1.Spatial transcriptome analysis of long non-coding RNAs reveals tissue specificity and functional roles in cancer.
Kang XU ; Xiyun JIN ; Ya LUO ; Haozhe ZOU ; Dezhong LV ; Liping WANG ; Limei FU ; Yangyang CAI ; Tingting SHAO ; Yongsheng LI ; Juan XU
Journal of Zhejiang University. Science. B 2023;24(1):15-31
Long non-coding RNAs (lncRNAs) play a significant role in maintaining tissue morphology and functions, and their precise regulatory effectiveness is closely related to expression patterns. However, the spatial expression patterns of lncRNAs in humans are poorly characterized. Here, we constructed five comprehensive transcriptomic atlases of human lncRNAs covering thousands of major tissue samples in normal and disease states. The lncRNA transcriptomes exhibited high consistency within the same tissues across resources, and even higher complexity in specialized tissues. Tissue-elevated (TE) lncRNAs were identified in each resource and robust TE lncRNAs were refined by integrative analysis. We detected 1 to 4684 robust TE lncRNAs across tissues; the highest number was in testis tissue, followed by brain tissue. Functional analyses of TE lncRNAs indicated important roles in corresponding tissue-related pathways. Moreover, we found that the expression features of robust TE lncRNAs made them be effective biomarkers to distinguish tissues; TE lncRNAs also tended to be associated with cancer, and exhibited differential expression or were correlated with patient survival. In summary, spatial classification of lncRNAs is the starting point for elucidating the function of lncRNAs in both maintenance of tissue morphology and progress of tissue-constricted diseases.
Humans
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Gene Expression Profiling
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Neoplasms/genetics*
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Organ Specificity
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RNA, Long Noncoding/genetics*
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Transcriptome
2.Correlations of expressions of tissue inhibitor of matrix metalloproteinase-1 and fibronectin 1 in pregnancy associated breast cancer with expression of E-cadherin and prognosis
Jihai JIN ; Guangrong LIN ; Yujuan LIU ; Limei FU
Cancer Research and Clinic 2023;35(3):179-184
Objective:To investigate the expressions of tissue inhibitor of matrix metalloproteinase-1 (TIMP1) and fibronectin 1 (FN1) in pregnancy associated breast cancer (PABC) and their correlations with expression of E-cadherin (E-cad).Methods:The clinicopathological data of 55 PABC patients in Binzhou People's Hospital Affiliated to Shandong First Medical University from January 2011 to December 2020 were retrospectively analyzed. Immunohistochemistry was used to detect expressions of TIMP1, FN1 and E-cad in cancer tissues and corresponding paracancerous tissues (>3 cm from the edge of the tumor foci). The expressions of TIMP1 and FN1 proteins in fresh intraoperative frozen cancer tissues and paracancerous tissues of 10 PABC patients were detected by Western blotting. The correlations of TIMP1 and FN1 expressions with clinicopathological characteristics of patients were analyzed by χ2 test, the correlation of TIMP1 and FN1 expressions with E-cad expression was analyzed by Spearman method, and the correlation of TIMP1 and FN1 expressions with survival was analyzed by Kaplan-Meier method. Results:The positive rates of TIMP1 and FN1 in PABC tissues were 72.7% (40/55) and 58.2% (32/55), and 25.5% (14/55) and 18.2% (10/55) in paracancerous tissues, and the differences were statistically significant ( χ2 values were 24.59 and 18.64, both P < 0.001). The results of Western blotting showed that the relative expressions of TIMP1 and FN1 proteins in the fresh cancer tissues of 10 PABC patients was higher than those in the corresponding paracancerous tissues (1.60±0.76 vs. 0.62±0.29, 1.31±0.62 vs. 0.44±0.15), and the differences were statistically significant ( t values were 5.92 and 4.86, both P < 0.001). The expressions of TIMP1 and FN1 in PABC tissues were correlated with estrogen receptor expression, Ki-67 positivity index, TNM stage and lymph node metastasis (all P < 0.05). The expressions of TIMP1 and FN1 were negatively correlated with expression of E-cad in PABC ( r values were -0.471 and -0.432, both P < 0.001). Five cases were lost to follow-up, and the remaining 50 cases had a median follow-up time of 43 months (12-90 months). Among the 50 cases, 36 cases were TMP1-positive and 29 cases were FN1-positive. The overall survival of TIMP1-negative group and FN1-negative group were better than those of the corresponding positive group ( χ2 values were 4.49 and 6.06, both P < 0.05); the median overall survival time of TIMP1-positive group and FN1-positive group were 51 months (95% CI 37-65 months) and 43 months (95% CI 32-53 months), while that of TIMP1-negative group and FN1-negative group were 89 months (95% CI 84-93 months) and 87 months (95% CI 85-92 months). Conclusions:TIMP1 and FN1 expressions are elevated in PABC tissues and negatively correlated with E-cad expression, TIMP1 and FN1 may be involved in PABC invasion through epithelial-mesenchymal transition and affect the prognosis of patients.
