[Ultrasonographic features of thyroid carcinoma of different sizes: comparison between medullary thyroid carcinomas and papillary thyroid carcinomas].

Objective: To investigate the ultrasonographic features of medullary thyroid carcinomas (MTCs) of different sizes and supply valid information for separating MTCs from papillary thyroid carcinomas (PTCs). Methods: There were 87 patients with MTC and 220 patients with PTC detected by ultrasonography and confirmed by pathology at Tianjin Medical University Cancer Institute and Hospital from June 2018 to March 2022. Nodules were divided into the large nodule group (the maximum diameter of the tumor was＞1 cm) and the small nodule group (the maximum diameter of the tumor was ≤1 cm). There were 97 cases in the small nodule group, including 28 cases of MTC and 69 cases of PTC. There were 210 cases in the large nodule group, including 59 cases of MTC and 151 cases of PTC. After stratification by thyroid nodules, ultrasonographic features of thyroid nodules and metastatic lymph nodes, preoperative serum calcitonin (CT) and carcinoembryonic antigen (CEA) levels were compared between MTC and PTC patients. Results: In the small nodule group, the proportion of MTCs exhibiting hypoecho, smooth margins, and having blood flow signals was higher than that of PTCs, with statistically significant differences (all P＜0.05). In the large nodule group, the proportion of MTCs showing cystic solidity, hypoecho, smooth margins, blood flow, and the type Ⅳvascular distribution was higher than PTCs, and the difference of calcification type between them was also statistically significant (all P＜0.05). In contrast, the differences in the number of lesions and aspect ratio between MTCs and PTCs were not statistically significant regardless of nodule size (all P＞0.05). In the small nodule group,6 metastatic lymph nodes of medullary thyroid carcinoma (LNM-MTC) and 11 metastatic lymph nodes of papillary thyroid carcinoma (LNM-PTC) were correctly diagnosed by ultrasound, respectively. The diagnostic compliance rate of ultrasound was 78.6% (22/28) and 78.3% (54/69), respectively, with no statistically significant difference (P=0.973). In the large nodule group, 28 LNM-MTC and 11 LNM-PTC were correctly diagnosed by ultrasound, respectively. The diagnostic compliance of ultrasound was 88.1% (52/59) and 73.5% (111/151), respectively, which was statistically significant (P=0.022). Among them, 82.1% of LNM-MTC and 56.6% of LNM-PTC showed abnormal blood flow signals, with a statistically significant difference (P=0.016). There were significant differences in preoperative serum CT and CEA levels of different sizes of MTCs (all P＜0.05). Conclusions: Different sizes of MTCs require diverse demonstrative criteria. Abnormal blood flow signal is of great significance in the diagnosis of LNM-MTC. Within the absence of ultrasonic characteristics, preoperative serum CT test can provide confidence for the diagnosis of MTC.

[Correlation of MYB/NFIB gene fusion with the grade and prognosis of head and neck adenoid cystic carcinoma and the concordance of two detection methods].

Objective: To explore the correlation between MYB/NFIB gene fusion and clinicopathological features such as tumor grade and prognosis of head and neck adenoid cystic carcinoma (ACC), and to assess the concordant rate of fluorescent in situ hybridization (FISH) with MYB and NFIB immunohistochemistry. Methods: FISH detection of MYB/NFIB gene fusion was performed on 48 head and neck ACC cases and 15 non-ACC salivary gland tumors at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China during April 2014 and January 2020. ACC cases were divided into grade Ⅰ-Ⅱ, grade Ⅲ and high-grade transformation, according to pathological grading criteria. Prognosis, FISH results and other clinicopathological characteristics were analyzed. MYB and NFIB immunohistochemistry was performed on the 48 ACC and 15 non-ACC cases. The diagnostic accuracy of FISH and immunohistochemistry was compared. Results: FISH detected MYB/NFIB gene fusion in 41.7% (20/48) of the ACC. Its positive rate was inversely correlated with higher pathological grades (P=0.036). The higher histological grade was linked to worse progression-free survival (P=0.024), whereas there was no correlation between the status of gene fusion detected by FISH and progression-free survival (P=0.536). FISH didnot detect MYB/NFIB gene fusion in 15 non-ACC salivary gland tumors The specificity of diagnosing ACC is 100% for both FISH detection of gene fusion and immunohistochemical detection of MYB expression. However, the sensitivity for both methods was only about 41.7%, respectively. By combining FISH and MYB immunohistochemistry, the sensitivity for diagnosing ACC was increased to 66.7%. Conclusions: MYB/NFIB gene fusion has a lower detection rate in grade Ⅲ ACC and high-grade transformation ACC. Meanwhile gene fusion status is not correlated with prognosis. The sensitivity for diagnosing ACC can be improved by combining FISH and MYB immunohistochemistry.

