[Preliminary study on the relationship between biological rhythm changes and pregnancy complications during pregnancy].

To study the characteristics of heart rate rhythm in pregnant women at different trimester of pregnancy, and to explore the relationship between the basic rhythm of heart rate and pregnancy complications. Thirteen pregnant women who were diagnosed with normal early pregnancy in the Reproductive Center of the Second Affiliated Hospital of Soochow University from June 2018 to December 2019 were prospectively selected. Personal files were created and the heart rate data of pregnancy women was collected 24 hours a day by wearable devices until delivery. Prenatal examination and pregnancy outcomes were surveyed at follow-up. The cosine analysis method and the designed statistical module were used to analyze the long-term rhythm of pregnant women's heart rate. The heart rate of pregnant women showed a significant rhythm at different gestational weeks. Compared with the gestational week of 12, the midline-estimating statistic of rhythm(MESOR) increased significantly at the gestational week of 28 and 32 (t=-2.751,P=0.013;t=-2.314,P=0.032).The phase of rhythm shifted from 14∶00 pm in the first trimester of pregnancy (12 weeks) to 16∶00 pm in the second trimester (24 weeks) (t=2.613,P=0.018) and returned to 14∶00 pm at the third trimester (32 weeks) (t=-2.176,P=0.046). Season had no significant effect on the changes of MESOR, amplitude and phase of maternal heart rate in the first trimester (t=-0.356,P=0.729;t=-0.777,P=0.464;t=-0.434,P=0.673), while season had no significant effect on the changes of MESOR, amplitude and phase in the third trimester (t=-0.663,P=0.532;t=-0.209,P=0.841;t=0.625,P=0.592). The heart rate of one pregnant woman with natural delivery had rhythm disorder from the start of labor to delivery. The heart rate of one pregnant woman with premature rupture of membranes showed rhythm disorder before and after the rupture of membranes, and smaller amplitude. Rhythm disturbance may play a suggestive role in preterm delivery and labor initiation. In conclusion, pregnancy may cause changes in the internal heart rate rhythm. Maternal internal rhythm disturbance may occur when delivery or premature rupture of membranes occurs. The heart rate rhythm of pregnant women may be related to some common complications of pregnancy such as premature rupture of membranes.

[HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems].

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.

[A real-world study of the effects of endocrine therapy on liver function in breast cancer].

Objective: To compare the effect of different endocrine therapy drugs on liver function in patients with early breast cancer. Methods: A retrospective cohort study was conducted to include 4 318 patients with early breast cancer who received adjuvant endocrine therapy in Department of Breast Surgery, Peking Union Medical College Hospital from January 1, 2013 to December 31, 2021. All the patients were female, aged (51.2±11.3) years (range: 20 to 87 years), including 1 182 patients in the anastrozole group, 592 patients in the letrozole group, 332 patients in the exemestane group, and 2 212 patients in the toremifene group. The mixed effect model was used to analyze and compare the liver function levels of patients at baseline, 6, 12, 18, 24, 36, 48, 60 months of medication, and 1 year after drug withdrawal among the three aromatase inhibitors (anastrozole, letrozole, exemestane) and toremifene. Results: ALT and AST of the 4 groups were significantly higher than the baseline level at 6 months (all P<0.01), and there were no significant differences in total bilirubin, direct bilirubin and AST levels among all groups one year after drug withdrawal (P: 0.538, 0.718, 0.061, respectively). There was no significant difference in the effect of all groups on AST levels (F=2.474, P=0.061), and in the effect of three aromatase inhibitors (anastrozole, letrozole, and exemestane) on ALT levels (anastrozole vs. letrozole, P=0.182; anastrozole vs. exemestane, P=0.535; letrozole vs. exemestane, P=0.862). Anastrozole and letrozole had significantly higher effects on ALT levels than toremifene (P<0.01, P=0.009). The proportion of abnormal liver function in each group increased significantly at 6 months compared with baseline, and then the proportion showed a decreasing trend over time. Conclusions: Three aromatase inhibitors (anastrozole, letrozole, and exemestane) and toremifene can significantly increase the level of ALT and AST in patients with breast cancer, and the levels can gradually recover to the baseline after 1 year of drug withdrawal. The effect of non-steroidal aromatase inhibitors (anastrozole, letrozole) on ALT levels is greater than toremifene.

