Tumor Stroma Content Regulates Penetration and Efficacy of Tumor-targeting Bacteria.

Bacteria-based cancer therapy (BBCT) strains grow selectively in primary tumors and metastases, colonize solid tumors independent of genetics, and kill cells resistant to standard molecular therapy. Clinical trials of BBCT in solid tumors have not reported any survival advantage yet, partly due to the limited bacterial colonization. Collagen, abundant in primary and metastatic solid tumors, has a well-known role in hindering intratumoral penetration of therapeutics. Nevertheless, the effect of collagen content on the intratumoral penetration and antitumor efficacy of BBCT is rarely unexplored. We hypothesized that the presence of collagen limits the penetration and, thereby, the antitumor effects of tumor-selective Salmonella. Typhimurium VNP20009 cheY+. We tested our hypothesis in low and high collagen content tumor spheroid models of triple-negative murine breast cancer. We found that high collagen content significantly hinders bacteria transport in tumors, reducing bacteria penetration and distribution by ~7-fold. The higher penetration of bacteria in low collagen-content tumors led to an overwhelming antitumor effect (~73% increase in cell death), whereas only a 28% increase in cell death was seen in the high collagen-content tumors. Our mathematical modeling of intratumoral bacterial colonization delineates the role of growth and diffusivity, suggesting an order of magnitude lower diffusivity in the high collagen-content tumors dominates the observed outcomes. Finally, our single-cell resolution analysis reveals a strong spatial correlation between bacterial spatial localization and collagen content, further corroborating that collagen acts as a barrier to bacterial penetration despite S. Typhimurium VNP20009 cheY+ motility. Understanding the effect of collagen on BBCT performance could lead to engineering more efficacious BBCT strains capable of overcoming this barrier to colonization of primary tumors and metastases.

[Effect of CKIP-1 on hepatocyte apoptosis in nonalcoholic fatty liver disease].

Objective: To explore the effect and underlying mechanism of casein kinase 2 interacting protein-1 (CKIP-1) on hepatocyte apoptosis in nonalcoholic fatty liver disease (NAFLD). Methods: Experimental study. An NAFLD cell model was established by inducing human hepatoma cell line, HepG2 cells, with oleic acid (OA). Flag-CKIP-1 expression vector and shRNA-CKIP-1 were transfected into HepG2 cells. Flow cytometry was used to detect the effect of CKIP-1 on the activity and apoptosis of NAFLD hepatocytes. The levels of apoptosis-related proteins were detected by Western blot. CKIP-1 knockout mice in C57BL/6 back-ground were fed with either standard or high-fat diet for 8 weeks. Apoptosis-related signal proteins in NAFLD hepatocytes were detected by immunohistochemistry. Results: After CKIP-1 was transfected into HepG2 cells, the degree of OA induced cell liposis was significantly reduced (P<0.05). Annexin V-FITC/PI flow cytometry showed that CKIP-1 reduced the apoptosis of steatotic hepatocytes. Overexpression of CKIP-1 could significantly inhibit the expression of caspase-3 and caspase-9 and increase the expression of Bcl-2/Bax (P<0.05). Knockdown of CKIP-1 could increase the expression of caspase-3 and caspase-9 (P<0.05). CKIP-1 knockout could further increase the expression of caspase-3 and caspase-9 in NAFLD mice (P<0.01,P<0.05), and further decrease the expression of Bcl-2/Bax (P<0.05). Conclusion: CKIP-1 inhibited the apoptosis of steatotic hepatocytes by up-regulating the expression of apoptosis inhibitor gene, Bcl-2/Bax, and affecting the proteases, caspase-3 and caspase-9.

CXCL12/CXCR4 Mediates Orthodontic Root Resorption via Regulating the M1/M2 Ratio.

