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1.
Biochem Pharmacol ; 226: 116333, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38824966

ABSTRACT

Changes in histone acetylation status are associated with gastric cancer (GC) progression. Pomiferin is a natural flavonoid, however, the specific role of pomiferin in the treatment of GC is still unclear, and its targets are not well clarified. In this work, the prognostic genes related with histone acetylation in GC were screened by univariate Cox analysis. Next, a risk model of was constructed using least absolute shrinkage and selection operator-Cox regression analyses, and multivariate Cox analysis was used for identifying the independent risk factor. Molecular docking was performed using AutoDock Vina to validate the interaction between solute carrier family 9 member A9 (SLC9A9) and pomiferin. In vitro and in vivo models were applied to investigate the tumor-suppressive role of pomiferin against GC. The inhibitory effects of pomiferin on EGFR/PI3K/AKT signaling were valdiated by Western blotting, immunofluorescence staining and qPCR. Here, a prognostic risk model based on histone acetylation regulators was established, and SLC9A9 was identified as a risk factor associated with histone acetylation status in GC. SLC9A9 expression was associated with abnormal immune microenvironment of tumor. Pomiferin had a high binding affinity with SLC9A9, and both pomiferin treatment and depletion of SLC9A9 repressed the malignant phenotypes of GC cells. Mechanistically, pomiferin inactivates EGFR/PI3K/AKT signaling in GC cells. In summary, SLC9A9, as a indicator of abnormal histone acetylation status of GC, functions as an oncogenic factor. Pomiferin binds with SLC9A9 to inactivate EGFR/PI3K/AKT pathway, to block GC progression, suggesting it is a promising drug for the patients with highly malignant GC.


Subject(s)
Histones , Stomach Neoplasms , Stomach Neoplasms/drug therapy , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Humans , Acetylation/drug effects , Histones/metabolism , Animals , Mice , Cell Line, Tumor , Male , Mice, Nude , Female , Molecular Docking Simulation , Mice, Inbred BALB C
2.
Ann Diagn Pathol ; 65: 152149, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37119647

ABSTRACT

INTRODUCTION: Surgery is the only known cure for sporadic pancreatic neuroendocrine tumors (PNETs). Therefore, the prediction of the PNETs biological aggressiveness evaluated on endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has a significant impact on clinical management. The proliferation rate of Ki-67 in PNETs can help to predict the biological aggressiveness of the tumor. In addition, there is a relatively new proliferation marker called phosphorylated histone H3 (PHH3) that can identify and quantify dividing cells in tissue samples, which is a marker highly specific to mitotic figures. Other markers such as BCL-2 also contribute to tumorigenesis and may be involved in the differentiation of neuroendocrine cells. MATERIALS AND METHODS: A retrospective observational study was performed on patients undergoing surveillance for PNETs from January 2010 to May 2021. Data collection included the patients' age, sex, tumor location, tumor size in the surgical specimen, and tumor grade in FNA. The 2019 World Health Organization (WHO) classification guideline was followed to diagnose PNETs, including grade and stage. Immunohistochemical stainings for Ki-67, PHH3 and BCL-2 in PNETs were performed. RESULTS: After excluding cell blocks containing fewer than 100 tumor cells, 44 patients with EUS-FNA and surgical resection specimens were included in this study. There were 19 cases of G1 PNETs, 20 cases of G2 PNETs, and 5 cases of G3 PNETs. The grade assigned based on the Ki-67 index was higher and more sensitive than that based on the mitotic count using H&E slides in some cases of G2 and G3 PNETs. However, there was no significant difference between the mitotic count using PHH3-positive tumor cells and the Ki-67 index to grade PNETs. All grade 1 tumors (19 cases) on surgical resection specimens were correctly graded on FNA (100 % concordance rate). Within the 20 G2 PNETs, 15 cases of grade 2 on surgical resection specimens were graded correctly on FNA based on the Ki-67 index only. Five cases of grade 2 PNETs on surgical resection specimens were graded as grade 1 on FNA when using only the Ki-67 index. Three of five grade 3 tumors on surgical resection specimens were graded as grade 2 on FNA based on the Ki-67 index only. Using only FNA Ki-67 to predict PNET tumor grade, the concordance (accuracy) rate was 81.8 % in total. However, all these eight cases (5 cases of G2 PNETs and 3 cases of G3 PNETs) were graded correctly by using the Ki-67 index plus mitotic rate (using PHH3 IHC stains). Four of 18 (22.2 %) patients with PNETs were positive for BCL-2 stain. In these 4 cases positive for BCL-2 stains, 3 cases were G2 PNETs and one case was G3 PNETs. CONCLUSION: Grade and the proliferative rate in EUS-FNA can be used to predict the tumor grade in surgical resection specimens. However, when using only FNA Ki-67 to predict PNET tumor grade, about 18 % of cases were downgraded by one level. To solve the problem, immunohistochemical staining for BCL-2 and especially PHH3 would be helpful. Our results demonstrated that the mitotic count using PHH3 IHC stains not only improved the accuracy and precision of PNET grading in the surgical resection specimens, but also could reliably be used in routine scoring of mitotic figures of FNA specimens.


