1.Mutational Signatures Analysis of Micropapillary Components and Exploration of ZNF469 Gene in Early-stage Lung Adenocarcinoma with Ground-glass Opacities.
Youtao XU ; Qinhong SUN ; Siwei WANG ; Hongyu ZHU ; Guozhang DONG ; Fanchen MENG ; Zhijun XIA ; Jing YOU ; Xiangru KONG ; Jintao WU ; Peng CHEN ; Fangwei YUAN ; Xinyu YU ; Jinfu JI ; Zhitong LI ; Pengcheng ZHU ; Yuxiang SUN ; Tongyan LIU ; Rong YIN ; Lin XU
Chinese Journal of Lung Cancer 2024;26(12):889-900
BACKGROUND:
In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration.
METHODS:
A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases.
RESULTS:
MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05).
CONCLUSIONS
The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans
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Lung Neoplasms/genetics*
;
Adenocarcinoma of Lung/genetics*
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China
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Prognosis
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Transcription Factors
2.Primary malignant melanoma of penis: a case report
Zhitong CHEN ; Long HUANG ; Xiaobin CHEN ; Xiaofeng ZHOU ; Shuang CHEN ; Wenlong CHENG ; Guojun CHEN
Chinese Journal of Urology 2024;45(8):633-634
This article reports a case data of primary malignant melanoma of the penis admitted to the Affiliated Hospital of Qinghai University. A 56-year-old patient was admitted to the hospital 1 month after the discovery of a penile mass. Physical examination: An irregular cauliflower-like mass about 1.5 cm×2.0 cm in size was seen below the external urethral orifice, covered with yellow necrotic tissue, and tenderness was positive. Several nodes were palpable in the left and right groin areas, tenderness positive. Laboratory examination showed no abnormality. The CT examination of head, chest, abdomen and pelvis showed no obvious abnormality. The biopsy of the penile mass showed malignant melanoma of the penis. The pathological results of biopsy of the right inguinal lymph node considered local inflammation. Combined with the patient's medical history, physical examination, imaging examination and lymph node biopsy results, a diagnosis of primary penile malignant melanoma was made. Partial penile resection was performed, and the postoperative pathological diagnosis was malignant melanin invasion of the epidermis with ulceration. There was no local recurrence and metastasis during the 9-month follow-up.
3.Preparation and Performance Investigation of Aprepitant Ternary Supersaturated Solid Dispersion System
Jing YANG ; Ting CHEN ; Bingxi WANG
Chinese Journal of Modern Applied Pharmacy 2024;41(10):1365-1371
OBJECTIVE
To improve the solubility of the insoluble drug aprepitant, solve the problem of solubilization in acid and crystallization and precipitation in alkali of aprepitant, select polymer carriers with different functions, prepare ternary solid dispersions, and investigate their performance.
METHODS
Binary solid dispersions were prepared by solvent-melt method, and the solubility and dissolution rate were used as indicators to screen the solubilization-enhancing carrier materials. The crystallization inhibition performance of each polymer in different concentrations of drug solutions was investigated by the medium transfer method, and the best precipitation inhibitor was screened. The ternary solid dispersions were prepared by hot melt extrusion technique, and the ternary solid dispersion prescriptions were preferably selected with the indexes of solubility and crystal inhibition time. The presence of the drug in the carrier was confirmed by X-ray diffraction analysis, and the dynamic solubility and physical stability of the ternary solid dispersion in simulated intestinal fluid under accelerated conditions were investigated.
RESULTS
The binary solid dispersion prepared by hydrophilic polymer PVP K30 showed fast dissolution and good solubilization, the enterosoluble polymer HPMCAS showed superior crystal inhibition and prolonged the supersaturation point of aprepitant, and the ternary solid dispersion with a mass ratio of 1∶1∶3(APR∶PVP K30∶HPMCAS) was rapidly and completely released in acid(95% dissolution at 120 min). The ternary solid dispersions were completely released and maintained the solution in a highly supersaturated stable state at 6 h when the pH of the medium was shifted to 6.8, which significantly increased the dissolution degree and dissolution rate relative to the APR, and the drug existed in the carrier matrix in an amorphous form, while being able to maintain the amorphous state for at least three months under accelerated conditions.