Mechanical force-induced external root resorption is a major clinical side effect of orthodontic treatment. Recent work has revealed that M1 macrophages play a vital role in promoting orthodontic root resorption (ORR), but the mechanism of how mechanical force stimulation increases the M1/M2 macrophage ratio in periodontal tissue is poorly understood. In the current study, we showed that C-X-C motif chemokine 12 (CXCL12)+ periodontal ligament cells (PDLCs) and C-X-C chemokine receptor type 4 (CXCR4)+ monocytes in the periodontal ligament (PDL) were significantly increased after force application with ongoing root resorption, and these effects were partially rescued after force removal in mice. The expression of CXCL12 in PDLCs was increased by force stimulation in a time- and intensity-dependent manner in vitro. Blockage of the CXCL12/CXCR4 axis using CXCR4 antagonist AMD3100 was sufficient to alleviate ORR and reverse the force-enhanced M1/M2 macrophage ratio. Further mechanism exploration showed that Ly6Chi inflammatory monocytes homed in a CXCL12/CXCR4 axis-dependent manner. The number and proportion of CD11b+ Ly6Chi inflammatory monocytes in cervical lymph nodes were significantly increased by force loading, accompanied by decreased CD11b+ Ly6Chi monocytes in the blood. These changes were blunted by intraperitoneal injection of AMD3100. In addition, blockage of the CXCL12/CXCR4 axis effectively reversed M2 suppression and promoted M1 polarization. Collectively, results indicate that force-induced CXCL12/CXCR4 axis mediates ORR by increasing the M1/M2 ratio in periodontal tissues through attracting Ly6Chi inflammatory monocytes and modulating macrophage polarization. The results also imply that AMD3100 is potentially inhibitory to root resorption.

[Determinants of disability free life expectancy in Chinese elderly: based on Multi-states Markov model].

objective: To understand and quantify the main influencing factors related to disability free life expectancy (DFLE) among Chinese elderly. Methods: Using publicly available data from the Chinese Longitudinal Healthy Longevity Survey (2011-2018), we fitted multi-states Markov model and microsimulation to estimate DFLE at age 65, life expectancy (LE) at age 65 and proportion of DFLE to LE (DFLE/LE) at age 65. We calculated 95%CI by Bootstrap. Result: DFLE of the Chinese elderly aged 65 was 14.27 (95%CI: 13.85-14.74) years, higher in female than male and higher in elderly with higher economic status. DFLE/LE at age 65 was 86.33% (95%CI: 85.52%-87.18%), higher in male than female and rural than urban. The risk factors of DFLE include not undergoing physical examination, inadequate fruit/vegetable intake, smoking, and feeling stress, leading to 0.74, 0.41, 0.62, 0.12 years of DFLE lost for male, and 0.82, 0.42, 0.19, 0.20 years of DFLE lost for female, respectively. Eliminating these risk factors can improve DFLE at age 65 by 1.73 years for male and 1.45 years for female. Conclusions: Policies targeting male elderly and the elderly with lower economic status, and measures promoting physical examination and adequate fruit/vegetable intake, relieving stress and banning smoking can substantially improve DFLE of Chinese elderly.

[Application of AGREEâ ¡ in evaluating quality of esophageal cancer screening practice guidelines].

High-quality clinical practice guidelines are of great significance for standardizing the clinical diagnosis and treatment process and improving the overall quality of health care. The Appraisal of Guidelines for Research & Evaluation InstrumentⅡ (AGREEⅡ) is one of the recognized tools for the evaluation of the quality of clinical practice guidelines. It has been translated into Chinese and is widely used in guideline formulation and quality evaluation. This article intends to take the comparatively high-quality clinical practice guidelines in the field of esophageal cancer screening in China, i.e. "Expert Consensus on Early Esophageal Cancer and Precancerous Lesion Screening in China (2019, Xinxiang)" as an example, to interpret the use of AGREEⅡ item by item, which might provide a reference for medical and health workers to better understand and use the assessment tool.

[Study on the operation process and construction standard of an esophageal cancer screening cohort study].

One of the most cost-effective measures in cancer prevention on cancer is to advocate to be aware of the disease, consciously changing negative behaviors, and taking the initiative to participate in regular physical checkup programs. Esophageal cancer is one of the malignant tumors accompanied by a heavy disease burden in China. Routine screening, early diagnosis, and treatment are the critical points of preventing and treating the disease. Cohort studies help understand the natural history and risk factors of esophageal cancer and identify high-risk groups of the disease. This paper intends to discuss the construction specifications of the multi-dimensional dynamic follow-up shared cohort for esophageal cancer by studying the risk factors, monitoring, and collecting biological sample information, providing references for developing a standardized and unified screening cohort research procedure, and necessary standards on esophageal cancer in the future.

