Prospective Exploratory Study of the Effects of Postoperative Endocrine Medication on the Endometrium in Breast Cancer Patients.

Objective: This study aimed to investigate the pathological effects of long-term postoperative endocrine medication on the endometrium in breast cancer patients. Methods: Data of 99 patients with primary breast cancer who underwent hysteroscopy and obtained endometrial biopsy from 1 June 2018 to 31 December 2021 at the Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital were prospectively collected. Results: Hysteroscopy was performed followed by endometrial histopathological examination in 99 breast cancer patients, including 44 taking tamoxifen (TAM), 26 taking other endocrine drugs, and 29 not taking endocrine drugs. The endometrial thickness in the TAM group was significantly higher than that in the other endocrine drug groups and the group not taking endocrine drugs (p=0.017). The receiver operating characteristic curves for the abnormal premenopausal endometrial thickening were plotted in this study; an endometrial thickness of 15.5 mm seen on ultrasound could be used as the most accurate ultrasound diagnostic threshold for the diagnosis of abnormal premenopausal endometrial hyperplasia, with an area under the curve of 0.888 (95% CI: 0.716, 1.000), a sensitivity of 100%, and a specificity of 75%, which was consistent with the results of our previous retrospective study. An endometrial thickness of ≥5 mm in postmenopausal women with breast cancer taking TAM was still used as the cut-off value for routine ultrasound diagnosis of abnormal postmenopausal endometrial hyperplasia. Conclusion: An ultrasound endometrial thickness (proliferative phase) of >15 mm in premenopausal patients can be used as the most accurate ultrasound diagnostic threshold for the diagnosis of abnormal endometrial hyperplasia. After menopause, an ultrasound endometrial thickness of ≥5 mm is still used as the criterion for diagnosing abnormal endometrial hyperplasia. Older patients should be monitored for signs of vaginal bleeding and fluid discharge, and hysteroscopy should be performed if necessary to ascertain the endometrial condition.

High-Quality Genome Assembly and Genome-Wide Association Study of Male Sterility Provide Resources for Flax Improvement.

Flax is an economic crop with a long history. It is grown worldwide and is mainly used for edible oil, industry, and textiles. Here, we reported a high-quality genome assembly for "Neiya No. 9", a popular variety widely grown in China. Combining PacBio long reads, Hi-C sequencing, and a genetic map reported previously, a genome assembly of 473.55 Mb was constructed, which covers ~94.7% of the flax genome. These sequences were anchored onto 15 chromosomes. The N50 lengths of the contig and scaffold were 0.91 Mb and 31.72 Mb, respectively. A total of 32,786 protein-coding genes were annotated, and 95.9% of complete BUSCOs were found. Through morphological and cytological observation, the male sterility of flax was considered dominant nuclear sterility. Through GWAS analysis, the gene LUSG00017705 (cysteine synthase gene) was found to be closest to the most significant SNP, and the expression level of this gene was significantly lower in male sterile plants than in fertile plants. Among the significant SNPs identified in the GWAS analysis, only two were located in the coding region, and these two SNPs caused changes in the protein encoded by LUSG00017565 (cysteine protease gene). It was speculated that these two genes may be related to male sterility in flax. This is the first time the molecular mechanism of male sterility in flax has been reported. The high-quality genome assembly and the male sterility genes revealed, provided a solid foundation for flax breeding.

The Regiocontrollable Enantioselective Synthesis of Chiral Trifluoromethyl-Containing Spiro-Pyrrolidine-Pyrazolone Compounds via Amino-Regulated 1,3-Proton Migration Reaction.

An amino-controlled regiodivergent asymmetric synthesis of CF3-containing spiro-pyrrolidine-pyrazolone compounds is described. With alkaloid-derived squaramide as catalyst, the 1,3-dipolar cycloaddition of α,ß-unsaturated pyrazolone with diethyl 2-((2,2,2-trifluoroethyl)imino) malonate offered adducts in excellent yields, dr, and ee. While the cyclohexanediamine-derived squaramide was employed, the reaction afforded a series of structure isomers through a switched umpolung reaction.