[Alteration of Wnt3a overexpression and its early monitoring value during hepatocellular carcinogenesis].

Objective: To investigate the dynamic expression pattern of carcinoembryonic Wnt3a and its early monitoring value using a hepatocellular carcinoma model. Methods: Forty-eight Sprague Dawley (SD) rats were fed with pellet feed containing 2-acetylaminofluorene (2-AAF, 0.05%) to induce hepatocarcinogenesis, and control rats were fed a pellet diet. Liver tissue and blood samples were collected every two weeks. Liver tissues were pathologically examined using HE staining and grouped. The gene and Wnt3a mRNA expression were analyzed by genome-wide microarray. The expression and distribution of Wnt3a in liver tissue were analyzed by immunohistochemistry. Wnt3a concentration in liver tissue and serum was quantified by enzyme-linked immunosorbent assay. Statistical methods such as χ2 test, Mann-Whitney test and analysis of variance were used to analyze the differences between groups. Results: According to the pathological examination results, the rat livers were divided into four groups: control, hepatocyte degeneration, precancerous lesions and hepatocellular carcinoma. Genome-wide expression profiling analysis and comparison with the control group revealed that 268 and 312 genes were up-regulated and 57 and 201 genes were down-regulated in the precancerous and cancerous group when signal logarithm ratio (SLR) was >8 log2cy5/cy3, and these significantly altered genes mainly involved in cell proliferation, signal transduction, tumor metastasis, and apoptosis. The expression of Wnt3a at mRNA level was significantly increased in all stages of cancer induction, including degeneration group (1.15±0.24, q=8.227), precancerous group (1.85±0.18, q=12.361) and cancerous group (2.59±0.55, q=18.082). Compared with the control group (0.25±0.11, F=121.103, P<0.001), the degeneration group, the precancerous group and the liver cancer group were up-regulated by 4.6, 7.4 and 10.4-folds, respectively. Immunohistochemistry showed that compared with the control group, the positive rate of Wnt3a in the degeneration group was 66.7% (12/18, χ2=10.701, P=0.001), and both the precancerous and liver cancer groups were positive (9/9, χ2=17.115, P<0.001). Wnt3a expression was gradually increased in liver and blood samples during the process of carcinogenesis, and the difference between two groups was statistically significant (F=176.711, P<0.001). Wnt3a overexpression was secreted into blood stream via cancerous liver tissue, and there was a linear correlation between Wnt3a levels in blood and liver samples (r=0.732, P<0.001). Conclusions: Wnt3a overexpression is closely related with hepatocellular carcinogenesis, and thus may become a new monitoring marker.

[Expression of tuftelin protein and its clinical value in HBV-related liver cancer tissues].

Objective: To analyze the expression of tuftelin protein (TUFT1) and its clinical value in hepatocellular carcinoma (HCC)-related liver cancer tissues. Methods: The biological information data of TUFT1 mRNA expression in liver cancer and non-cancer tissues were analyzed from the TCGA and Oncomine database. After the approval of the ethics committee, the self-pairing method was used to collect the postoperative cancer and para-carcinoma tissues of 132 HCC cases hospitalized between January 2009 and December 2014. Tissue microarray and immunohistochemistry (IHC) were used to analyze the expression of TUFT1 in liver tissues. According to IHC staining, liver cancer was divided into high TUFT1 and low/no expression group. Combined with clinical data, the clinicopathological characteristics were statistically analyzed between and within the groups. The 5-year overall survival (OS) and disease-free survival (DFS) was analyzed by correlation analysis. Results: IHC staining showed that TUFT1 in cancer tissue was localized in the cytoplasm and cell membrane, and its positive expression rate was significantly higher in the liver cancer group (87.1%) than the para-carcinoma group (64.4%) (χ (2) = 18.563, P < 0.001). TUFT1 expression intensity in patients with liver cancer was significantly correlated with HBeAg positive (χ (2) = 4.080, P = 0.043), tumor size (χ (2) = 9.388, P = 0.002), vascular invasion (χ (2) = 14.885, P < 0.001), TNM stage (χ (2) = 13.516, P < 0.001) and ascites (χ (2) = 5.940, P = 0.015). TUFT1 high expression was negatively correlated with OS and DFS (P < 0.001). Conclusion: The overexpression of TUFT1 is closely related to HBV replication, vascular invasion and poor prognosis, and it is expected to become a useful marker for liver cancer diagnosis and prognosis.