Phylogenetic diversity contributes more to sediment magnetism than abundance during incubation of iron-reducing sediment from a non-active volcanic lake in Northeast China.

AIM: This study aimed to analyse bacterial community and biomineralization products from Wudalianchi non-active volcanic field and the relationship between magnetization and bacterial community. METHODS AND RESULTS: Eighteen sediment samples obtained from Wenbo Lake, high-throughput sequencing and quantitative PCR (qPCR) were separately employed to investigate the bacterial community composition dynamics and abundance variation of the sediment sample with the highest iron-reducing capacity during incubation. The mineralization products were characterized by transmission electron microscopy, scanning electron microscopy, X-ray diffraction (XRD), Raman spectroscopy, vibrating sample magnetometer (VSM) and variable-temperature magnetism analyses. The results showed that the highest iron reduction rate was 98·06%. Seven phyla were identified as dominant bacterial phyla during the incubation process. Iron-reducing bacteria (FeRB) including Geobacter, Desulfosporosinus and Clostridium were involved in the iron mineralization process. The 16S rDNA copy numbers of sediment decreased quickly and then stayed steady during the incubation. Bacteria with rod-shaped and spheroid species were involved in extracellular iron reduction to produce magnetic particles with massive aggregation and columnar structures on the mineral surface morphologies. The materials produced by the microbial community over the incubation period were sequentially identified as siderite, magnetite and maghemite. The magnetism of the mineral samples gradually increased from 0·31748 to 33·58423 emu g-1 with increased incubation time. The final products showed relatively stable magnetism under 0-400 K. Meanwhile, the saturation magnetization (MS ) of the mineralized substance was tightly associated with bacterial diversity (P < 0·05). CONCLUSIONS: Bacterial community varied during incubation of iron-reducing sediment of volcanic lake. Various iron mineral crystals were in turn formed extracellularly by FeRB. The magnetism of mineralized products was tightly associated with bacterial community. SIGNIFICANCE AND IMPACT OF THE STUDY: These results not only help us to better understand the iron mineralization of FeRB in the volcanic lake sediments but also provide basic information for the future application of FeRB in environmental bioremediation.

[Application of transcriptome sequencing and fusion genes analysis in the diagnosis of myeloid leukemia with normal karyotype].

Objective: To analyze the possible fusion genes with high-throughput transcriptome sequencing in myeloid leukemia patients with normal karyotype. Methods: From May 2017 to January 2019, three cases of myeloid leukemia patients with normal karyotype and negative for common fusion genes from the First Affiliated Hospital of Nanchang University were selected as the research objects. The transcriptome sequencing of bone marrow mononuclear cells was performed by high-throughput gene sequencing technology. Defuse software was used to analyze the gene fusion sequence in the transcriptome data, reverse-transcription polymerase chain reaction (RT-PCR) and Sanger sequencing were used to verify the fusion gene with clear pathological significance. Results: All three patients were diagnosed with myeloid leukemia by clinical manifestations, bone marrow cell morphology, immunology, and histochemical staining. Cytogenetic tests showed normal chromosome karyotypes. Fluorescence in situ hybridization and RT-PCR were used to detect BCR-ABL1, PML-RARA, and other common fusion genes. The results were all negative. Transcriptome sequencing and fusion transcripts analysis revealed that these three patients carried rare fusion genes with clear pathological significance, which included BCR-FGFR1, CPSF6-RARG, and NUP98-RARG, respectively. Conclusion: Transcriptome sequencing can accurately analyze rare but pathologically significant fusion genes that may exist in myeloid leukemia patients with normal karyotypes.

[Quality assessment of global lung cancer screening guidelines and consensus].