[Pathological characteristics and clinical prognosis of nodular sclerosis grade 2 of classic Hodgkin's lymphoma].

Objective: To investigate the pathological characteristics and clinical prognosis of nodular sclerosis grade 2 of classic Hodgkin's lymphoma (cHL-NS2) in our cancer center. Methods: A retrospective collection of 23 cases of cHL-NS2 admitted in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from July 2008 to April 2019 was performed. Fifty-five cases of nodular sclerosis grade 1 of classical Hodgkin's lymphoma (cHL-NS1) during the same period were selected as control group. Survival curves were plotted using the Kaplan-Meier method, and Cox regression model was used to analyze the influencing factors for survival. Results: The median age of 23 cases of cHL-NS2 was 30 years old. Five cases had extra nodal invasion, and 19 cases were Ⅰ-Ⅱ stage based on Ann Arbor system. The pathological morphology of cHL-NS2 showed that the lymph node structure was completely destroyed and was divided into nodules by thick collagen. The tumor cells in the nodules were abundant and proliferated in sheets. The boundaries between the tumor cells were not clear. The incidence of tumor necrosis in cHL-NS2 was 43.5% (10/23), which was significantly higher than 18.2% (10/55) in cHL-NS1 (P=0.040). The 3-year progression-free survival (PFS) rate of patients in the cHL-NS2 group was 58.1%, which was significantly lower than 89.7% in the cHL-NS1 group (P=0.002). In all of 78 cases, the 3-year PFS rate of patients who did not obtain complete response (CR) was 67.1%, which was significantly lower than 92.2% in patients who achieved CR (P=0.030). Multivariate Cox regression analysis demonstrated that both cHL-NS2 and failure to obtain CR by first-line treatment were independent indicators for short PFS time (P<0.05). Conclusions: In cHL-NS2, the morphology of tumor cells are diverse, and tumor necrosis can be easily found. Under the current first-line treatments of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), cHL-NS2 is an independent indicator for worse PFS.

[Clinicopathological and ultrasound characteristics of extranodal extension in metastatic papillary thyroid carcinoma patients].

Objective: To explore clinicopathological and ultrasound characteristics of extranodal extension in metastatic papillary thyroid carcinoma patients. Methods: 176 patients with papillary thyroid carcinoma who were diagnosed in Tianjin Medical University Cancer Institute and Hospital between March 2011 and March 2016 were identified and recruited in the study. Among the 176 patients, 59 patients were diagnosed with regional lymph nodes metastasis accompanied with extranodal extension (extranodal extension positive group), 117 patients were regional lymph nodes metastasis without extranodal extension (extranodal extension negative group). The clinicopathological and ultrasound characteristics between extranodal extension positive group and extranodal extension negative group were also discussed in this article. Results: 59 patients were diagnosed with regional lymph nodes metastasis accompanied with extranodal extension (extranodal extension positive group). Single lymph node region of extranodal extension was identified in 40 patients, while 19 patients were confirmed with more than 2 regions of extranodal extension. The most frequent extranodal extension were detected in region Ⅵ lymph nodes(32 cases), following by Ⅲ(25 cases), Ⅳ(16 cases), Ⅱ(11 cases). In the aspect of ultrasound characteristics, metastatic papillary thyroid carcinoma with extranodal extension showed a higher incidence of node matting[13.6%(8/59) vs 3.4%(4/117), P=0.022], micro-calcification[66.1%(39/59) vs 46.2%(54/117), P=0.016], cystic[28.8%(17/59) vs 12.8%(15/117), P=0.013], aspect ratio(L/S)<2[88.1%(52/59) vs 75.2%(88/117), P=0.032] and larger diameter(1.95±1.01 cm vs 1.63±0.94 cm, P=0.028). Logistic multivariate analysis demonstrated that node matting (P=0.025) and cystic (P=0.026) were independent risk factors for extranodal extension. Conclusion: Node matting, micro-calcification, cystic, aspect(L/T)>2 and larger diameter were associated with extranodal extension in metastatic papillary thyroid carcinoma patients, especially node matting and cystic, which might help topre-operative ultrasound diagnosis of extranodal extension.