3.Construction of the standard index system for the outpatient job competency of midwife
Limei LI ; Shulan LI ; Ruining QI ; Mei JIANG ; Lili SONG ; Cuicun HAN ; Weimiao SHI ; Yuhui FU
Chinese Journal of Modern Nursing 2022;28(29):4026-4031
Objective:To construct a standard index system for the outpatient job competency of midwife, and to clarify the midwives' abilities when providing outpatient services, so as to improve the midwives' core competencies and service satisfaction.Methods:A research group was established in December 2018. On the basis of literature review and survey of midwives' outpatient needs in the early stage, referring to expert opinions, and taking job competency theory as the theoretical framework, the standard index system for the outpatient job competency of midwife were initially constructed. From December 2018 to March 2019, convenience sampling was used to select 24 experts from different ClassⅢ Grade A hospitals of Beijing, and the Delphi method was used to conduct 2 rounds of expert consultations.Results:Among 2 rounds of expert consultations, the effective recovery rates of the questionnaires were all 100.0% (24/24) , the positive coefficient of experts was 100.0%, and the coefficient of authority of experts was 0.786. The Kendall coordination coefficients of the 2 rounds of correspondence were 0.030 and 0.400, respectively ( P<0.05) . The final construction of standard index system for the outpatient job competency of midwife included 4 first-level indicators, 9 second-level indicators and 24 third-level indicators of knowledge and skills, professional quality, health education ability, and ability to improve the quality of professional services. Conclusions:The standard index system for the outpatient job competency of midwife is scientific and reasonable, comprehensive in content, and strong in specialty, which can provide a reference for the training and assessment of midwife.
4.Behavior preferences of pregnant women in Quzhou to obtain newborn health information
Hongzhu FU ; Shufen QIU ; Limei YU
Chinese Journal of Modern Nursing 2022;28(4):541-543
Objective:To explore the behavioral preferences of pregnant women in Quzhou to obtain newborn health information, so as to provide a reference for relevant departments to formulate policies.Methods:From January 2020 to April 2021, convenience sampling was used to select 226 pregnant women who gave birth in Quzhou Hospital of Traditional Chinese Medicine as the research object. The self-designed Behavior Preference of Pregnant Women to Obtain Newborn Health Information Questionnaire was used to investigate pregnant women through the form of online return visits. A total of 226 questionnaires were issued, and 215 valid questionnaires were returned with the valid response rate of 95.13%.Results:Among 215 pregnant women, they thought it was difficult to obtain information on the prevention and treatment of common diseases (such as diaper rash, impetigo) , distinguishing and nursing of physiological phenomena (such as jaundice, galactorrhea) , form and content of early education, mental behavior building and premature infant health monitoring. These 215 pregnant women preferred to obtain newborn health information from the WeChat public platform/ application (APP) , brochures/billboards, online teaching and expert consultation.Conclusions:Pregnant women have diverse needs for newborn health information, and they prefer many ways to obtain it. In clinical practice, we should broaden the ways of obtaining specialized information to provide pregnant women with scientific and accurate newborn health information.
5.Detection of epidermal growth factor receptor mutations in non-small cell lung cancer by immunohistochemistry.
Xuemei YU ; Ruiqi MAO ; Min LIU ; Limei FU ; Lifang SHI ; Xinjun LI
Journal of Central South University(Medical Sciences) 2021;46(1):11-17
OBJECTIVES:
To evaluate the sensitivity and specificity of immunohistochemistry (IHC) for detecting common epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) and to estimate the cost-effectiveness of IHC testing.