Objective: To understand the research progress and quality of lung cancer screening guidelines and consensus in China and abroad, and to provide reference for the formulation of high-quality lung cancer screening guidelines in China. Methods: Databases including PubMed, Medline, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, SinoMed, VIP and Wanfang Data were searched, websites and important references were also searched by hand retrieval. The Appraisal of Guidelines for Research & Evaluation Ⅱ(AGREE Ⅱ) and Reporting Items for Practice Guidelines in Healthcare (RIGHT) were used to assess the quality of newly published or updated guidelines and consensus. Results: A total of 9 guidelines and consensus published between 2015 and 2020 were included in this study, with countries including the United States, China, Canada, Saudi Arabia and South Africa. The field of scope and purpose and clarity of presentation scored relatively high but the rigor of development and applicability scored low. Five guidelines were judged to be A-level, all of which were published abroad, and the remaining four were B-level, including three guidelines and consensus issued by China and 1 guideline issued by South Africa. The report rate of RIGHT were higher in basic information and background, lower in review and quality assurance, funding and declaration and management of interests. There were 5 guidelines with a good level and 4 guidelines and consensus with a moderate level. The best overall quality guidelines were those published by the American College of Chest Physicians in 2018 and by the Canadian Task Force on Preventive Health Care in 2016. Conclusions: The number of countries and institutions that issue lung cancer screening guidelines and consensus had been increasing gradually, but the quality in China remained low. It is necessary to develop high-quality lung cancer screening guidelines suitable for China's national conditions in combination with evidence-based methods to guide practice.

[Application of molecular analysis in differential diagnosis of ovarian adult granulosa cell tumors].

Objective: To investigate the application value of molecular detection in the differential diagnosis of ovarian adult granulosa cell tumors (AGCT) by analyzing FOXL2, AKT1 and DICER1 mutations in these tumors. Methods: A total of 48 cases of ovarian sex cord-stromal tumor (SCST) were selected from July 2012 to June 2019 in Beijing Obstetrics and Gynecology Hospital, including 21 adult granulosa cell tumors (AGCT), 15 fibromas/fibrothecomas, 8 Sertoli-Leydig cell tumors (SLCT) and 4 other types of ovarian SCST. Genomic DNA was extracted from the formalin-fixed paraffin-embedded tissue sections. Polymerase chain reaction amplification for FOXL2, AKT1 and DICER1 genes was performed, followed by sequencing using capillary electrophoresis. Fisher exact test was used to compare the prevalence difference of FOXL2, AKT1 and DICER1 mutations among the groups. P<0.05 was considered significant. Results: Eighteen of the 21 (85.7%) AGCT harbored FOXL2 mutation. Compared with other SCST (13.0%, 3 of 23; including fibromas/fibrothecomas and SLCT), FOXL2 mutation was significantly higher in AGCT (P<0.001). In addition, FOXL2 mutation was also detected in one fibrothecoma, two SLCT and two gynandroblastomas. DICER1 mutation was identified in four of eight SLCT, and these cases were moderately to poorly differentiated. FOXL2 mutation was found in one SLCT with DICER1 mutation. There was no DICER1 mutation in other ovarian SCST. No AKT1 mutation was detected in all the patients. Conclusions: FOXL2 mutation is a highly specific biomarker for adult AGCT and may be helpful to resolve problematic cases. Diagnosis should also be taken into consideration of the clinical and histological features as FOXL2 mutation is also found in other SCST. The detection of DICER1 mutation is helpful for the differential diagnosis of ovarian SLCT. Synchronous DICER1 and FOXL2 mutation in the SLCT has been observed, and its significance needs to be further studied.

Varying levels of serum estradiol do not alter the timing of the early endometrial secretory transformation.