Subject(s)
Neuroectodermal Tumors, Primitive , Neuroendocrine Tumors , Pancreatic Neoplasms , Humans , Cell Proliferation , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Histones , Ki-67 Antigen/metabolism , Neoplasm Grading , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/pathology , Pancreatic Neoplasms/pathology , Male , Female
3.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-991031

ABSTRACT

Objective:To explore the evaluation of cytochrome P450 2C19 *2 (CYP2C19 *2) gene polymorphism and Helicobacter pylori (Hp) infection for clopidogrel efficacy in patients with coronary heart disease. Methods:The clinical data of 113 patients with coronary heart disease from February 2016 to March 2020 in Suzhou High-tech Zone People′s Hospital were retrospectively analyzed. The CYP2C19 *2 gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, the Hp infection was detected by 13C urea breath test. The patients were treated with clopidogrel, the effect after 4 weeks was evaluated. The receiver operating characteristic (ROC) curve was used to evaluate the CYP2C19 *2 gene polymorphism and Hp infection for evaluating clopidogrel effect in patients with coronary heart disease. Results:The CYP2C19 *2 genotype in patients with coronary heart disease conformed to Hardy-Weinberg balance ( χ2 = 0.33, P>0.05). Among 113 patients with coronary heart disease, Hp infection was in 27 cases, and Hp non-infection in 86 cases. Among Hp infection patients, CYP2C19 *2 gene GG was in 2 cases, GA in 6 cases, AA in 19 cases; among Hp non-infection patients, CYP2C19 *2 gene GG was in 23 cases, GA in 46 cases, AA in 17 cases, there was statistical difference in CYP2C19 *2 gene polymorphism between the two ( χ2 = 24.35, P<0.01). After clopidogrel treatment, effectiveness was in 79 cases, inefficiency in 34 cases. Among effectiveness patients, YP2C19 *2 gene GG was in 20 cases, GA in 43 cases, AA in 16 cases; among inefficiency patients, CYP2C19 *2 gene GG was in 5 cases, GA in 9 cases, AA in 20 cases, there was statistical difference in CYP2C19 *2 gene polymorphism between the two groups ( χ2 = 16.35, P<0.01). The rate of Hp infection in effectiveness patients was significantly lower than that in inefficiency patients: 12.66% (10/79) vs. 50.00% (17/34), and there was statistical difference ( χ2 = 18.23, P<0.05). ROC curve analysis result showed that the area under the curve of CYP2C19 *2 gene polymorphism combined with Hp infection for evaluating clopidogrel effect in patients with coronary heart disease was larger than CYP2C19 *2 gent GG, GA, AA and Hp infection alone evaluating (0.973 vs. 0.869, 0.679, 0.884 and 0.728) . Conclusions:The CYP2C19 *2 gene polymorphism is associated with Hp infection in patients with coronary heart disease, and the CYP2C19 *2 gene polymorphism combined with Hp infection has the evaluation value for the efficacy of clopidogrel.

4.
Cell Mol Biol (Noisy-le-grand) ; 67(5): 302-308, 2022 Feb 04.
Article in English | MEDLINE | ID: mdl-35818239

ABSTRACT

This study aimed to investigate the levels of cancer antigen 19-9 (CA19-9), neutrophil/lymphocyte ratio (NLR) and systemic immune-inflammatory index (SIRI) in patients with pancreatic cancer with different clinical features and their clinical value. For this purpose, 78 patients with pancreatic cancer treated in our hospital from January 2018 to January 2021 were divided into two groups according to the NLR and SIRI calculated by blood routine and biochemical examination before operation. To observe and analyze the relationship between serum CA19-19 levels, clinical features and NLR and SIRI values in patients with different clinical stages and tumor diameter, and the diagnostic value of CA19-9, NLR and SIRI in pancreatic cancer. The results showed that the level of serum CA19-9 in patients with stage IV pancreatic cancer was significantly higher than that in patients with stage I, II and III, and the level of CA19-9 in patients with stage III was higher than that in patients with stage I and II, and the level of CA19-9 in patients with stage II was higher than that in patients with stage I. The level of CA19-9 in patients with pancreatic cancer with tumor diameter ≥ 5cm was significantly higher than that in patients with tumor diameter < 5cm. The percentage of patients with age ≤ 60 years old in high NLR group (83.78%) was significantly higher than that in low NLR group (63.41%), and the rate of patients with tumor diameter ≥ 5cm in the high SIRI group (54.05%) was significantly higher than that in low NLR group (26.83%). The rate of patients with tumor diameter ≥ 5cm in the high SIRI group (61.92%) was significantly higher than that in the low SIRI group (31.58%). Among the single indexes, the sensitivity of CA19-9 in the diagnosis of pancreatic cancer was the highest (93.10%). The specificity of Siri in the diagnosis of pancreatic cancer was 89.70%. The sensitivity and specificity of combined detection were 89.7% and 70.00%, respectively. In general, the level of serum CA19-9 in patients with pancreatic cancer increases gradually with the increase of clinical stage and tumor diameter. NLR value is related to patient age and tumor diameter, and SIRI value is related to tumor diameter. Combined detection of CA19-9, NLR and SIRI are of higher value in the early diagnosis of pancreatic cancer.