METHODS:
A total of 208 NSCLC patients were included in the trial, and the EGFR mutation status in the patients were detected by PCR and IHC. Two mutation-specific antibodies against the most common exon 19 deletion (clone SP111) and exon 21 L858R mutation (clone SP125) were tested by using automated immunostainer. A cost-effectiveness analysis model was built for the analysis of optimal detection scheme.
RESULTS:
With a cutoff value of IHC 1+, the overall sensitivity and specificity of the IHC-based method compared with the PCR-based method were 81.7% (95% CI 72.4% to 89.0%) and 94.7% (95% CI 92.6% to 99.5%), respectively. EGFR 19del mutation was detected by SP111 antibody with a sensitivity of 65.9% (95% CI 49.4% to 79.9%) and specificity of 98.8% (95% CI 95.7% to 99.9%). EGFR L858R mutation was detected by SP125 antibody with a sensitivity of 94.2% (95% CI 84.1% to 98.8%) and specificity of 99.4% (95% CI 96.5% to 100%). The IHC and PCR cost ratio needed to be 1-to-3 or more in our patients to economically justify before the use of IHC.
CONCLUSIONS
The study confirms an excellent specificity with fairly good sensitivity of IHC and mutation-specific antibodies for common EGFR mutations. It is cost-effective to use IHC method to detect EGFR mutation first when the IHC and PCR cost ratio is 1-to-3 or more in Chinese populations.
Carcinoma, Non-Small-Cell Lung/genetics*
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ErbB Receptors/genetics*
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Humans
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Immunohistochemistry
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Lung Neoplasms/genetics*
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Mutation
6.Quantitative computed tomography-derived abdominal visceral adipose tissue and cardiometabolic risk in a large-scale population
Shengyong DONG ; Xiaojuan ZHA ; Limei RAN ; Yongli LI ; Shuang CHEN ; Jianbo GAO ; Shaolin LI ; Yong LU ; Yuqin ZHANG ; Xiao MA ; YueHua LI ; Xigang XIAO ; Xiangyang GONG ; Zehong YANG ; Wei CHEN ; Yingying YANG ; Bairu CHEN ; Yingru LYU ; Yan WU ; Jing WU ; Kaiping ZHAO ; Xiaoxia FU ; Xia DU ; Haihong FU ; Xiaoguang CHENG ; Qiang ZENG
Chinese Journal of Health Management 2021;15(5):425-431
Objective:To investigate the relationship between abdominal visceral adipose tissue (VAT) and cardiometabolic risk (CMR) through quantitative computed tomography (QCT).Methods:The present study included 76226 participants. Abdominal fat areas were measured using the QCT Pro Model 4 system. Cardiometabolic indices were collected, including systolic and diastolic blood pressures, fasting plasma glucose, total cholesterol, triglyceride, and low-density and high-density lipoprotein cholesterols CMR score was the sum of abnormal blood pressure, fasting glucose, triglyceride, and high-density lipoprotein cholesterol. Restricted cubic spline and ordered logistic regression models were applied.Results:The mean age was 50±13 years and the percentage of men was 58.8%. The level of VAT area was higher in men than in women (191.7±77.1 cm 2 vs 116.4±56.2 cm 2, P<0.0001 for all). After adjustment for age, the cardiometabolic indices except high-density lipoprotein cholesterol increased with increasing VAT area. When VAT area was 300 cm 2, age-adjusted odds ratios and 95% confidence intervals of a CMR score ≥ 1 were 14.61 (13.31, 16.04) for men and 5.46 (4.06, 7.36) for women, and the age-adjusted probability of a CMR score ≥ 3 was 31.7% for men and 31.3% for women. Conclusions:QCT-derived VAT is closely related to CMR. The findings suggest that measurement of visceral fat is recommended for the management of abdominal obesity in subjects who agree to undergo lung cancer screening via low-dose CT without additional radiation exposure.
7.Three-month Follow-up Study of Survivors of Coronavirus Disease 2019after Discharge
Limei LIANG ; Bohan YANG ; Nanchuan JIANG ; Wei FU ; Xinliang HE ; Yaya ZHOU ; Wan-Li MA ; Xiaorong WANG
Journal of Korean Medical Science 2020;35(47):e418-
Background:
Most patients including health care workers (HCWs) survived the coronavirus disease 2019 (COVID-19), however, knowledge about the sequelae of COVID-19 after discharge remains limited.