Risk prediction models for delirium in the intensive care unit after cardiac surgery: a systematic review and independent external validation.

Numerous risk prediction models are available for predicting delirium after cardiac surgery, but few have been directly compared with one another or been validated in an independent data set. We conducted a systematic review to identify validated risk prediction models of delirium (using the Confusion Assessment Method-Intensive Care Unit tool) after cardiac surgery and assessed the transportability of the risk prediction models on a prospective cohort of 600 consecutive patients undergoing cardiac surgery at a university hospital in Hong Kong from July 2013 to July 2015. The discrimination (c-statistic), calibration (GiViTI calibration belt), and clinical usefulness (decision curve analysis) of the risk prediction models were examined in a stepwise manner. Three published high-quality intensive care unit delirium risk prediction models (n=5939) were identified: Katznelson, the original PRE-DELIRIC, and the international recalibrated PRE-DELIRIC model. Delirium occurred in 83 patients (13.8%, 95% CI: 11.2-16.9%). After updating the intercept and regression coefficients in the Katznelson model, there was fair discrimination (0.62, 95% CI: 0.58-0.66) and good calibration. As the original PRE-DELIRIC model was already validated externally and recalibrated in six countries, we performed a logistic calibration on the recalibrated model and found acceptable discrimination (0.75, 95% CI: 0.72-0.79) and good calibration. Decision curve analysis demonstrated that the recalibrated PRE-DELIRIC risk model was marginally more clinically useful than the Katznelson model. Current models predict delirium risk in the intensive care unit after cardiac surgery with only fair to moderate accuracy and are insufficient for routine clinical use.

[Evaluation of neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in children of obstructive sleep apnea hypopnea syndrome].

Objective:To evaluate neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in children of obstructive sleep apnea hypopnea syndrome (OSAHS). Method:122 cases of OSAHS patients were selected, and divided into 3 groups： mild OSAHS group (41 cases), moderate OSAHS group (41 cases), and severe OSAHS group （40 cases）, according to the stage apnea hypoventilation index (AHI) and the lowest oxygen saturation (LSaO2). In addition, 40 cases healthy children were selected as control group. The differences NLR and PLR between 4 groups were compared. Result:The NLR in the severe OSAHS group (1.57±0.58) was significantly higher than that in the normal control group (0.98±0.22), mild OSAHS group (1.24±0.47), and moderate OSAHS group (1.36±0.46), P<0.05. However, there was no significant difference in PLR between the normal control group and other OSAHS groups (P> 0.05). A positive correlation between AHI and NLR (r=0.385,P=0.000), and a negative correlation between AHI and minimal oxygen saturation were observed (r=-0.686,P=0.000). Conclusion:NLR might be used as a marker to evaluate the severity of inflammatory status in OSAHS patients, but PLR could no.

Relationship between 5-HTTLPR polymorphism and post-stroke depression.