[A comparative study of breast cancer mass screening and opportunistic screening in Chinese women].

Objective: To compare the population characteristics, the positive rate of screening, the detection rate of breast cancer, early diagnosis rate and the cost between the mass screening group and opportunistic screening group of breast cancer. Methods: This study is a prospective multicenter cohort study conducted from January 1, 2014 to December 31, 2016. The participants were enrolled for mass screening or opportunistic screening of breast cancer. After completing the questionnaire, all the participants received breast physical examination and breast ultrasound examination every year for 3 rounds by year. The participants' characteristics and screening results of the two groups were compared by χ2 test, Fisher exact test or Wilcoxon rank-sum test. Results: A total of 20 080 subjects were enrolled. In the mass screening group, 9 434 (100%), 8 111 (85.98%) and 3 940 (41.76%) cases completed the 3 rounds of screening, and 10 646 (100%), 6 209 (58.32%) and 2 988 (28.07%) cases in the opportunistic screening group, respectively. In the opportunistic screening group, the proportions of less than 3 months lactation (1 275/9 796 vs. 1 061/8 860, χ²=4.597, P=0.032), non-fertility (850/10 646 vs. 574/9 434, χ²=27.400, P<0.01), abortion history (6 384/10 646 vs. 5 062/9 434, χ²=81.232, P<0.01), postmenopausal (2 776/10 646 vs. 2 217/9 434, χ²=17.757, P<0.01), long-term oral contraceptives(>6 months) (171/10 646 vs. 77/9 434, χ²=25.593, P<0.01) and family history of breast cancer in first-degree relatives (464/10 646 vs. 236/9 434, χ²=51.257, P<0.01) were significantly higher than those in mass screening group. The positive rate of screening (514/10 646 vs. 128/9 434, χ²=194.736, P<0.01), the detection rate of breast cancer (158/10 646 vs. 13/9 434, χ²=107.374, P<0.01), and positive rate of biopsy (158/452 vs. 13/87, χ²=13.491, P<0.01) in the opportunistic screening group were significantly higher than those of the mass screening group. The early diagnosis rate of the mass screening group was significantly higher than the opportunistic screening group (10/12 vs. 66/141, χ²=5.902, P=0.015). The average cost for detecting each breast cancer case of the mass screening group was 215 038 CNY, which was 13.6 times of the opportunistic screening group (15 799 CNY/case). In the opportunistic screening group, the positive rate of biopsy in primary hospitals was significantly lower than that in large-volume hospitals (79/267 vs. 79/185, χ²=8.267, P=0.004), but there was no significant difference in the mass screening group (6/37 vs. 7/50, χ²=0.082, P=0.774). Conclusions: Breast cancer screening can improve early detection rate. Compared with the mass screening mode, the opportunistic screening mode has the advantages of higher proportion of high-risk factors, higher positive rate of screening, higher detection rate of breast cancer, higher positive rate of biopsy, and lower cost of screening. However, the early diagnosis rate of breast cancer of opportunistic screening is lower than that of mass screening. The positive rate of opportunistic screening in primary hospitals is lower than that of large-volume hospitals. The two screening modes have their own advantages and should be chosen according to local conditions of different regions in China.

[Hypoxia-inducible factor-1α mediates and regulates angiogenesis-related factors expression in hepatocellular carcinoma].