Predicting fetal weight by three-dimensional limb volume ultrasound (AVol/TVol) and abdominal circumference.

BACKGROUND: Fetal weight is an important parameter to ensure maternal and child safety. The purpose of this study was to use three-dimensional (3D) limb volume ultrasound combined with fetal abdominal circumference (AC) measurement to establish a model to predict fetal weight and evaluate its efficiency. METHODS: A total of 211 participants with single pregnancy (28-42 weeks) were selected between September 2017 and December 2018 in the Beijing Obstetrics and Gynecology Hospital of Capital Medical University. The upper arm (AVol)/thigh volume (TVol) of fetuses was measured by the 3D limb volume technique. Fetal AC was measured by two-dimensional ultrasound. Nine cases were excluded due to incomplete information or the interval between examination and delivery >7 days. The enrolled 202 participants were divided into a model group (134 cases, 70%) and a verification group (68 cases, 30%) by mechanical sampling method. The linear relationship between limb volume and fetal weight was evaluated using Pearson Chi-squared test. The prediction model formula was established by multivariate regression with data from the model group. Accuracy of the model formula was evaluated with verification group data and compared with traditional formulas (Hadlock, Lee2009, and INTERGROWTH-21st) by paired t-test and residual analysis. Receiver operating characteristic curves were generated to predict macrosomia. RESULTS: AC, AVol, and TVol were linearly related to fetal weight. Pearson correlation coefficient was 0.866, 0.862, and 0.910, respectively. The prediction model based on AVol/TVol and AC was established as follows: Y = -481.965 + 12.194TVol + 15.358AVol + 67.998AC, R2adj = 0.868. The scatter plot showed that when birth weight fluctuated by 5% (i.e., 95% to 105%), the difference between the predicted fetal weight by the model and the actual weight was small. A paired t-test showed that there was no significant difference between the predicted fetal weight and the actual birth weight (t = -1.015, P = 0.314). Moreover, the residual analysis showed that the model formula's prediction efficiency was better than the traditional formulas with a mean residual of 35,360.170. The combined model of AVol/TVol and AC was superior to the Lee2009 and INTERGROWTH-21st formulas in the diagnosis of macrosomia. Its predictive sensitivity and specificity were 87.5% and 91.7%, respectively. CONCLUSION: Fetal weight prediction model established by semi-automatic 3D limb volume combined with AC is of high accuracy, sensitivity, and specificity. The prediction model formula shows higher predictive efficiency, especially for the diagnosis of macrosomia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03002246; https://clinicaltrials.gov/ct2/show/NCT03002246?recrs=e&cond=fetal&draw=8&rank=67.

Catalytic Asymmetric Construction of Tertiary Carbon Centers Featuring an α-Difluoromethyl Group with CF2H-CH2-NH2 as the "Building Block".

We report here for the first time a novel difluoromethylated ketimine building block condensed by thioisatin and difluoroethylamine, offering efficient access to a broad range of enantioenriched products bearing difluoroethylamine units (27 examples, ≤98% yield, >99% ee) in the presence of quinine-derived squaramide. Further transformation of the intermediate would generate a variety of versatile functional blocks like α-difluoromethyl amines, ß-amino acid, and ß-diamine with retention of the enantiomeric excess at the difluoromethyl-bound carbon.

Down-regulation of miR-556-3p inhibits hemangioma cell proliferation and promotes apoptosis by targeting VEGFC.

The purpose of this study was to determine the effect of microRNA (miR)-556-3p on cell proliferation and apoptosis of hemangioma-derived endothelial cells (HemECs).  qRT-PCR was used to compare the expressions of miR-556-3p in HemECs and normal cells. The target gene was identified using dual-luciferase reporter assay. Cell proliferation was measured with MTT assay, while western blotting was used to assay VEGFC expression levels. Apoptosis was assayed with FITC Annexin V Apoptosis assay kit. miR-556-3p was overexpressed in HemECs. Transfection with miR-556-3p inhibitor resulted in decreased proliferation of HemECs (p<0.05). The expression of the target gene of miR-556-3pi.e. VEGFC was upregulated when miR-556-3p inhibitor was transfected. The transfection also resulted in increased apoptosis. In HemECs, miR-556-3p is overexpressed and VEGFC expression is low. Thus, miR-556-3p or VEGFC might be potential targets for treatment of angiosarcoma.