STUDY QUESTION: Do supraphysiologic estradiol (E2) levels in the ranges attained during normal and high response superovulation cycles modify the onset of endometrial secretory transformation? SUMMARY ANSWER: Highly supraphysiologic levels of E2 do not alter the ability of physiologic levels of progesterone (P4) to induce secretory transformation. WHAT IS KNOWN ALREADY: Previous studies have demonstrated that premature P4 elevations during IVF cycles are associated with a decrement in clinical pregnancy rates after fresh embryo transfer due to shifts in the window of implantation (WOI). However, alterations in the onset of secretory transformation may not apply uniformly to all patients. High responders with supraphysiologic E2 levels accompanied by similar subtle increases in P4 have not been shown to have decreased sustained implantation rates. This prospective investigation in which whole-genome transcriptomic and methylomic analysis of the endometrium is performed for individual patients under a range of E2 concentrations brings clarity to a long-debated issue. STUDY DESIGN, SIZE, DURATION: A randomized, prospective and paired trial was conducted in which 10 participants were enrolled and randomized to the order in which they completed three distinct uterine stimulation cycles, each at a specific E2 concentration: physiologic (∼180 pg/ml), moderately supraphysiologic (600-800 pg/ml) or supraphysiologic (2000 pg/ml). Target E2 ranges were selected to mimic those seen in natural, controlled ovarian stimulation and IVF cycles. E2 valerate was administered in order to maintain stable E2 levels for 12 days followed by intramuscular P4 in oil 10 mg/day for two doses, after which an endometrial biopsy was performed. A total of 30 endometrial biopsies were included in a whole-genome transcriptomic and methylomic analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthy volunteers without a history of infertility were included in this study at a single large infertility center. DNA was isolated from the endometrial biopsy specimens and bisulfite sequencing was performed to construct a methylation array. Differential methylation analysis was conducted based on differences in M-values of individuals across treatment groups for each probe as well as carrying out t-tests. RNA was isolated for RNA-Seq analysis and gene expression values were compared using DESeq2. All analyses were performed in a pairwise fashion to compare among the three stimulation cycles within individuals and secondarily to compare all participants in each of the cycles. MAIN RESULTS AND THE ROLE OF CHANCE: The mean peak E2 and P4 levels were 275 pg/ml and 4.17 ng/ml in the physiologic group, 910 pg/ml and 2.69 ng/ml in the moderate group was, and 2043 pg/ml and 2.64 ng/ml in the supraphysiologic group, respectively. Principal component analysis of 834 913 CpG sites was performed on M-values of individuals within the low, moderate and supraphysiologic conditions in a paired approach. There were no differences in genome-wide methylation within participants across E2 groups. A paired analysis revealed that gene expression profiles did not differ within the same individual at each of the three E2 levels. No significant alterations in gene expression as related to endometrial physiology were identified between the low, moderate and supraphysiologic groups in an inter-participant analysis. LIMITATIONS, REASONS FOR CAUTION: Although each participant completed a physiologic cycle in which E2 levels were maintained in a range that would simulate a natural cycle, our findings are limited by lack of an unmedicated control to assess if there was a potential effect from E2V. Additionally, our results were obtained in fertile individuals, who may have a different endometrial response compared to an infertile population. Despite the whole genomic endometrial assessment and rigorous, paired study design, the sample size was limited. WIDER IMPLICATIONS OF THE FINDINGS: Given that the endometrial response to P4 is unaffected by E2 levels in the supraphysiologic range, diminutions in implantation seen in stimulated cycles may result from embryonic-endometrial dyssynchrony following early P4 elevations or slowly blastulating embryos, which occur independently of the magnitude of the E2 rise. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Foundation for Embryonic Competence, Basking Ridge, NJ, USA. Dr E.S. reports consultancy work for The Foundation for Embryonic Competence, Basking Ridge, NJ, USA. The other authors declare no conflict of interests related to this topic. TRIAL REGISTRATION NUMBER: NCT02458404.

Intravitreal conbercept for branch retinal vein occlusion induced macular edema: one initial injection versus three monthly injections.

BACKGROUND: To compare the efficacy of one initial intravitreal injection of conbercept (IVC) versus three monthly IVCs in patients with macular edema (ME) after branch retinal vein occlusion (BRVO). Both options were followed by a pro re nata (PRN) retreatment regimen. METHODS: This study retrospectively investigated and followed 60 patients with acute ME secondary to BRVO for over a year. 30 subjects received one initial injection (1 + PRN group); while, 30 received three monthly injections (3 + PRN group). The functional and anatomic outcomes were assessed during each follow-up. RESULTS: The general characteristics of the 60 subjects were as follows: mean [SD] age, 57.43 [13.06] years; 33 [55%] female; 36 [60%] non-ischemic form. Both groups showed a stable gain in visual acuity (VA) with similar logMAR (mean ± SD) (1 + PRN group 0.308 ± 0.399, 3 + PRN group 0.34 ± 0.352) during the first 12 months. Additionally, both groups exhibited a significant reduction in central foveal thickness (CFT) with no statistically significant difference between them (1 + PRN group 222.1 µm ± 197.1 µm, 3 + PRN group 228.4 µm ± 200.2 µm). Both treatment groups had similar improvements in logMAR and anatomic outcomes over time. The stratified analysis showed that patients with the non-ischemic form and those with the ischemic form had similar improvements in VA (0.346 ± 0.366 VS 0.29 ± 0.39, P = 0.575) during the 12 months follow-ups. The number of injections was lower in the 1 + PRN group (4.0 ± 1.6) than in the 3 + PRN group (4.7 ± 1.3) (P = 0.068). No adverse effects or unexpected safety issues were reported in either group. CONCLUSIONS: Conbercept yielded significant improvements in VA and CFT among patients with BRVO induced ME, independent of their retinal ischemia status. The results showed that the 3 + PRN regimen do not lead to better functional outcomes or lower treatment needs in clinical practice as compared to the 1 + PRN regimen.