Subject(s)
CA-19-9 Antigen , Pancreatic Neoplasms , Early Detection of Cancer , Humans , Lymphocytes/pathology , Middle Aged , Neutrophils/pathology , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/pathology , Retrospective Studies , Pancreatic Neoplasms
5.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-960492

ABSTRACT

Background Current evidence on whether occupational sulfur dioxide (SO2) exposure affects the risk of hypertension is still limited, and the research results of the effect of environmental SO2 exposure on risk of hypertension remain inconsistent. Objective To analyze the association between self-reported occupational exposure to SO2 and the risk of hypertension, and the potential dose-response relationship between the years of exposure to SO2 and the risk of hypertension. Methods Based on the Jinchang cohort, a nested case-control study design was adopted. A total of 841 newly diagnosed hypertension patients were followed up as the case group, and the control group was selected with 1∶1 individual matching based on non-occupational factors and occupational factors, respectively. The former matching conditions included age ±2 years old, same gender, working age ±2 years, and home address in the same sub-district. The latter was limited to working in the same workshop on the basis of the former conditions. Finally, the former included 717 controls and the latter included 488 controls. A unified questionnaire was used to collect general demographic characteristics, lifestyle habits, history of diabetes, family history of hypertension, and information on occupational exposure to SO2 (self-reported history of occupational exposure to SO2 and years of exposure to SO2). Conditional logistic regression model was used to analyze the association between occupational exposure to SO2 and hypertension, and the dose-response relationship between the years of SO2 exposure and the risk of hypertension. Results In the nested case-control study matching with the non-occupational factors, the OR of hypertension in workers with self-reported occupational exposure to SO2 was 2.39 (95%CI: 1.68-3.39); while when matching with the occupational factors, the OR of hypertension in workers with self-reported occupational exposure to SO2 was 1.48 (95%CI: 1.04-2.12). The results of the dose-response relationship showed that as the SO2 exposure years increased from 1-9 years, 10-19 years, 20-29 years, and 30 years and above, in the nested case-control study matching with non-occupational factors, the ORs of hypertension were 1.85 (95%CI: 0.68-5.08), 1.46 (95%CI: 0.58-3.67), 1.64 (95%CI: 1.00-2.67), and 4.95 (95%CI: 2.63-9.31), respectively; in the nested case-control study matching with occupational factors, the ORs of hypertension were 0.98 (95%CI: 0.40-2.41), 1.84 (95%CI: 0.72-4.70), 1.37 (95%CI: 0.82-2.29), and 2.44 (95%CI: 1.37-4.35), respectively. The two dose-response relationships were positive by χ2 trend test (Ptrend<0.05). Conclusion Self-reported occupational exposure to SO2 is associated with the risk of hypertension in the study population, and the hypertension risk increases with the increase of SO2 exposure years.

6.
Protein & Cell ; (12): 239-257, 2022.
Article in English | WPRIM (Western Pacific) | ID: wpr-929163

ABSTRACT

Studies on diabetes have long been hampered by a lack of authentic disease models that, ideally, should be unlimited and able to recapitulate the abnormalities involved in the development, structure, and function of human pancreatic islets under pathological conditions. Stem cell-based islet organoids faithfully recapitulate islet development in vitro and provide large amounts of three-dimensional functional islet biomimetic materials with a morphological structure and cellular composition similar to those of native islets. Thus, islet organoids hold great promise for modeling islet development and function, deciphering the mechanisms underlying the onset of diabetes, providing an in vitro human organ model for infection of viruses such as SARS-CoV-2, and contributing to drug screening and autologous islet transplantation. However, the currently established islet organoids are generally immature compared with native islets, and further efforts should be made to improve the heterogeneity and functionality of islet organoids, making it an authentic and informative disease model for diabetes. Here, we review the advances and challenges in the generation of islet organoids, focusing on human pluripotent stem cell-derived islet organoids, and the potential applications of islet organoids as disease models and regenerative therapies for diabetes.