CONCLUSION
Based on the physicochemical properties of different polymers, the ternary solid dispersion prepared in this work not only significantly improves the solubility of aprepitant by coordinating the dissolution rate and crystallization inhibition effect, but also solves the problem of aprepitant dissolution in stomach and precipitation in intestine, with good dissolution characteristics.
4.Clinical effect of multi-modality image fusion combined with intraoperative fluorescein sodium in the treatment of brain metastases from lung cancer
Zhong WANG ; Xiaojun ZHANG ; Ruijian ZHANG ; Zhitong HAN ; Weiran YANG ; Wenbo YANG ; Yunzhao CHEN ; Dong XING ; Junqing WANG ; Yuhui SONG
Clinical Medicine of China 2024;40(6):447-455
Objective:To explore the application and clinical efficacy of functional neural navigation multimodal image fusion technology combined with intraoperative fluorescein sodium in the surgery of lung cancer brain metastases.Methods:Forty patients with lung cancer and brain metastasis admitted to the Department of Neurosurgery of Inner Mongolia Autonomous Region People's Hospital from January 2020 to January 2024 were collected as the observation group. Another 40 patients with lung cancer brain metastases who underwent microscopic resection at Inner Mongolia Autonomous Region People's Hospital from January 2016 to December 2019 were selected as the control group. All patients received head CT examination, head MRI examination, MRI enhanced sequence and MRA, MRV and DWI sequence scanning before operation. Functional neural navigation system was used to perform preoperative multi-modal image fusion to realize three-dimensional display of tumor lesions, and display the position relationship between tumor and functional areas, conduction bundles and large blood vessels, so as to make preoperative navigation plan. After conducting a fluorescein sodium allergy test on the patient before surgery, a small dose of fluorescein sodium (2 mg/kg) was intravenously injected during the operation. During the operation, neuro navigation was combined with fluorescein sodium to perform tumor resection by displaying the boundary between tumor tissue and normal brain tissue under a Pentero 900 Zeiss microscope 560 fluorescence mode. Both groups collected tumor tissue samples for pathological classification and immunohistochemical analysis, comparing and analyzing differences in tumor resection degree, postoperative occurrence of new neurological dysfunction, postoperative muscle strength improvement, changes in KPS scores before and after surgery, and the occurrence of complications. The metric data that conforms to normal distribution is represented by xˉ± s, and the comparison of means between two groups is conducted using independent sample t-test. Calculate the percentage based on the count data, and compare the inter group rates using the χ2 test. P<0.05 indicates statistical significance of the difference. Results:Compared with the control group, the total tumor resection rate of observation group (75.0% (30/40) ) and KPS score of 3 months after surgery (82.5% (33/40)) were better than those of the control group (52.5% (21/40) and 60% (24/40)), and the differences were statistically significant ( χ2 value was 4.94 and 4.38, P values were 0.026 and 0.036). The rate of postoperative new neurological dysfunction in the observation group (22.5% (9/40)) was lower than that in the control group (45.0% (18/40)), and the difference between the two groups was statistically significant ( χ2=4.53, P=0.033). The length of hospital stay ((21.48±3.23) days), operation time ((216.65±56.76) points) and complication rate (37.5% (15/40)) in observation group were lower than those in control group ((22.43±2.34) days, (225.62±37.68) points, 45.0% (18/40)). However, the difference was not statistically significant ( t/ χ2 values were 1.51, 0.83, and 0.46, respectively; P values were 0.136, 0.408, and 0.496, respectively). The 12-month survival rate of observation group (67.5%(27/45) respectively was significantly higher than that of control group (40.0%(16/40) respectively, and the difference was statistically significant ( χ2=6.08, P=0.014). Conclusion:Functional neural navigation multimodal image fusion technology combined with intraoperative fluorescein sodium can accurately locate the tumor and determine the boundary relationship between the tumor and normal brain tissue during lung cancer brain metastasis surgery, improve tumor resection rate, enhance patient quality of life, and ultimately improve patient prognosis without increasing the risk of related complications.