Post-stroke depression (PSD) is a mental illness characterized by subjective feelings of depression, cognitive dysfunction, and decreased interest. The serotoninergic system is involved in the pathogenesis of depressive disorders and is regulated by the serotonin transporter gene. The serotonin transporter-linked polymorphic region (5-HTTLPR) has been examined as a factor associated with depression and other mental disorders. This study was performed to explore the relationship between 5-HTTLPR and PSD in a Han Chinese population. In total, 199 patients with PSD and 202 unrelated non-PSD patients were recruited from psychiatric hospitals. Depression was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition. Blood samples were collected from all patients for 5-HTTLPR genotyping. Genotype and allele frequencies were compared between the two groups. SS genotype frequency was significantly higher in the PSD group than in the non-PSD group. LL genotype frequency was significantly higher in the non-PSD group than in the PSD group (P < 0.01). This study describes a positive association between 5-HTTLPR and PSD in a Han Chinese population and provides genetic evidence to support the genetic susceptibility of PSD.

Fine mapping of Ath6, a quantitative trait locus for atherosclerosis in mice.

Ath6 is a novel quantitative trait locus associated with differences in susceptibility to atherosclerosis between C57BL/6J (B6) and C57BLKS/J (BKS) inbred mouse strains. Combining data from an intercross and a backcross (1593 meioses) between mice from B6 and BKS strains and from The Jackson Laboratory interspecific backcross panels, (C57BL/6J x Mus spretus) F1 x C57BL/6J and (C57BL/6J x SPRET/Ei) F1 x SPRET/Ei, we constructed a consensus genetic map and narrowed Ath6 to a 1.07 +/- 0.26 cM interval between the anonymous DNA marker D12Pgn4 and the gene Nmyc1. This region is near the proximal end of murine Chromosome (Chr) 12, which is homologous to the human chromosomal region 2p24-p25. Marker order in the Ath6 region was concordant among the two crosses and The Jackson Laboratory interspecific backcross panels. This high resolution map rules out candidate genes encoding apolipoprotein B, syndecan 1, and Adam17. The two Ath6 crosses have a combined potential resolution of 0.06 cM.

Quantitative trait loci mapping for cholesterol gallstones in AKR/J and C57L/J strains of mice.

Quantitative trait locus (QTL) mapping was used to locate genes that determine the difference in cholesterol gallstone disease between the gallstone-susceptible strain C57L/J and the gallstone-resistant strain AKR/J. Gallstone weight was determined in 231 male (AKR x C57L) F(1) x AKR backcross mice fed a lithogenic diet containing 1% cholesterol, 0.5% cholic acid, and 15% butterfat for 8 wk. Mice having no stones and mice having the largest stones were genotyped at approximately 20-cM intervals to find the loci determining cholesterol gallstone formation. The major locus, Lith1, mapped near D2Mit56 and was confirmed by constructing a congenic strain, AK. L-Lith1(s). Another locus, Lith2, mapped near D19Mit58 and was also confirmed by constructing a congenic strain AK.L-Lith2(s). Other suggestive, but not statistically significant, loci mapped to chromosomes 6, 7, 8, 10, and X. The identification of these Lith genes will elucidate the pathophysiology of cholesterol gallstone formation.

Quantitative trait loci analysis for the differences in susceptibility to atherosclerosis and diabetes between inbred mouse strains C57BL/6J and C57BLKS/J.

Mice from the inbred strain C57BLKS/J (BKS) exhibit increased susceptibility to both diabetes and atherosclerosis compared to C57BL/6J (B6) mice. To determine whether the differences in diabetes and atherosclerosis are related, we carried out a cross between B6-db/db and BKS. We selected 99 female F2-db/db progeny, tested the progeny for plasma lipids, plasma glucose, and fatty-streak lesions, and used quantitative trait loci (QTL) analysis to identify the chromosomal regions associated with these phenotypes. No major QTL were found for total cholesterol, VLDL-cholesterol, or triglycerides. Two suggestive QTL were found for HDL-cholesterol (LOD scores of 2. 7 and 2.8), and two suggestive loci were found for plasma glucose (LOD scores of 2.3 and 2.0). Lesion size was not correlated with plasma lipid levels or glucose. Lesion size was determined by a locus at D12Mit49 with a LOD score of 2.5 and a significant likelihood ratio statistic. The gene for apolipoprotein apoB lies within the region, but apoB levels were similar in strains B6 and BKS. The QTL on Chr 12 was confirmed by constructing a congenic strain with BKS alleles in the QTL region on a B6 genetic background. We conclude that susceptibilities to diabetes and atherosclerosis are not conferred by the same genes in these strains and that a major gene on Chr 12, which we name Ath6, determines the difference in atherosclerosis susceptibility.