Subject(s)
Humans , COVID-19 , Diabetes Mellitus/therapy , Islets of Langerhans , Organoids , SARS-CoV-2
7.
Cancer Research and Clinic ; (6): 209-214, 2022.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-934659

ABSTRACT

Objective:To investigate the correlation between mammographic density (MD) and breast cancer-related reproductive risk factors in healthy women.Methods:A retrospective analysis was performed on 2 027 women who participated in breast health examinations in Shanxi Provincial People's Hospital from July 2019 to June 2021, and the mammography classifications were Breast Imaging Reporting and Data System (BI-RADS) categories 1-2. Quantra software was used to assess volume of fibroglandular (VFG) and volumetric breast density (VBD) in premenopausal and postmenopausal women, and the volume of non-fibroglandular (N-VFG) was calculated. Multiple linear regression analysis was used to analyze the correlation between MD and breast cancer-related reproductive risk factors.Results:Among the 2 027 healthy women, 1 149 (56.7%) were premenopausal women, and 96.3% (1 107 women) were reproductive women; 878 (43.3%) were postmenopausal women, and 97.6% (857 women) were reproductive women. Among 1 149 healthy premenopausal women, compared with nulliparous women, women who had given birth had lower VBD ( P = 0.036); among women who had given birth, with the increase of the number of births, VBD showed a downward trend, and N-VFG showed a trend of decline. Compared with women who gave birth once, VBD decreased by 1.12% ( P < 0.001), N-VFG increased by 27.01 cm 3 ( P = 0.043) in women who had given birth twice, and VBD decreased by 2.02% ( P < 0.001), N-VFG increased by 90.10 cm 3 ( P < 0.001) in women who had given birth ≥3 times. Among 878 healthy postmenopausal women, compared with non-breastfeeding women, the VFG and VBD showed a downward trend with the prolongation of breastfeeding time. When the breastfeeding time was ≥24 months, VFG decreased by 17.25 cm 3 ( P = 0.004) and VBD decreased by 3.23% ( P < 0.001). Among women who had given birth, with the increase in the number of births, VFG and VBD showed a downward trend, and N-VFG showed an upward trend. Compared with women who had given birth once, the VFG of women who had given birth twice decreased by 11.88 cm 3 ( P = 0.001), VBD decreased by 2.49% ( P < 0.001), the VFG of women who had given birth ≥3 times decreased by 21.26 cm 3 ( P < 0.001), VBD decreased by 4.19% ( P < 0.001), and N-VFG increased by 52.88 cm 3 ( P = 0.019). With the increase of the first birth age, VFG and VBD of women showed an increasing trend. Compared with women with the first birth age of ≤ 24 years old, VFG of women with the first birth age of 25-29 years old increased by 8.47 cm 3 ( P = 0.010), VBD increased by 1.16% ( P = 0.013), and the VFG of women with the first birth age of ≥30 years old increased by 16.25 cm 3 ( P = 0.018). Conclusions:There is a correlation between MD and breast cancer-related reproductive risk factors in healthy women with different menstrual status.

8.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-934025

ABSTRACT

Objective:To investigate the changes in epidemiological characteristics of common respiratory pathogens in children in Beijing during COVID-19 epidemic.Methods:A total of 9 728 serum samples were collected from cases of acute respiratory infections in Beijing Children′s Hospital from January 2020 to December 2020. Indirect immunofluorescence antibody test was performed to detect IgM antibodies against eight common respiratory pathogens and the test results were statistically analyzed. The eight common respiratory pathogens were influenza virus A (FluA), influenza virus B (FluB), respiratory syncytial virus (RSV), adenovirus (ADV), parainfluenza virus (PIV), Mycoplasma pneumoniae ( Mp), Chlamydia pneumoniae ( Cp) and Legionella pneumophila ( Lp). Results:The detection rate of respiratory pathogens in 9 728 cases was 41.71% (4 058/9 728) and respiratory viruses (FluA, FluB, RSV, ADV and PIV) accounted for 46.18%(2 343/5 074)of all detected pathogens. Mp, FluB and FluA accounted for 84.73%(4 299/5 074)of all detected pathogens, and the detection rates were 24.27% (2 361/9 728), 11.49% (1 118/9 728) and 8.43% (820/9 728), respectively. There were 846 cases positive for two kinds of pathogens, and the most common co-infection was Mp and FluB. The detection rates in male and female were 37.56% (2 089/5 562) and 47.26% (1 969/4 166), respectively. There were significant differences in the total detection rate and the positive rates of PIV and Mp between different sexes ( P<0.05). The detection rate in school-age children (6-12 years old) was the highest (52.26%, 1 535/2 937). The detection rates of respiratory pathogens in different months ranged from 30.12% (203/674) to 49.81% (268/538) with higher rates in autumn and winter [42.45% (1 304/3 072) and 43.29% (1 618/3 738)]. The detection rates of FluA and FluB were higher in summer [11.46% (195/1 701)] and winter [14.63% (547/3738)], respectively. Most of RSV infection occurred in summer [1.35% (23/1 701)], and Mp could be detected all year round, especially in winter and spring [27.21% (1 017/3 738) and 25.64% (312/1 217)]. The detection rate of respiratory pathogens in outpatient group was higher than that in inpatient group [46.48% (1 583/3 406) vs 39.15% (2 475/6 322)]. The detection rate in severe cases was 26.10% (71/272). The detection rates of total pathogens, FluB and Mp were higher in outpatients than in inpatients and the differences were statistically significant ( P<0.05). The detection rates of FluA, PIV and ADV were higher in inpatients than in outpatients and the differences were statistically significant ( P<0.05). The detection rates of total pathogens, FluB and Mp in mild cases were significantly higher than those in severe cases and the differences were statistically significant ( P<0.05). The detection rate of RSV in severe cases was significantly higher than that in mild cases and the difference was statistically significant ( P<0.05). Conclusions:The protective measures taken during the period of regular prevention and control of COVID-19 epidemic could better prevent the spread of respiratory viruses, having a certain impact on the population susceptible to respiratory pathogens and typical seasonal patterns, but had little effect on the prevention and control of Mp. New protective measures needed to be studied to prevent Mp infection in children during epidemical season.