[Factors associated with sleep quality during first and second trimester in Chinese pregnant woman].

Objective: To investigate sleep quality in pregnant women during their first and second trimester and to identify risk factors. Methods: Data was from the Chinese Pregnant Women Cohort Study. A total of 3 618 pregnant women were included, with the exclusion 346 women who had missing information. Sociodemographic, health-related behavior, depression and sleep quality information were collected and analyzed. Logistic regression analysis were used to explore the influencing factors of sleep quality in pregnant women. Results: Among the 3 618 pregnant woman 28.2% had poor sleep quality in their first trimester and 28.7% in the second trimester. 15.2% pregnant women had progressively worse sleep and 13.0% had persistently poor sleep had pregnant women were generally suffered from poor sleep quality, difficulty falling asleep, sleep disorders and daily fatigue. Regular diet (OR=0.75, 95%CI: 0.62-0.92) and work (OR=0.84,95%CI: 0.71-0.99) in the first trimester were protective factors of sleep quality in pregnant women. Age ≥30 year old (OR=1.19, 95%CI: 1.03-1.37), passive smoking (OR=1.18, 95%CI: 1.02-1.36) and depression (OR=2.25, 95%CI: 1.95-2.61) in the first trimester were risk factors. Conclusions: The rate of poor sleep quality are high among Chinese pregnant woman during their first and second trimester. The risk factors of sleep quality are multiple. Regular diet and work, reduction of tobacco exposure, alleviation of depression symptom may help improve sleep quality among pregnant women.

Regulation of epithelial mesenchymal transition by the renin-angiotensin system: a role for klotho in renal tubular epithelial cells.

Klotho is a putative aging suppressor gene that is primarily expressed in renal tubular epithelial cells. Its expression has been reported to protect against fibrosis in human chronic kidney disease. However, the roles of klotho in epithelial-mesenchymal transition (EMT) and renal fibrosis are yet to be elucidated. The present study aimed to investigate the putative roles of klotho in angiotensin (Ang) II-induced damage of renal tubular epithelial cells. NRK-52E rat cells were treated with various combinations of Ang II, the Ang-converting enzyme inhibitor fosinopril (Fos) and the Ang II receptor antagonist valsartan (Val). The levels of transforming growth factor (TGF)-ß1, soluble klotho, α-smooth muscle actin (α-SMA) and E-cadherin in NRK-52E culture supernatants were measured using enzyme-linked immunosorbent assays. Furthermore, the mRNA and protein expression of TGF-ß1, klotho, α-SMA and E-cadherin was detected using semiquantitative reverse transcription-polymerase chain reaction, immunocytochemistry and Western blot analysis. The results demonstrated that Ang II inhibited the expression of klotho and E-cadherin, while it upregulated the expression of TGF-ß1 and α-SMA, in NRK52E cells. Fos and/or Val were revealed to enhance klotho and E-cadherin expression, and suppress the expression of TGF-ß1 and α-SMA, compared with the Ang II-only group. Furthermore, a positive linear correlation was detected between the expression of klotho and E-cadherin, while negative linear correlations with klotho expression were detected for TGF-ß1 and α-SMA expression. In conclusion, the expression of klotho was demonstrated to be enhanced following treatment with Fos and Val in Ang II-treated NRK-52E cells. The present results indicate that klotho may be involved in the inhibition of Ang II-induced EMT in renal tubular epithelial cells. Therefore, klotho may serve as a protective factor in renal tubulointerstitial fibrosis and aid the treatment of chronic kidney disease (CKD) patients using precision therapy.