Objective: To investigate the expression of hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) during the progression of liver diseases and the molecular mechanism of HIF-1α in regulating the expression of angiogenic factors in hepatocellular carcinoma (HCC). Methods: Serum samples from hospitalized patients with liver cancer, liver cirrhosis, and chronic hepatitis were collected, and healthy people were used as controls. Mouse models of hepatocarcinogenesis were used to detect the dynamic expression of HIF-1α, VEGF and Ang-2. Enzyme-linked immunosorbent assay was used to quantitatively analyze the serum levels of HIF-1α, VEGF and Ang-2 in patients with liver disease and mice. HIF-1α-specific miRNA expression plasmids was constructed to transfect HepG2 human HCC cells. HIF-1α mRNA transcriptional interference effects were analyzed on biological behavior, VEGF and Ang-2 expression, and epithelial mesenchymal transformation (EMT) in human HCC cell line. The sample means of multiple groups were compared by analysis of variance and q test and the sample rate was compared by χ (2) test. Results: In patients with chronic liver disease, the serum expression of HIF-1α, VEGF and Ang-2 in the liver cancer group (145.6 ± 32.6) µg/L, (458.9 ± 125.3) µg/L and (42.9 ± 5.1) µg/L was significantly higher than the liver cirrhosis (P < 0.001) (79.5 ± 28.4) µg/L, (206.8 ± 56.8) µg/L and (26.2 ± 6.1) µg/L and chronic hepatitis group (60.1 ± 18.8) µg/L, (178.1 ± 85.4) µg/L and (21.8 ± 6.9) µg/L. In addition, HIF-1α was positively correlated with VEGF (r = 0.937, P < 0.001), HIF-1α and Ang-2 (r = 0.933, P < 0.001), and VEGF and Ang-2 (r = 0.910, P < 0.001). Mouse models of hepatocarcinogenesis confirmed that HIF-1α, VEGF and Ang-2 had progressively increased during the process of malignant transformation from normal hepatocytes, hepatocyte degeneration, and precancerous lesions to canceration. HIF-1α miRNA intervention plasmid had transformed HepG2 cells. Compared with the blank group, HIF-1α mRNA, HIF-1α, VEGF and Ang-2 were decreased by 88.1%, 59.8%, 54.0% and 36.0% at 72h, respectively. The expression level of EMT-related protein Snail (0.26 ± 0.02 and 0.67 ± 0.09, q = 6.75, P < 0.003), VIM (0.27±0.08 and 0.73±0.04, t = 10.35, P < 0.001) and Twist (0.24 ± 0.07 and 0.73 ± 0.02, q = 12.08, P < 0.001) was significantly reduced, but the expression level of E-cadherin (0.76 ± 0.08 and 0.27 ± 0.09, q = 7.05, P < 0.002) was significantly increased. Conclusion: HIF-1α mediates and regulates angiogenesis-related factors such as VEGF and Ang-2 expression in hepatocellular carcinoma. Furthermore, HIF-1α transcriptional interference can significantly affect the biological characteristics and EMT transformation of hepatocellular carcinoma cells.

Advanced age promotes colonic dysfunction and gut-derived lung infection after stroke.

Bacterial infection a leading cause of death among patients with stroke, with elderly patients often presenting with more debilitating outcomes. The findings from our retrospective study, supported by previous clinical reports, showed that increasing age is an early predictor for developing fatal infectious complications after stroke. However, exactly how and why older individuals are more susceptible to infection after stroke remains unclear. Using a mouse model of transient ischaemic stroke, we demonstrate that older mice (>12 months) present with greater spontaneous bacterial lung infections compared to their younger counterparts (7-10 weeks) after stroke. Importantly, we provide evidence that older poststroke mice exhibited elevated intestinal inflammation and disruption in gut barriers critical in maintaining colonic integrity following stroke, including reduced expression of mucin and tight junction proteins. In addition, our data support the notion that the localized pro-inflammatory microenvironment driven by increased tumour necrosis factor-α production in the colon of older mice facilitates the translocation and dissemination of orally inoculated bacteria to the lung following stroke onset. Therefore, findings of this study demonstrate that exacerbated dysfunction of the intestinal barrier in advanced age promotes translocation of gut-derived bacteria and contributes to the increased risk to poststroke bacterial infection.