9.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-958575

ABSTRACT

Objective:To investigate the clinical significance and the diagnostic value of detecting kidney injury biomarkers in urine and serum of children with Henoch-Sch?nlein purpura nephritis (HSPN).Methods:A total of 216 children with untreated HSPN, who were admitted in Beijing Children′s Hospital of Capital Medical University from January 2018 to December 2019, were recruited in this retrospective study. Two hundred and sixteen healthy children were selected as the healthy control group. We determined the levels of six biomarkers of kidney injury, including transferrin (TRF), immunoglobulin (IgG), microalbumin (mAlb), alpha-1 microglobulin (α1-MG), N-acetyl-β-D-glucosaminidase (NAG) in urine and cystatin C (CysC) in serum. The data from the two groups were analyzed, the diagnostic value of each biomarker was evaluated and a logistic regression model for the diagnosis of HSPN was established. In addition, 60 children with HSPN, who were admitted to our hospital from November 2021 to February 2022 and 60 healthy children, who underwent healthy check up in the same period were included to validate the diagnostic performance of the established logistic model. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of each biomarker.Results:The urine levels of TRF, IgG, mAlb, α1-MG and NAG and the serum level of CysC were significantly higher in the HSPN group than those in healthy control group (all P<0.05). The area under the ROC curve (AUC) of TRF, IgG, mAlb, α1-MG, NAG and the serum levels of CysC was 0.749, 0.719, 0.810, 0.648, 0.828 and 0.790 (all P<0.05). Logistics regression analysis showed that IgG, mAlb and TRF were the three diagnostic determinants of HSPN ( OR=1.083, 1.105, 1.704,all P<0.001), and the AUC was 0.916 of the established logistic model based on these three biomarkers. The sensitivity was 87.4% and the specificity reached 96.2%. The logistic model was validated by independent cohorts, and the AUC was 0.973, the sensitivity was 95.0% and the specificity was 98.3%. Conclusions:The levels of urine TRF, IgG, mAlb, α1-MG, NAG and serum CysC were higher in children with HSPN. The established logistic regression model based on three biomarkers including IgG, mAlb and TRF in this study has satisfactory clinical value in diagnosing HSPN in children.

10.
Preprint in English | bioRxiv | ID: ppbiorxiv-452910

ABSTRACT

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is currently a global pandemic. Extensive investigations have been performed to study the clinical and cellular effects of SARS-CoV-2 infection. Mass spectrometry-based proteomics studies have revealed the cellular changes due to the infection and identified a plethora of interactors for all SARS-CoV-2 components, except for the longest non-structural protein 3 (NSP3). Here, we expressed the full-length NSP3 proteins of SARS-CoV and SARS-CoV-2 to investigate their unique and shared functions using multi-omics methods. We conducted interactome, phosphoproteome, ubiquitylome, transcriptome, and proteome analyses of NSP3-expressing cells. We found that NSP3 plays essential roles in cellular functions such as RNA metabolism and immune response such as NF-{kappa}B signal transduction. Interestingly, we showed that SARS-CoV-2 NSP3 has both endoplasmic reticulum and mitochondrial localizations. In addition, SARS-CoV-2 NSP3 is more closely related to mitochondrial ribosomal proteins, whereas SARS-CoV NSP3 is related to the cytosolic ribosomal proteins. In summary, our multi-omics studies of NSP3 enhance our understanding of the functions of NSP3 and offer valuable insights for the development of anti-SARS strategies.