Methods:
A prospectively observational 3-month follow-up study evaluated symptoms, dynamic changes of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) IgG and IgM, lung function, and high resolution computed tomography (HRCT) of survivors of COVID-19 after discharge at Wuhan Union Hospital, China.
Results:
Seventy-six survivors (55 females) with a mean age of 41.3 ± 13.8 years were enrolled, and 65 (86%) were HCWs. A total of 69 (91%) patients had returned to their original work at 3-months after discharge. Most of the survivors had symptoms including fever, sputum production, fatigue, diarrhea, dyspnea, cough, chest tightness on exertion and palpitations in the three months after discharge. The serum troponin-I levels during the acute illness showed high correlation with the symptom of fatigue after hospital discharge (r = 0.782; P = 0.008) and lymphopenia was correlated with the symptoms of chest tightness and palpitations on exertion of patients after hospital discharge (r = −0.285, P = 0.027; r = −0.363, P = 0.004, respectively). The mean values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, total lung capacity and diffusion capacity were all normal (> 80% predicted) and lung HRCTs returned to normal in most of the patients (82%), however, 42% of survivors had mild pulmonary function abnormalities at 3-months after discharge. SARS-CoV-2 IgG turned negative in 11% (6 of 57 patients), 8% (4 of 52 patients) and 13% (7 of 55 patients), and SARS-CoV-2 IgM turned negative in 72% (41 of 57 patients), 85% (44 of 52 patients) and 87% (48 of 55 patients) at 1-month, 2-months and 3-months after discharge, respectively.
Conclusion
Infection by SARS-CoV-2 caused some mild impairments of survivors within the first three months of their discharge and the duration of SARS-CoV-2 antibody was limited, which indicates the necessity of long-term follow-up of survivors of COVID-19.
8. Invasive breast lobular carcinoma with extracellular mucin: a clinicopathological analysis
Hong LYU ; Limei FU ; Xiaoyu TU ; Hongfen LU ; Ruohong SHUI ; Yufan CHENG ; Xiaoqiu LI ; Wentao YANG
Chinese Journal of Pathology 2019;48(10):779-783
Objective:
To study the clinicopathological features of invasive lobular carcinoma (ILC) of the breast with extracellular mucin and outcomes of patients.
Method:
Clinicopathological features and clinical follow-up (39-123 months and a median follow-up of 55 months) of seven ILC with extracellular mucin were obtained. Hematoxylin-and-eosin (H&E) and immunohistochemistry (IHC) stained sections were reviewed, and fluorescence in situ hybridization (FISH) assay was performed for tumors with HER2 IHC 2+. Patient prognosis was analyzed and literatures related to ILC with extracellular mucin were reviewed.
Results:
All seven patients were female, aged from 43 to 73 years (median age, 55 years). The tumors ranged in size from 1 to 5 cm (median size 2 cm). All seven cases were of histological grade 2. Most areas of the tumors presented with the morphology of classic ILC, and variable amount of extracellular mucin were observed focally. In six cases, part of the tumor cells contained intracellular mucin, and the nucleus were pushed to one side of the cells, creating the impression of signet-ring cells. Two patients had lymph node metastases at diagnosis, and developed liver and bone metastases at 38th and 48th month, respectively, after surgery, and died at 48th and 123th month, respectively. While the other five patients, except one lost to follow-up, had been disease-free during the follow-up period. IHC results showed estrogen receptor (ER) and progesterone receptor (PR) positivity in 7/7 and 6/7 cases, respectively. Tumors of six patients were HER2 IHC 0/1+. The remaining one was HER2 IHC 2+, while FISH assay revealed HER2 gene amplification in that tumor. The proportion of cases with HER2-positivity was 1/7. The proliferation index Ki-67 ranged from less than 5% to 30%, and Ki-67 less than or equal to 10% were in 5/7 cases. According to the 2013 St. Gallen International Expert Consensus on breast cancer, all tumors were of luminal types; of those, two were luminal A and five were luminal B.
Conclusions
ILC with extracellular mucin tends to occur in women over 50 years old. All tumors in the study are grade 2 classic ILC, with signet-ring cells as a common feature. All seven tumors are classified as luminal types, with luminal B as the main molecular subtype.