[Impact of the 21-gene recurrence score assay in clinical treatment and prognosis analysis for patients with hormone receptor positive early-stage breast cancer].

Objective: To explore the association between the 21-gene recurrence score (RS) and clinicopathologic characteristics as well as prognosis in patients with axillary lymph node negative, hormone receptor (HR) positive breast cancer. Methods: The clinicopathologic data of 439 early breast cancer patients who underwent 21 gene RS testing was retrospectively analyzed. According to the 21 gene RS, the patients were divided into low risk (295 cases), intermediate risk (111 cases) and high-risk (33 cases) group. The relationship between the 21 gene RS and clinicopathological characteristics, treatment, recurrence and metastasis was analyzed. Univariate and multivariate statistical analyses were used to analyze the risk factors for relapse free survival (RFS). Results: Tumor grade, estrogen receptor (ER), progesterone receptor (PR) and Ki-67 index were significantly different among the 3 risk cohorts (P<0.001 for all). After a median follow-up of 32 months, the recurrence rate in low risk group (3.7%) was significantly lower than that in the intermediate-high risk group (9.0%), the locoregional recurrence (LRR) rate of low, intermediate and high risk group was 2.4%, 6.3% and 9.1%; and the distant metastasis (DM) rate in low risk group was 1.4% and 2.1% in the intermediate-high risk group. Univariate analysis showed RS, ER status and endocrine therapy were prognostic factors for RFS (P<0.05 for all). Multivariate analysis showed that RS was an independent significant predictor for RFS (P=0.04). Conclusions: The 21-gene RS is related to tumor grade, ER, PR and Ki-67 index. RS is an independent risk factor for RFS in patients with hormone receptor positive early-stage breast cancer.

LncRNA SNHG12 promotes cell growth and inhibits cell apoptosis in colorectal cancer cells.

Several long non-coding RNA (lncRNA) might be correlated with the prognosis of colorectal cancer (CRC) and serve as a diagnostic and prognostic biomarker. However, the exact expression pattern of small nucleolar RNA host gene 12 (SNHG12) in colorectal cancer and its clinical significance remains unclear. The level of SNHG12 was detected by qRT-PCR in CRC tissues and CRC cells. MTT assay and colony formation assay were performed to examine the cell proliferation of CRC cells transfected with pcDNA-SNHG12 or si-SNHG12. Flow cytometry technology was used to detect cell cycle and cell apoptosis of CRC cells transfected with pcDNA-SNHG12 or si-SNHG12. The protein level of cell cycle progression-related molecules, including cyclin-dependent kinases (CDK4, CDK6), cyclin D1 (CCND1) and cell apoptosis-related molecule caspase 3 was detected by western blot. The effect of SNHG12 knockdown was examined in vivo. Increased levels of SNHG12 were observed in CRC tissues and in CRC cells. SNHG12 promoted the cell proliferation of CRC cells. In addition, SNHG12 overexpression boosted the cell cycle progression of SW480 cells transfected with pcDNA-SNHG12 and SNHG12 knockdown inhibited the cell cycle progression of HT29 cells transfected with si-SNHG12. SNHG12 also inhibited the cell apoptosis of CRC cells. We also found that SNHG12 increased the expression of cell cycle-related proteins and suppressed the expression of caspase 3. Our results suggest that SNHG12 promoted cell growth and inhibited cell apoptosis in CRC cells, indicating that SNHG12 might be a useful biomarker for colorectal cancer.

Changes of gene expression profiles across different phases of vascular calcification in rats.

This study investigated the alteration of gene expression profiles in order to gain a deeper understanding into the molecular mechanism involved in different processes of vascular calcification (VC). Sprague Dawley (SD) rats were injected with 300,000 µg/kg vitamin D3 and gavaged with 25 mg/kg nicotine for 8 or 16 weeks to create 8- and 16-week VC calcification groups. Histological analysis and quantification of aortic calcium content were used to determine the severity of vascular calcification. The suppression subtractive hybridization (SSH) method was employed to screen for up and downregulated genes in early and later phases of vascular calcification. Changes in calcium and phosphorus levels in tissue were used as markers of vascular calcification. Quantification of aortic calcium content revealed that vascular calcification might regress over time. In the early phase of vascular calcification, many calcification-promoting genes were upregulated, including ossification, oxidation, and inflammatory genes. In contrast, in later phase of vascular calcification, various calcification-inhibitor genes were highly expressed, including pyrophosphoric acid synthesis genes, glutamate signal peptide-related, reduction activity, and apoptosis regulation genes. The relatively higher expression of calcification-inhibitor genes compared to that of calcification-promoting genes might explain the genetic mechanism leading to the regression of vascular calcification. Therefore, this study provides a genomic basis to facilitate understanding of the molecular mechanism underlying vascular calcification regression.