5.Transient Peripheral Carotid Inflammation Syndrome Diagnosed by Contrast-enhanced Ultrasound: A Case Report
Chunlei PAN ; Ying WANG ; Yahong WANG ; Li ZHANG ; Zhitong GE ; Yu CHEN ; Sheng CAI ; Hongyan WANG ; Xiao YANG ; Jianchu LI
Medical Journal of Peking Union Medical College Hospital 2024;16(3):785-789
Transient perivascular inflammation of the carotid artery (TIPIC) syndrome is a relatively rare disease, and ultrasound is the first screening method for initial diagnosis of the disease. Contrast-enhanced ultrasound (CEUS) has unique advantages in the follow-up of patients with TIPIC syndrome. This paper reports a patient with TIPIC syndrome who was treated with acute left neck pain. The inflammation was significantly relieved and subsided after treatment with non-steroidal anti-inflammatory drugs. The ultrasound changes of carotid artery lesions in this patient during follow-up were analyzed, and the application value of CEUS in the follow-up diagnosis of this disease was summarized, in the hope of providing clinical reference.
6.Screening and identification of a polyurethane-degrading bacterium G-11 and its plastic degradation characteristics.
Zhitong JIANG ; Xue CHEN ; Jinhui LEI ; Huizhen XUE ; Bo ZHANG ; Xiaofan XU ; Huijing GENG ; Zhoukun LI ; Xin YAN ; Weiliang DONG ; Hui CAO ; Zhongli CUI
Chinese Journal of Biotechnology 2023;39(5):1963-1975
Polyurethane (PUR) plastics is widely used because of its unique physical and chemical properties. However, unreasonable disposal of the vast amount of used PUR plastics has caused serious environmental pollution. The efficient degradation and utilization of used PUR plastics by means of microorganisms has become one of the current research hotspots, and efficient PUR degrading microbes are the key to the biological treatment of PUR plastics. In this study, an Impranil DLN-degrading bacteria G-11 was isolated from used PUR plastic samples collected from landfill, and its PUR-degrading characteristics were studied. Strain G-11 was identified as Amycolatopsis sp. through 16S rRNA gene sequence alignment. PUR degradation experiment showed that the weight loss rate of the commercial PUR plastics upon treatment of strain G-11 was 4.67%. Scanning electron microscope (SEM) showed that the surface structure of G-11-treated PUR plastics was destroyed with an eroded morphology. Contact angle and thermogravimetry analysis (TGA) showed that the hydrophilicity of PUR plastics increased along with decreased thermal stability upon treatment by strain G-11, which were consistent with the weight loss and morphological observation. These results indicated that strain G-11 isolated from landfill has potential application in biodegradation of waste PUR plastics.
Plastics/metabolism*
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Polyurethanes/chemistry*
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RNA, Ribosomal, 16S
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Bacteria/genetics*
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Biodegradation, Environmental
7.Optimized multi-scale entropy to localize epileptogenic hemisphere of temporal lobe epilepsy based on resting-state functional magnetic resonance imaging.
Chong XIE ; Manling GE ; Xiaoxuan FU ; Shenghua CHEN ; Fuyi ZHANG ; Zhitong GUO ; Zhiqiang ZHANG
Journal of Biomedical Engineering 2021;38(6):1163-1172
Entropy model is widely used in epileptic electroencephalogram (EEG) analysis, but there are few reports on how to objectively select the parameters to compute the entropy model in the analysis of resting-state functional magnetic resonance imaging (rfMRI). Therefore, an optimization algorithm to confirm the parameters in multi-scale entropy (MSE) model was proposed, and the location of epileptogenic hemisphere was taken as an example to test the optimization effect by supervised machine learning. The rfMRI data of 20 temporal lobe epilepsy (TLE) patients with hippocampal sclerosis, positive on structural magnetic resonance imaging, were divided into left and right groups. Then, the parameters in MSE model were optimized by the receiver operating characteristic curves (ROC) and area under ROC curve (AUC) values in sensitivity analysis, and the entropy value of the brain regions with statistically significant difference between the groups were taken as sensitive features to epileptogenic hemisphere lateral. The optimized entropy values of these bio-marker brain areas were considered as feature vectors input into the support vector machine (SVM). Finally, combining optimized MSE model with SVM could accurately distinguish epileptogenic hemisphere in TLE at an average accuracy rate of 95%, which was higher than the current level. The results show that the MSE model parameter optimization algorithm can accurately extract the functional imaging markers sensitive to the epileptogenic hemisphere, and achieve the purpose of objectively selecting the parameters for MSE in rfMRI, which provides the basis for the application of entropy in advanced technology detection.