Breast cancer recurrence risk prediction using whole-lesion histogram analysis with diffusion kurtosis imaging.

AIM: To explore the role of whole-lesion histogram analysis on diffusion kurtosis imaging (DKI) for predicting breast cancer 21-gene expression profiles and recurrence scores (RSs). MATERIALS AND METHODS: This retrospective study was approved by the institutional review board, and informed consent was waived. Seventy-two patients with breast cancer, who underwent genomic testing and DKI (b values: 0-2,800 s/mm2) were enrolled. Patients were divided into low-, intermediate-, and high-RS groups based on their genomic testing results. Diffusivity (D), kurtosis (K), total apparent diffusion coefficient (Total ADC), and ADC0-700 histogram parameters were calculated. Student's t-test, Wilcoxon signed-rank test, Jonckheere-Terpstra test, receiver operating characteristic curves, and Spearman's correlation were used for the statistical analysis. RESULTS: Total ADC mean/30%/50%/70%, D mean/50%, K mean/30%/50%/70% showed significant differences among the low-, intermediate-, and high-RS groups (p ≤ 0.001, respectively). K50% had the strongest correlation with RSs (correlation coefficient, CC: 0.55). Furthermore, K50% was also correlated with the expression of gene PR, BCL2 and CEGP1 (CC: 0.45, -0.41, -0.41). CONCLUSIONS: Whole-lesion histogram analysis of DKI parameters can be a useful tool for RS prediction of breast cancer. K50% was found to be the most promising parameter for RS prediction.

[The relationship between acid reflux and esophageal motility, esophagitis and cardiac morphology in gastroesophageal reflux disease].

Objective: To analyze the relationship between the severity of esophageal acid reflux and esophageal motility, esophageal mucosal injury and morphological anatomy of gastroesophageal junction (GEJ) in patients with gastroesophageal reflux disease (GERD). Methods: The clinicaldata of GERD patients who underwent 24 h pH-impedance monitoring, gastroscopy and high-resolution manometry (HRM) from January 2016 to January 2019 in the Gastroesophageal Surgery Department of PLA Rocket Force Characteristic Medical Center were retrospectively analyzed. The patients were divided into non-pathological acid reflux group, mild pathological acid reflux group and moderate to severe pathological acid reflux group according to the DeMeester score. The gender and age of each group were matched, with 60 cases in each group. Statistical analysiswas performed to analyze thedifferences in upper esophageal sphincter pressure, lower esophageal sphincter pressure (LES), LES length, length of ventral LES, percentage of ineffective swallowing, esophagitis, Hill grade of GEJ, and hiatus hernia (HH) in each group. The comparison and correlation analysis are also carried out between the groups. Results: The male-female ratio was 33/27, and the age was (57±13) years in each group. Non-parametric analysis showed that the LES pressure and the length of the ventral LES decreased with the severity of acid reflux, and there was a statistical difference (P= 0.033, P=0.015). The detection rate of HH by HRM increased significantly (χ(2)=0.001) as well. Esophagitis score increased with the severity of acid reflux and there was statistical difference (P<0.001).The detection rate of esophagitis increased significantly (χ(2)<0.001) as well. Hill grading score of GEJ increased with the severity of acid reflux, and there was statistical difference (P<0.001).The detection rate of HH by endoscopy increased significantly (χ(2)<0.001) as well. The correlation between DeMeester score and LES pressure, length of ventral LES, percentage of ineffective swallowing, esophagitis score, and Hill grade score were statistically significant (P<0.05). Conclusions: The esophageal low motility (such as low LES pressure) and anatomical abnormalities (abdominal esophageal shortening, GEJ flabbiness, and even HH formation) of the GEJ regionare significantly associated with the severity of acid reflux. These factors may be important causes of increased acid reflux. In addition, the aggravation of acid reflux can also increase the incidence and severity of esophagitis.

[Risk factors for preterm birth, low birth weight and small for gestational age: a prospective cohort study].