Correlation between quantitative severity of stress thallium-201 myocardial perfusion defect and severity of coronary stenosis.

The correlation between the quantitative myocardial perfusion defect severity of stress 201Tl single-photon emission computed tomography and the severity of coronary stenosis was investigated in 28 patients with angina pectoris. Among the 28 patients, four had normal or nearly normal coronary angiograms, seven had one-vessel disease, six had two-vessel disease and 11 had three-vessel disease. Seven patients had prior myocardial infarctions and two had collateral flows to the diseased vessels. The quantitative 201Tl defect severity score was obtained by summing the standard deviations of each pixel in which the counts fell > 2.5 SD below the mean normal counts. The severity of coronary stenosis was expressed as the Gensini score. The quantitative 201Tl defect severity score correlated significantly with the Gensini score. In patients without prior myocardial infarction or collateral flow, a more significant correlation between the quantitative 201Tl defect severity score and the Gensini score was found. Quantitative analysis of stress 201Tl defect severity provides a useful, noninvasive assessment of the functional severity of coronary stenosis compared with coronary angiography.

[The immune reconstitution in Scid mice and the effect of T, B, NK cells on the growth potential of CNE-2Z-H5 transplanted tumor].

CNE-2Z-H5 was transplanted into the Scid mice of which immune system was reconstituted with the peripheral lymphocytes or thymus of the isogenetic mice and the BALB/c nude mice of which NK cells were inhibited with cyclophosphamide. The results showed that the growth speed and weight of the tumors were in order from high to low among groups of Scid mice, BALB/c nude mice with NK inhibited, BALB/c nude mice, Scid mice with immune reconstitution. The transplanted tumor, in 6/6 cases injected beforehand with peripheral lymphocytes and 1/3 case transplanted accompanied with thymus disappeared within 22 days. The conclusion is that the immune reconstitution of Scid mice has succeeded and play an effective role in antitumor response.

Diagnosis of coronary artery disease using dipyridamole thallium-201 imaging.

Dipyridamole thallium-201 imaging, using single-photon emission computed tomography, was evaluated for its safety and diagnostic efficacy in 109 patients with angiographically documented coronary artery disease and 35 normal subjects. The most common side effects after the intravenous administration of dipyridamole thallium-201 (0.56 mg/kg) included chest pain in 41 patients, dizziness in 20 patients, headache in 16 patients, and ST segment depression > or = 1 mm in 15 patients. Aminophylline was required to reverse the side-effects in 46 patients, and 45 of the 46 patients experienced complete relief of symptoms. Of the 109 patients with coronary artery disease, 104 had abnormal dipyridamole thallium images. The per patient sensitivity was 95%. Of the 35 normal subjects, 27 had normal thallium images. The per patient specificity was 77%. The sensitivity and specificity for the individual vessels were 84% and 87% for the left anterior descending artery, 67% and 97% for the left circumflex artery, and 89% and 85% for the right coronary artery, respectively. Dipyridamole thallium-201 imaging is a relatively safe noninvasive method and is an effective alternative to exercise thallium-201 scintigraphy for the diagnosis of coronary artery disease.

An unusual cystic lesion histologically similar to autosomal dominant polycystic kidney disease in a child with aniridia and del 11p13.