Brain/diagnostic imaging*
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Brain Mapping
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Entropy
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Epilepsy, Temporal Lobe/diagnostic imaging*
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Humans
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Magnetic Resonance Imaging
8.Effects of Zishen Yutai Pills on expression of Bcl-2 and Bax in rat model of diminished ovarian reserve
Si CHEN ; Yaohua FAN ; Jing LI ; Ying ZHAO ; Zhitong ZHANG ; Ziying LI ; Yinghui CHEN
Chongqing Medicine 2018;47(14):1853-1856,1861
Objective To investigate the effect of Zishen Yutai Pills on follicle apoptosis and related protein expression in diminished ovarian reserve(DOR) rat model induced by tripterygium glycosides.Methods Forty rats were divided into the control group,model group,progynova group,and Zishen Yutai Pills high and low dose groups,8 cases in each group.Tripterygium Wilfordii Glycosides Tablets were given by gavage for establishing the rat DOR model.Then the HE staining was used to detect the pathological morphology of rat ovary.All levels of follicles were counted.Expression levels of Bcl-2 and Bax protein in follicle and ovarian stroma of each group were detected by using the immunohistochemical method.Results Compared to the control group,the number of great and small follicles in the model control group was decreased,number of atretic follicles was increased,Bcl-2 expression in all kinds of follicles was decreased,and Bax expression was increased,the differences were statistically significant(P<0.05).Compared to the model group,the number of great and small follicles in the Zishen Yutai Pills high and low dose groups and progynova group was increased,number of atretic follicles was decreased,the Bcl-2 expression in great and small follicles was significantly increased and the Bax expression was significantly decreased,the differences were statistically significant(P<0.05).Conclusion Zishen Yutai Pills can inhibit the premature and too fast follicles apoptosis by upregulating the expression of Bcl-2 protein and down-regulating the expression of Bax protein,thus plays the effect for treating DOR.
9.Effect of ultra-early stent-assisted coil embolization on ruptured intracranial aneurysms
Jianwu LONG ; Jinlong CHEN ; Xueyang HE ; Hongqi ZHANG ; Zhitong GUO
Chinese Journal of Cerebrovascular Diseases 2016;(2):95-99
Objective To investigate the therapeutic effect of the ultra-early stent-assisted coil embolization of the ruptured intracranial aneurysms. Methods The clinical data of 13 patients with ruptured intracranial aneurysm treated by ultra-early stent-assisted coil embolization were analyzed retrospectively. The preoperative Hunt-Hess gradeⅠ-Ⅱ was in 7 cases,gradeⅢ was in 4 cases,and grade Ⅳ was in 2 cases. The patients were treated with stent-assisted coil embolization under the general anesthesia with endotracheal intubation within 24 h of aneurysm rupture. The postoperative embolization was assessed according to the Raymond grading standard. The postoperative complications and the assessment of the follow-up results from 1 to 6 months after procedure according to the modified Rankin scale (mRS ) scores were observed. Results All 11 patients recovered well,1 case had postoperative hemiplegia,1 case had postoperative bleeding,and none of them died. During the follow-up period,no patients had rebleeding, 1 had recurrence,and DSA revealed that the patient was embolized completely at 2 months after reembolization. Conclusion The method of ultra-early stent-assisted coil embolization of ruptured intracranial aneurysms is feasible. It may improve the cure rate of the ruptured aneurysms and improve the prognosis of patients.
10.Effect of Rehabilitation Medical Professional Training in Guangzhou, China
Zhou XING ; Zhitong LIN ; Cuihuan PAN ; Yan CHEN ; Rui YU ; Yu ZHOU ; Zhengmao YE ; Zhen FU
Chinese Journal of Rehabilitation Theory and Practice 2015;21(3):370-372
Objective To investigate the effect of rehabilitation professional training. Methods Based on the 10 tertiary hospitals in Guangzhou, Guangdong, the professionals from communitiy hospitals were trained. The scores of knowledge and practice tests were analyzed in 2 terms of training. Results The students performed better in the practice test (82.01±8.91) than knowledge (71.08±10.05) (P<0.01). The score of knowledge tests was better in the second term than the first (P<0.05), no difference between them in the score of practice test. Conclusion Rehabilitation professional training in Guangzhou can improve the ability of service of medical rehabilitation.


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