Physical and genetic mapping of novel microsatellite polymorphisms on human chromosome 19.

We describe here the identification of 11 novel microsatellite polymorphisms on human chromosome 19. These dinucleotide repeat polymorphisms were detected in chromosome 19-specific cosmids that were physically mapped by fluorescence in situ hybridization. For each repeat, flanking oligonucleotide primers were synthesized and the polymerase chain reaction assay was performed on a panel of 100 unrelated individuals to determine the heterozygosity and allele frequencies. To characterize these markers further, genetic and radiation hybrid maps were constructed. These microsatellite polymorphisms will be valuable in further linkage analysis of inherited diseases on chromosome 19p.

Strain distribution pattern for SSLP markers in the SWXJ recombinant inbred strain set: chromosomes 1 to 6.

We typed 147 simple sequence length polymorphisms in the SWXJ recombinant inbred (RI) strain set spanning Chromosomes (Chrs) 1-6. The strain distribution pattern for these loci was combined with data from 18 previously typed loci for SWXJ, resulting in new chromosome maps for this RI set, with an average density of 3.5 cM between loci. This is the first systematic effort to develop a more highly resolved genetic map for the SWXJ RI set and thereby improves the usefulness of this genetic tool for mapping genes underlying both simple and complex genetic disorders.

Strain distribution pattern in AXB and BXA recombinant inbred strains for loci on murine chromosomes 10, 13, 17, and 18.

Strain distribution patterns (SDPs) of selected loci previously mapped to murine Chromosomes (Chrs) 10, 13, 17, and 18 are reported for the AXB, BXA recombinant inbred (RI) strain set derived from the progenitor strains A/J (A) and C57BL/6J (B). The loci included the simple sequence length polymorphisms (D10Nds1, D10Mit2, D10Mit10, D10Mit14, D13Mit3, D13Nds1, D13Mit10, D13Mit13, D13Mit7, D13Mit11, D17Mit18, D17Mit10, D17Mit20, D17Mit3, D17Mit2, D18Mit17, D18Mit9, and D18Mit4), the restriction fragment length polymorphisms Pdea and Csfmr, and the biochemical marker AS-1. These loci were chosen because they map to genomic regions that had few or no genetic markers in the AXB, BXA RI set. Several of these loci also were typed in backcross progeny of matings of the (AXB)F1 to strain A or B. The strain distribution patterns for chromosomes 10, 13, 17, and 18 are reported, and the gene order and map distances determined from the backcross data. The addition of these markers to the AXB, BXA RI strain set increases the genomic region over which linkage for new markers can be detected.

The AXB and BXA set of recombinant inbred mouse strains.

The recombinant inbred (RI) set of strains, AXB and BXA, derived from C57BL/6J and A/J, originally constructed and maintained at the University of California/San Diego, have been imported into The Jackson Laboratory and are now in the 29th to 59th generation of brother-sister matings. Genetic quality control testing with 45 proviral and 11 biochemical markers previously typed in this RI set indicated that five strains had been genetically contaminated sometime in the past, so these strains have been discarded. The correct and complete strain distribution patterns for 56 genetic markers are reported for the remaining RI strain set, which consists of 31 living strains and 8 extinct strains for which DNA is available. Two additional strains, AXB 12 and BXA 17, are living and may be added to the set pending further tests of genetic purity. The progenitors of this RI set differ in susceptibility to 27 infectious diseases as well as atherosclerosis, obesity, diabetes, cancer, cleft palate, and hydrocephalus. Thus, the AXB and BXA set of RI strains will be useful in the genetic analysis of several complex diseases.