Causes of misdiagnosis in assessing tubal patency by transvaginal real-time three-dimensional hysterosalpingo-contrast sonography.

OBJECTIVE: This study aims to investigate the causes of misdiagnosis in assessing tubal patency by transvaginal real-time three-dimensional hysterosalpingo-contrast sonography (TVS RT-3D-HyCoSy), in order to improve the diagnostic efficiency of TVS RT-3D-HyCoSy. METHODS: A total of 162 oviducts of 83 infertility patients were examined by TVS RT-3D-HyCoSy. These results were compared with the gold standard for laparoscopic dye studies, and the misdiagnosed cases were analyzed. RESULTS: TVS RT-3D-HyCoSy revealed that 68 oviducts were unobstructed and 94 obstructed. The results for the 144 oviducts were in line with the gold standard, while those for 18 oviducts were not. The accuracy rate of the TVS RT-3D-HyCoSy was 88.9%, and the misdiagnosis rate was 11.1%. The main causes of misdiagnosis included contrast medium countercurrent and diffusion, oviduct spasm, abnormal shape or position of the oviduct, pelvic adhesion, and poor imaging operation. CONCLUSION: TVS RT-3D-HyCoSy can well-evaluate tubal patency, and understand and improve the cause of misdiagnosis. Furthermore, the diagnostic efficiency of TVS RT-3D-HyCoSy can still be further improved.

Causes of misdiagnosis in assessing tubal patency by transvaginal real-time three-dimensional hysterosalpingo-contrast sonography

SUMMARY OBJECTIVE This study aims to investigate the causes of misdiagnosis in assessing tubal patency by transvaginal real-time three-dimensional hysterosalpingo-contrast sonography (TVS RT-3D-HyCoSy), in order to improve the diagnostic efficiency of TVS RT-3D-HyCoSy. METHODS A total of 162 oviducts of 83 infertility patients were examined by TVS RT-3D-HyCoSy. These results were compared with the gold standard for laparoscopic dye studies, and the misdiagnosed cases were analyzed. RESULTS TVS RT-3D-HyCoSy revealed that 68 oviducts were unobstructed and 94 obstructed. The results for the 144 oviducts were in line with the gold standard, while those for 18 oviducts were not. The accuracy rate of the TVS RT-3D-HyCoSy was 88.9%, and the misdiagnosis rate was 11.1%. The main causes of misdiagnosis included contrast medium countercurrent and diffusion, oviduct spasm, abnormal shape or position of the oviduct, pelvic adhesion, and poor imaging operation. CONCLUSION TVS RT-3D-HyCoSy can well-evaluate tubal patency, and understand and improve the cause of misdiagnosis. Furthermore, the diagnostic efficiency of TVS RT-3D-HyCoSy can still be further improved.

RESUMO OBJETIVO Este estudo tem como objetivo investigar as causas do diagnóstico equivocado na avaliação da patência tubária por meio da ultrassonografia de contraste histerosalpingo em tempo real transvaginal (TVS RT-3D-HyCoSy), a fim de melhorar a eficiência diagnóstica das TVS RT-3D-HyCoSy. MÉTODOS Um total de 162 ovidutos em 83 pacientes da infertilidade foi examinado por TVS RT-3D-HyCoSy. Esses resultados foram comparados com o padrão ouro para estudos de tintura laparoscópica, e os casos diagnosticados erroneamente foram analisados. RESULTADOS TVS RT-3D-HyCoSy revelaram que 68 ovidutos foram desobstruídos e 94 ovidutos foram obstruídos. Os resultados para os 144 ovidutos estavam em consonância com o padrão ouro, enquanto que aqueles para os 18 ovidutos, não. A taxa de acurácia do TVS RT-3D-HyCoSy foi de 88,9%, e a taxa de erro de diagnóstico foi de 11,1%. As principais causas de erro de diagnóstico incluíram contraponto e difusão do meio de contraste, espasmo do oviduto, forma ou posição anormal do oviduto, adesão pélvica e má operação de imagem. CONCLUSÃO TVS RT-3D-HyCoSy pode bem avaliar a patência tubária, e compreender e melhorar a causa do erro de diagnóstico. Além disso, a eficiência diagnóstica do TVS RT-3D-HyCoSy ainda pode ser melhorada.