11.
Preprint in English | bioRxiv | ID: ppbiorxiv-434733

ABSTRACT

The spike (S) protein of SARS-CoV-2 has been observed in three distinct pre-fusion conformations: locked, closed and open. Of these, the function of the locked conformation remains poorly understood. Here we engineered a SARS-CoV-2 S protein construct "S-R/x3" to arrest SARS-CoV-2 spikes in the locked conformation by a disulfide bond. Using this construct we determined high-resolution structures confirming that the x3 disulfide bond has the ability to stabilize the otherwise transient locked conformations. Structural analyses reveal that wild-type SARS-CoV-2 spike can adopt two distinct locked-1 and locked-2 conformations. For the D614G spike, based on which all variants of concern were evolved, only the locked-2 conformation was observed. Analysis of the structures suggests that rigidified domain D in the locked conformations interacts with the hinge to domain C and thereby restrains RBD movement. Structural change in domain D correlates with spike conformational change. We propose that the locked-1 and locked-2 conformations of S are present in the acidic high-lipid cellular compartments during virus assembly and egress. In this model, release of the virion into the neutral pH extracellular space would favour transition to the closed or open conformations. The dynamics of this transition can be altered by mutations that modulate domain D structure, as is the case for the D614G mutation, leading to changes in viral fitness. The S-R/x3 construct provides a tool for the further structural and functional characterization of the locked conformations of S, as well as how sequence changes might alter S assembly and regulation of receptor binding domain dynamics.

12.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-910169

ABSTRACT

Objective:To investigate the clinical characteristics and perinatal outcomes of pregnancy with placental cystic lesions.Methods:A retrospective study was carried out on 48 pregnant women diagnosed as pregnancy complicated with placental cystic lesions from January 2000 to January 2020 at the Women′s Hospital, Zhejiang University School of Medicine. The clinical features, pathological diagnosis and perinatal outcome were analyzed.Results:The age of 48 cases was (30±5) years, and the diagnostic gestational week of ultrasound was (24±8) weeks. Twenty-five cases in which showed a cystic mass at the fetal surface were diagnosed as placental cyst. The live birth rate was 100% (25/25) and the premature birth rate was 20% (5/25). Twenty-three cases showed “honeycomb like” cystic echo. Cystic lesions of 10 cases were located in the uterine cavity connected with the margin of the normal placenta, and finally diagnosed as hydatidiform mole and coexisting fetus (HMCF). Six cases of HMCF terminated pregnancy, and the live birth rate was 4/10, the premature delivery rate was 2/4. Cystic lesions of 13 cases were located in the placenta substance, and finally diagnosed as 4 cases of placental mesenchymal dysplasia (PMD) and 9 cases of focal chorionic edema; the live birth rate was 6/13 and the premature delivery rate was 4/6. The median hCG was lower in focal chorionic edema group [80 kU/L (60-110 kU/L)] than in the groups of HMCF [240 kU/L (180-430 kU/L)] and PMD [360 kU/L (210-700 kU/L)], and the differences were statistically significant (all P<0.01). Conclusions:For pregnancy complicated with placental cystic lesions, prenatal ultrasound should be performed to evaluate the shape, location and blood flow of the lesions. Maternal serological examination and invasive prenatal diagnosis are helpful for prenatal diagnosis and treatment. Due to the difference of perinatal outcomes, maternal and fetal complications, individualized pregnancy management should be carried out.

13.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-882519

ABSTRACT

Long non-coding RNA (lncRNA) is a type of RNA molecule whose transcript is longer than 200 nucleotides and cannot encode protein. Studies in recent years have shown that lncRNA plays an important role in the physiological and pathological processes of the body. It participates in the occurrence, development and metastasis of prostate cancer. Further study on the role and mechanism of lncRNA in prostate cancer is expected to provide new ideas for the diagnosis and treatment of prostate cancer.

14.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-988353

ABSTRACT

Pancreatic ductal adenocarcinoma is one of the most common malignant tumors. Its early diagnosis and treatment are very difficult, and the mortality and recurrence rate are high. Chronic pancreatitis is an important risk factor for pancreatic cancer and has great potential to develop into pancreatic cancer. Therefore, it is necessary to study the mechanism of pancreatitis-cancer transformation for early diagnosis and treatment of pancreatic cancer. In recent years, more and more studies have shown that epigenetic modification plays an important role in pancreatitis-cancer transformation, and can provide an effective target for the diagnosis and treatment of pancreatic cancer. This article summarizes the role and mechanism of epigenetics in pancreatitis-cancer transformation based on the current research progress.