The association of Wilms tumor with an interstitial deletion on the short arm of chromosome 11 is well established. Specifically, the 11p13 band has been implicated in the syndrome of Wilms tumor, aniridia, genitourinary abnormalities and mental retardation. Only rarely have other renal lesions been associated with the chromosomal abnormality del 11p13. We report a case of a segmental cystic lesion, histologically akin to autosomal dominant polycystic kidney disease, in a child with aniridia and the del (11)(p12p14) karyotype.

The role of Tamm-Horsfall mucoprotein in calcium oxalate crystallization. N-acetylcysteine--a new therapy for calcium oxalate urolithiasis.

OBJECTIVE: To assess the role of Tamm-Horsfall mucoprotein (THM), obtained from normal subjects (nTHM) and stone-formers (sfTHM), on crystallization of calcium oxalate (CaOx) in whole urine, and to assess the effects of N-acetylcysteine (AC) in preventing renal stone formation. MATERIALS AND METHODS: A modified rapid evaporation method was used to test the effects of THM and AC on crystallization of CaOx in vitro. Animal experiments involving 30 rats and a clinical study involving 17 patients with idiopathic CaOx urolithiasis were also performed to identify further the role of AC in preventing CaOx stone formation in vivo. RESULTS: The results showed that the volume of CaOx crystals was greatly reduced, by ultrafiltration, to 39.1% of untreated urine, but increased to 81.4% by adding nTHM (35 mg/l). sfTHM was a more potent promoter. AC was found to inhibit the transformation of THM and lower the crystallization of CaOx both in vitro and in vivo. CONCLUSION: We believe that the transformation of THM is an important step in the formation of urolithiasis. AC might be a new way to prevent renal stone formation and recurrence.

Evidence that the nodulation regulatory gene nodD3 of Rhizobium meliloti is transcribed from two separate promoters.

The Bgl II fragment carried in plasmid pMH903, which covers the nodD3 region of Rhizobium meliloti, has been sequenced. By using both S1 nuclease mapping and primer extension, two transcription start sites were demonstrated in the sequence. After the first transcription start site, there were two open reading frames (ORF) followed by the nodD3 coding sequence which was also preceded by the second promoter. The nodD3 gene under the first promoter mediated high, constitutive expression of nodC-lacZ fusion, and the gene under the second promoter required the product of nodD1 and alfalfa (Medicago sativa) seed exudate for the activation of fusion. Nodulation experiments showed that the nodD3 gene under either promoter was functional in eliciting nodules on alfalfa. The deletion of part of the two ORFs after the first promoter or deletion of the second promoter did not block the constitutive expression of nodC-lacZ fusion, whereas the deletion of the first promoter region or a polar insertion mutation between the two promoters did cause nodD3 to activate nodC only in the presence of the inducer. It indicates that nodD3 can be transcribed from the first promoter as well as from a separate second promoter.

Inadvertent arterial administration of parenteral hyperalimentation solution resulting in generalized seizure activity.

Serious complications may arise from improper central venous catheter placement. In this case report, seizures occurred as a result of inadvertent arterial administration of parenteral hyperalimentation. There is a need for radiographic confirmation of central venous catheter position by qualified personnel before catheter use.

Mechanistic studies of two amino acid racemases of broad substrate specificity from Pseudomonas striata and Aeromonas caviae.

The conversion of L-[alpha-2H]alanine in H2O and unlabeled L-alanine in 2H2O into D-alanine, under nearly irreversible conditions, with the amino acid racemase from Pseudomonas striata showed significant internal transfer of the alpha-hydrogen. This result has been interpreted as being indicative of a single base mechanism for the racemization. The relative rates of deuterium incorporation into unlabeled D- and L-methionine by the two amino acid racemases of broad substrate specificity from P. striata and Aeromonas caviae, were measured in 2H2O. The results showed a markedly different pattern, dependent upon the configuration of the initial substrate; with D-methionine as substrate deuterium is incorporated into both enantiomers at approximately the same rate, but with L-methionine as substrate deuterium is incorporated considerably faster into the D than the L enantiomer. These results argue against a single base mechanism of racemization for these enzymes and are best rationalized in terms of a double base model where only one of the bases undergoes proton (deuterium) exchange with the solvent while the amino acid is enzyme-bound. The interpretation of the earlier experiment needs to be considered in light of these results.