Objective: To study the relationship between exposure factors in early pregnancy and preterm birth (PB), low birth weight (LBW) and small for gestational age (SGA) of neonates. Methods: A total of 3 172 pregnant women who were enrolled in the project of Chinese Pregnant Women Cohort Study-Peking Union Medical College (CPWCS-PUMC) from July 25, 2017 to July 24, 2018 and delivered before December 31, 2018 were selected as subjects in this study. The relationship between exposure factors in early pregnancy and adverse outcomes of neonatal delivery was analyzed by using binary logistic regression analysis. Results: The incidence rates of PB, LBW and SGA were 4.76%, 3.53% and 5.74%, respectively. In terms of PB, the analysis results showed that the gestational weight gain (GWG) and living in northern China were protective factors, while premature rupture of membranes, gestational hypertension, dental examination or treatment within 1-3 years and family with 3-4 members were risk factors. In the respect of LBW, GWG and daily consumption of milk and dairy products were the protective factors, while premature rupture of membranes, gestational hypertension, sedentary working time more than 6 hours, dental examination or treatment within 1-3 years and passive smoking were risk factors. For SGA, baby girl, passive smoking, peanut oil consumption and unsalted taste were risk factors, while folic acid supplementation was protective factor. Conclusion: The risk factors for PB, LBW and SGA were multifactorial, and relevant specific measures should be taken to reduce the occurrence of adverse neonatal outcomes.

[Clinicopathological features of ovarian Brenner tumors].

Objective: To investigate the clinicopathological characteristics and diagnosis of ovarian Brenner tumors. Methods: Forty-seven cases of ovarian Brenner tumors were enrolled from January 2012 to May 2018 at Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Clinical data, imaging examination, histopathological characteristics and immunohistochemical phenotype were analyzed. Results: The age of the patients ranged from 30-73 years and the mean age was 55 years. Thirty-nine patients (83.0%) were postmenopausal. Forty cases (85.1%) of the Brenner tumors were benign, five (10.6%) borderline and two (4.3%) malignant. Usual tumor markers of ovarian carcinoma, including CA199 and CA125 were normal or mild elevated in the 47 cases. Imaging before surgery was not specific to Brenner tumors. Microscopically, benign Brenner tumors were composed of nests of bland, transitional-type cells within a fibromatous stroma. In our 5 cases of borderline Brenner tumors, mildly atypical transitional-type cells were projected into the cyst lumens and lack of stromal invasion. In 2 cases of malignant Brenner tumors, different degrees of nuclear atypial transitional-type cells exhibited stromal invasion. Immunohistochemical stains for CK7, GATA3, p63 and CK5/6 were positive in all cases. Ki-67 was less than 5% in Brenner tumors, and up to 20%-30% in malignant Brenner tumors. Conclusion: Brenner tumors are mostly seen in postmenopausal patients and are usually benign. Imaging examination and usual ovarian tumor markers do not provide diagnostic value. Diagnosis and classification of Brenner tumors depend on histopathological evaluation.

[IDH、TERT and 1p/19q predicting clinical outcomes in patients with anaplastic oligodendroglioma].

Objective: To investigate the prognostic values of IDH, TERT and 1p/19q in patients with anaplastic oligodendroglioma. Methods: In the study, 66 patients with pathological diagnosis of anaplastic oligodendroglioma were enrolled (The First Affiliated Hospital of Zhengzhou University 2011 to 2016 years). Kaplan-Meier method was used to calculate the survival rates. Log-rank was used to calculate the differences in group. Chi-square testwas used tocalculate the differences in common factor group. Cox regression model was used to conduct multivariate analysis. Results: The median survival time of IDH-wt and IDH-mt subgroups were 16.10 and 42.00 months with statistical significance (P=0.001). The median survival time of 1p/19q codeleted and 1p/19q noncodeleted subgroups were 42.00 and 22.40 months with statistical significance (P=0.012). IDH-mt and 1p/19q codeleted predicted better survivals compared with IDH-wt and 1p/19q noncodeleted (P=0.001). And IDH-mt and 1p/19q noncodeleted predicted better survivals compared with IDH-wt and 1p/19q noncodeleted (P=0.041), too. Multivariate survival analysis demonstrated that Molecular groups was an independent factor to evaluate the prognosis of anaplastic oligodendroglioma (P=0.008). Conclusion: IDH-mtand (or) 1p/19q codeletedpredicted better survivals in patients with anaplastic oligodendroglioma. IDH and 1p/19q deleted might be a biomarker for predicting prognosis of patients with anaplastic oligodendroglioma.