15.
Chinese Journal of Pathology ; (12): 112-115, 2019.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-810448

ABSTRACT

Objective@#To elucidate the clinicopathologic characteristics of atypical epithelioid trophoblastic lesions with cyst and fistula formation after cesarean section.@*Methods@#The clinical and pathological data of 4 cases of post-cesarean atypical epithelioid trophoblastic lesions with cyst and fistula formation diagnosed at Women′s Hospital, School of Medicine, Zhejiang University during April 2007 to June 2018 were evaluated by hematoxylin and eosin stain and EnVision two-step immunohistochemical staining technique.@*Results@#The age of the 4 patients ranged from 32 to 41 years, with a mean age of 36.5 years. Three patients recieved cystectomy and one underwent subtotal hysterectomy. Histologically, the lesions were well circumscribed and consisted of uniform cells of medium size, irregularly enlarged with hyperchromatic nuclei and 1 to 2 inconspicuous nucleoli embedded in abundant hyalinized matrix with fibrinoid material in the center. The cells exhibited immunohistochemical feature of chorionic-type intermediate trophoblastic cells (CK18+, p63+ and CD146-). All patients were alive without recurrence during follow-up of 1 to 40 months (mean=22 months).@*Conclusion@#Atypical epithelioid trophoblastic lesion with cyst and fistula formation after cesarean section has unique histological features, and its biological behavior and prognosis are still unclear, which need further exploration.

16.
Chinese Journal of Trauma ; (12): 913-917, 2019.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-796377

ABSTRACT

Objective@#To investigate the effect of construction of trauma care center on the treatment of patients with severe multiple trauma.@*Methods@#A retrospective case control study was conducted to analyze the clinical data of 412 patients with severe multiple trauma admitted to the First Affiliated Hospital of Soochow University from December 2015 to November 2017. There were 250 males and 162 females, aged 19-80 years [(45.8±15.9)years]. The injury severity score (ISS) ranged from 18 to 57 points [(28.2±9.3)points]. The observation group included 211 patients who were treated after the establishment of the provincial trauma treatment center in Jiangsu Province, and the control group included 201 patients who were treated before the establishment of the provincial trauma treatment center. The durations from arrival to the start of rescue, from consultation to completion of CT examination, from applying for blood transfusion to the execution of blood transfusion by nurses, the time of stay at the resuscitation room and the mortality rate were compared between the two groups.@*Results@#The observation group presented better results in the durations from arrival to the start of rescue [(2.5±1.7)minutes vs. (5.4±2.6)minutes], from the start of the rescue to completion of CT scan [(36.2±11.6)minutes vs. (53.2±12.9)minutes], the transfusion time [(28.7±11.3)minutes vs. (46.5±14.1)minutes], and the time of stay at resuscitation room [(3.0±2.0)hours vs. (5.0±2.8)hours] (P<0.05 or 0.01). The mortality rate in the observation group was 3.8% (8/211), which was significantly lower than 8.5% (17/201) in control group (P<0.05).@*Conclusion@#The construction of trauma treatment center can effectively shorten the treatment time of patients with severe multiple trauma, reduce the mortality rate and improve the efficacy, which is worthy of promotion.

17.
Chinese Journal of Trauma ; (12): 913-917, 2019.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-791249

ABSTRACT

Objective To investigate the effect of construction of trauma care center on the treatment of patients with severe multiple trauma.Methods A retrospective case control study was conducted to analyze the clinical data of 412 patients with severe multiple trauma admitted to the First Affiliated Hospital of Soochow University from December 2015 to November 2017.There were 250 males and 162 females,aged 19-80 years [(45.8 ±15.9)years].The injury severity score (ISS) ranged from 18 to 57 points [(28.2 ±9.3)points].The observation group included 211 patients who were treated after the establishment of the provincial trauma treatment center in Jiangsu Province,and the control group included 201 patients who were treated before the establishment of the provincial trauma treatment center.The durations from arrival to the start of rescue,from consultation to completion of CT examination,from applying for blood transfusion to the execution of blood transfusion by nurses,the time of stay at the resuscitation room and the mortality rate were compared between the two groups.Results The observation group presented better results in the durations from arrival to the start of rescue [(2.5 ±1.7) minutes vs.(5.4 ± 2.6) minutes],from the start of the rescue to completion of CT scan [(36.2 ±11.6) minutes vs.(53.2 ± 12.9) minutes],the transfusion time [(28.7 ± 11.3) minutes vs.(46.5 ±14.1) minutes],and the time of stay at resuscitation room [(3.0 ± 2.0) hours vs.(5.0 ± 2.8) hours](P<0.05 or 0.01).The mortality rate in the observation group was 3.8% (8/211),which was significantly lower than 8.5% (17/201) in control group (P < 0.05).Conclusion The construction of trauma treatment center can effectively shorten the treatment time of patients with severe multiple trauma,reduce the mortality rate and improve the efficacy,which is worthy of promotion.