The catalytic asymmetric synthesis of CF3-containing spiro-oxindole-pyrrolidine-pyrazolone compounds through squaramide-catalyzed 1,3-dipolar cycloaddition.

Pharmaceutically important compounds were synthesized through the organocatalytic 1,3-dipolar cycloaddition reaction. In the presence of a cinchonine-derived squaramide catalyst, the cycloaddition of N-2,2,2-trifluoroethylisatin ketimines with α,ß-unsaturated pyrazolones gave a spiro-pyrrolidine-linked oxindole and pyrazolone compound bearing four consecutive stereocenters and two vicinal spiroquaternary chiral centers, in excellent yields and stereoselectivities.

The asymmetric construction of CF3-containing spiro-thiazolone-pyrrolidine compounds via [3 + 2] cycloaddition.

The first organocatalytic method for the asymmetric construction of CF3-containing spiro-thiazolone-pyrrolidine compounds has been developed. This is one of the very few methods to reach spiro-thiazolones, and afforded the products in excellent yields and stereoselectivities catalysed by only 1 mol% cinchona alkaloid-derived catalyst.

Synthesis of Chloro(phenyl)trifluoromethyliodane and Catalyst-Free Electrophilic Trifluoromethylations.

The present work deals with a challenge in the synthesis of aryltrifluoromethyliodanes (ArICF3X) and develops a direct route to PhICF3Cl via a simple ligand-exchange reaction of PhI(OCOCF3)2, Me3SiCF3, and NaCl for the first time. The I-Cl bond length in PhICF3Cl supports its iodonium character, which enables an enhanced CF3-transfer capability in electrophilic S-, O-, N-, and C-trifluoromethylations as well as in catalyst-free trifluoromethylation-cyclizations of arylisonitriles.

Construction of an SNP-based high-density linkage map for flax (Linum usitatissimum L.) using specific length amplified fragment sequencing (SLAF-seq) technology.

Flax is an important crop for oil and fiber, however, no high-density genetic maps have been reported for this species. Specific length amplified fragment sequencing (SLAF-seq) is a high-resolution strategy for large scale de novo discovery and genotyping of single nucleotide polymorphisms. In this study, SLAF-seq was employed to develop SNP markers in an F2 population to construct a high-density genetic map for flax. In total, 196.29 million paired-end reads were obtained. The average sequencing depth was 25.08 in male parent, 32.17 in the female parent, and 9.64 in each F2 progeny. In total, 389,288 polymorphic SLAFs were detected, from which 260,380 polymorphic SNPs were developed. After filtering, 4,638 SNPs were found suitable for genetic map construction. The final genetic map included 4,145 SNP markers on 15 linkage groups and was 2,632.94 cM in length, with an average distance of 0.64 cM between adjacent markers. To our knowledge, this map is the densest SNP-based genetic map for flax. The SNP markers and genetic map reported in here will serve as a foundation for the fine mapping of quantitative trait loci (QTLs), map-based gene cloning and marker assisted selection (MAS) for flax.

Me3SiCF2Br-Self-Assisted Domino Reaction: Catalytic Synthesis of α,α-Difluorocyclopentanones from Methylvinylketones.

A complete self-assistance strategy based on Me3SiCF2Br was used in the domino conversion of methylvinylketones into α,α-difluorinated cyclopentanones. Initiated by 5 mol % of nBu4NBr, the multistep reaction occurred in one pot under mild conditions via the in situ formation of silyl dienol ethers, difluorocyclopropanation, thermal vinylcyclopropane-cyclopentene rearrangement, and desilylation. The process takes advantage of the multitasking capability of Me3SiCF2Br as the difluorocarbene source, a silicon-based transfer agent, and a bromine anion releaser.