twin Transfusion Syndrome.

BACKGROUND: There are limited studies describing future reproductive outcomes in women who have had selective fetoscopic laser photocoagulation (SFLP) for twin-twin transfusion syndrome (TTTS). OBJECTIVE: Our study aims to compare reproductive outcomes following monochorionic multiple gestational pregnancies complicated by TTTS requiring SFLP to those not requiring SFLP. METHODS: This is a retrospective cohort study that analyzed records of patients who were evaluated at the Cincinnati Fetal Center (2007-2014) for monochorionic multiple gestations. A questionnaire regarding reproductive, obstetric, gynecologic, and psychological outcomes following the index pregnancy was administered to consented participants by electronic distribution. The data was compared between pregnancies with prior SFLP versus no prior SFLP. RESULTS: There was a higher response rate in the SFLP group (219/474, 46.2%) versus the referent group (62/187, 33.2%). The median interval between the index pregnancy and survey completion was 74 months and 46 months in the SFLP and referent groups, respectively. Approximately 38 and 37% of the women in the SFLP and referent groups attempted conception after the index pregnancy with a >90% pregnancy success rate in both groups. Use of assisted reproductive technology was highly prevalent in both the index and subsequent pregnancies, with no significant difference between the groups. Over 60% of the women in each group did not attempt future pregnancy. Of those, approximately 1 in 3 cited the outcome of the index pregnancy as the primary reason for not pursuing future conception. There were no significant differences in selected maternal-fetal complications and new-onset gynecologic problems. More than 1 in 4 women in both groups were diagnosed with a mental health disorder following the index pregnancy. CONCLUSION: SFLP does not appear to be associated with adverse reproductive, obstetric, or gynecologic outcomes. The data may help facilitate evidence-based counseling for this patient population.

Antiproliferative activity and apoptosis induction by trijuganone C isolated from the root of Salvia miltiorrhiza Bunge (Danshen).

In this study, we found that the hexane fraction of Danshen, the dried root of Salvia miltiorrhiza (Lamiaceae), exerted antiproliferative effects on human leukemia cells. Phytochemical investigation of the hexane fraction achieved the isolation of the tanshinone diterpenes: dihydrotanshinone I (1), trijuganone C (2), trijuganone B (3), cryptotanshinone (4), tanshinone IIA (5), and tanshinone I (6). Compound 2 showed significant antiproliferative activities against human leukemia cells HL-60, Jurkat, and U937. The antiproliferative activities of 2 against human cancer and normal cells indicated that 2 exhibited potent antiproliferative activities with IC50 values less than 10 µM against HL-60 and Jurkat cells as well as on the colon cancer cells DLD-1, COLO 205, and Caco-2. Compound 2 induced chromatin condensation, DNA fragmentation, activation of caspase-3, -8, and -9, and the cleavage of poly (ADP-ribose) polymerase (PARP) in HL-60 cells. Moreover, 2 activated Bid and Bax, leading to the loss of mitochondrial membrane potential, and 2 induced the cytochrome c release from mitochondria into cytosol. In contrast, Bcl-2 and Bcl-xL were unaffected by 2. These results suggest that 2 exerts antiproliferative effects via apoptosis induction mediated by mitochondrial dysfunction and caspase activation. Compound 2 may serve as a candidate of potential chemotherapeutic agent for human leukemia.