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Article in Chinese | WPRIM (Western Pacific) | ID: wpr-753933

ABSTRACT

Objective To explore the relationship between cognitive function and oxidative stress biochemical markers in patients with bipolar disorder. Methods One hundred forty-six patients who met the DSM-Ⅳ bipolar disorder diagnostic criteria including 83 patients with stable phase,42 patients with manic episodes and 21 patients with depression and 115 normal controls were recruited. Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess cognitive function. Biochemical indicators were measured including superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT), malonaldehyde (MDA), total antioxidant capacity (T-AOC) and nitric oxide (NO). Results The immediate memory, speech function, attention, time-delay memory, and total score of patients in biphasic stable phase, manic phase, and depression were lower than those in the control group (P<0.01). The visual breadth scores of patients in manic and depression were lower than those in the control group (P<0.01), and the attention scores and total scores were lower than those in the stable group (P<0.01). The delayed memory score of patients with depression was lower than that of stable group (P=0.04). The MDA level of patients with manic episode and depression was higher than that of stable group (P<0.01); the level of NO in manic, depression and control group was higher than that in stable group, and CAT level was low in the stable phase group (P<0.05). In the stable phase group, the visual breadth (r=-0.50, P=0.04), attention (r=-0.67, P<0.01), delayed memory (r=-0.61, P=0.01) were correlated with GSH-PX respectively; time-delay memory was negatively correlated with T-AOC (r=-0.54, P=0.03). The speech function of the biphasic mania phase group was negatively correlated with SOD (r=-0.46, P=0.01). The immediate memory of the biphasic depression group was positively correlated with NO (r=0.61, P=0.02); delayed memory was positively correlated with CAT (r=0.67, P=0.01); speech function (r=-0.76, P<0.01) and cognitive total score (r=-0.59, P=0.03) were negatively correlated with GSH-PX. Conclusion Patients with bipolar disorder have varying degrees of cognitive decline and oxidative stress changes, and some antioxidant enzyme systems are associated with cognitive function.

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Article in Chinese | WPRIM (Western Pacific) | ID: wpr-753918

ABSTRACT

Objective This study aims to investigate the sex difference in the hippocampus and parahippocampus in patients with bipolar disorder. Methods We acquired T1-weighted structural MRI from 133 bipolar type I patients (60 males) and 144 normal controls (81 males). The General Linear Model was used to examine the relationship between sex and brain volumes of the hippocampus and parahippocampus, with age and intracranial volume as covariates. Results Patients showed significantly smaller volumes of the bilateral hippocampus and parahippocampus (P<0.01). There were sex-by-diagnosis interactions in the left parahippocampus gyrus (F=6.534, P=0.044). Male patients had significant smaller volumes of the left parahippocampus gyrus compared to the male normal controls (P<0.001) whereas the volumes were not significantly different between female patients and female normal controls (P>0.05). Conclusion The results suggest sex difference in the left parahippocampus gyrus volume in patients with bipolar type I disorder, which deserves further investigation in the future bipolar imaging researches.

20.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-855976

ABSTRACT

Objective: To investigate the impact of serum brain-derived neurotrophic factor (BDNF) levels on depression of hypertensive cerebral hemorrhage(HICH) patients with conservative treatment. Methods: From April 2014 to December 2017, a total of 63 patients with HICH hospitalized in the Department of Neurosurgery, Tangshan Gongren Hospital were enrolled. There were 38 males and 25 females patients. All had intracranial hematoma volume within 30 ml and received conservative treatment. Serum BDNF levels were detected using enzyme linked immunosorbent assay. The paralysis grade was assessed using National Institutes of Health Stroke Scale (NIHSS) on admission and the 21 st day after admission. The Zung Depression Self-rating Scale(SDS) was used to evaluate depression 21 days after admission. Patients with SDS score ≥53 were divided into the depression group and with SDS score < 53 were divided into the non-depression group. The differences of serum BDNF levels between the two groups were compared. Risk factors for depression of HICH patients with conservative treatment were analyzed by binary Logistic regression analysis. Results: The SDS score of the depression group (54. 7 ± 1.5) on the 21st day after admission was significantly higher than that of the non-depression group (44. 6 ± 6. 5, 1 =7. 020, P <0. 01). The serum BDNF levels of the depression group was lower than that of the non-depression group(7. 0 ± 1. 4 p, g/L vs. 8. 6 ± 1. 8 p, g/L, t = - 3. 433, P = 0. 001). The paralysis grade of the depression group was higher than that of the non-depression group on the 21st day after admission (5. 4 ± 1. 5 vs. 3. 8 ± 1. 1, t =4. 951, P <0. 01). In the depression group, the serum BDNF level was negatively correlated with SDS score(r = -0. 535, P =0. 013).blood loss(r= - 0. 578, P = 0. 006) and paralysis grade(r= -0. 715, P<0. 01) on the 21st day after admission. In binary Logistic regression analysis, serum BDNF level was a protective factor for depression in HICH patients undergoing conservative treatment(OR, 0. 990, 95% CI 0. 983-0. 997, P = 0. 008). Conclusion: The lower the serum BDNF levels of HICH patients with conservative treatment, the more prone to depression.

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