9.Invasive breast lobular carcinoma with extracellular mucin: a clinicopathological analysis
Hong LYU ; Limei FU ; Xiaoyu TU ; Hongfen LU ; Ruohong SHUI ; Yufan CHENG ; Xiaoqiu LI ; Wentao YANG
Chinese Journal of Pathology 2019;48(10):779-783
Objective To study the clinicopathological features of invasive lobular carcinoma (ILC) of the breast with extracellular mucin and outcomes of patients. Method Clinicopathological features and clinical follow?up (39-123 months and a median follow?up of 55 months) of seven ILC with extracellular mucin were obtained. Hematoxylin?and?eosin (H&E) and immunohistochemistry (IHC) stained sections were reviewed, and fluorescence in situ hybridization (FISH) assay was performed for tumors with HER2 IHC 2+. Patient prognosis was analyzed and literatures related to ILC with extracellular mucin were reviewed. Results All seven patients were female, aged from 43 to 73 years (median age, 55 years). The tumors ranged in size from 1 to 5 cm (median size 2 cm). All seven cases were of histological grade 2. Most areas of the tumors presented with the morphology of classic ILC, and variable amount of extracellular mucin were observed focally. In six cases, part of the tumor cells contained intracellular mucin, and the nucleus were pushed to one side of the cells, creating the impression of signet?ring cells. Two patients had lymph node metastases at diagnosis, and developed liver and bone metastases at 38th and 48th month, respectively, after surgery, and died at 48th and 123th month, respectively. While the other five patients, except one lost to follow?up, had been disease?free during the follow?up period. IHC results showed estrogen receptor (ER) and progesterone receptor (PR) positivity in 7/7 and 6/7 cases, respectively. Tumors of six patients were HER2 IHC 0/1+. The remaining one was HER2 IHC 2+, while FISH assay revealed HER2 gene amplification in that tumor. The proportion of cases with HER2?positivity was 1/7. The proliferation index Ki?67 ranged from less than 5% to 30%, and Ki?67 less than or equal to 10% were in 5/7 cases. According to the 2013 St. Gallen International Expert Consensus on breast cancer, all tumors were of luminal types; of those, two were luminal A and five were luminal B. Conclusions ILC with extracellular mucin tends to occur in women over 50 years old. All tumors in the study are grade 2 classic ILC, with signet?ring cells as a common feature. All seven tumors are classified as luminal types, with luminal B as the main molecular subtype.
10.Prediction and identification of linear B-cell epitopes in the hemagglutinin of H7N9 avian influenza virus in human
Wei TAO ; Meng GAO ; Limin JIANG ; Hui XIE ; Hongxia NI ; Limei GAO ; Yongneng LUO ; Yan HONG ; Zhuojing HE ; Ting FU
Chinese Journal of Clinical Infectious Diseases 2016;9(4):336-341,348
Objective To predict and identify liner B-cell epitopes in the hemagglutinin ( HA) of human-infected avian-origin H7N9 influenza virus and analyze the specificity of H7 subtype.Methods Three serum samples collected at different times from the same patient who was confirmed to be infected with H7N9 influenza virus were provided by Shaoxing People’s Hospital, and one serum sample from healthy person was collected as the control.The extracellular region of HA protein was predicted by TMHMM Sever v.2.0.The potential B-cell epitopes were predicted by DNAStar Lasergene’ s Protean, BcePred and ABCpred tools, and the immunogenicity of the predicted B cell antigen epitopes was assessed by indirect enzyme-linked immunosordent assay ( ELISA ) .H7 subtype specificity was analyzed by comparing HA protein amino acid sequence with H7N9 and H1-H16 subtype influenza virus from Genbank using Clustal X 2.1 software, and Cn3D 4.3.1 software was used to detect the distribution and 3D structure of predicted epitopes on the HA protein of H7N9.Results The potential B-cell epitopes may be located in 172-183, 363-380, 452-472 and 491-506 of extracellular N-terminus of HA protein.ELISA showed that four predicted eptiopes specifically reacted with positive serums from patient.Multi-sequence alignment demonstrated that peptide 172-183 and 363-380 had higher H7 subtype specificity compared with amino acid sequences of other subtypes.Moreover, the predicted linear B-cell epitopes all located on the surface of HA protein according to the 3D structure analysis.Conclusion Four potential B-cell epitopes were identified, in which peptide 172-183 and 363-380 have higher H7 subtype specificity, and may be used in the design of epitope-based vaccines and diagnostics tests.

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