1.Construction of micropapillary lung adenocarcinoma organoids and screening of targeted drugs
Zhongmin JIANG ; Chunyan ZHANG ; Min LIU ; Jie ZHENG ; Yanxia LI ; Qingcuo REN ; Wei MENG ; Xiaozhi LIU
Tianjin Medical Journal 2024;52(1):22-27
Objective To establish a culture method for micropapillary lung adenocarcinoma organoids and conduct targeted drug screening.Methods Organoids were extracted and cultured from a surgical tissue sample of a patient diagnosed with micropapillary lung adenocarcinoma,and the growth of lung cancer organoids was observed and recorded dynamically.The morphological and gene expression characteristics of tumor cells between lung cancer organoids and parental tissue were compared using hematoxylin eosin(HE)staining and immunohistochemical methods.Real time fluorescence quantitative polynucleotide chain reaction(qRT-PCR)method was used to detect gene mutations in lung cancer parental tissue and organoids.Finally,based on results of genetic testing,targeted drugs were selected and their therapeutic effects were verified.Results We have successfully cultured spherical organoids from micropapillary lung adenocarcinoma tissue,which can be passaged for at least 3 generations.HE staining results showed that the morphology of tumor cells in organoids was roughly consistent with that of parental tissue.The immunohistochemical results showed that the protein expression levels of various genes in lung cancer organoids and parental tissue were roughly the same.Results of gene mutation analysis showed that the mutated genes in lung cancer parental tissue and organoids were consistent,both reflecting RET fusion.The screening results of targeted drugs based on lung cancer organoids showed that vandertinib had the best anti-tumor effect in vitro.Conclusion Drug screening experiments based on micropapillary lung adenocarcinoma organoids can screen highly efficient targeted drugs in a short period of time,which may benefit patients with micropapillary lung adenocarcinoma.
2.Exploring the characteristics changes of cardiopulmonary exercise testing in patients with acute coronary syndrome after PCI before and during the COVID-19 pandemic
Xingbo MU ; Qiang REN ; Yushan LI ; Jian ZHANG ; Yanchun LIANG ; Yanxia WANG ; Quanyu ZHANG ; Yaling HAN
Chinese Journal of Cardiology 2024;52(9):1065-1072
Objective:To investigate the changes in cardiopulmonary exercise testing (CPET) characteristics before and after the outbreak of COVID-19 in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI).Methods:This is a cross-sectional study that included ACS patients who underwent PCI at the General Hospital of the Northern Theater Command from July 2018 to February 2023. Based on the timeline of the COVID-19 pandemic, patients were divided into two groups: the pre-pandemic group and the during-pandemic group, with January 2020 as the dividing line. Clinical data were collected from both groups, and a comparative analysis was performed on their postoperative CPET outcomes, including peak oxygen uptake (peak VO 2), peak metabolic equivalents (peak MET), and other indicators. Weber′s classification was used to assess cardiac function. In addition, the 7-tiem generalized anxiety disorder scale (GAD-7) and the patient health questionnaire-9 (PHQ-9) were used to assess the patients′ psychological anxiety and depression states, respectively. Multivariate logistic regression was used to analyze the influencing factors of CPET after PCI. Results:A total of 4 310 post-PCI ACS patients were included, with an average age of (58.7±9.1) years, and 3 464 (80.37%) were male. There were 1 698 patients in the pre-pandemic group and 2 612 patients in the during-pandemic group. The main indicator of the CPET, peak VO 2 (15.04±3.93) ml·min -1·kg -1 in the during-pandemic group, was lower than that in the pre-pandemic group (15.52±3.68) ml·min -1·kg -1, and the difference was statistically significant ( P<0.001). Multivariate logistic regression analysis showed that advanced age, female gender, high body mass index, elevated high-sensitivity C-reactive protein, reduced high-density lipoprotein cholesterol, smoking history, history of myocardial infarction, more severe ACS classification, and mild to moderate degree of depression were related to poor cardiopulmonary outcomes ( P<0.05). Conclusion:The COVID-19 pandemic had a negative impact on the cardiopulmonary outcomes of ACS patients after PCI. Reduced physical activity, and increased psychological stress should be given consideration and attention regarding their impact on patients′ cardiopulmonary function.
3.Overexpression of mitoNEET inhibits ferroptosis-induced mitochondrial metabolic dysfunction in brown adipocytes
Hongyu ZHENG ; Zhen TIAN ; Yanxia WANG ; Kun ZHOU ; Zhong REN ; Zhixiang ZHOU ; Wenhao XIONG ; He ZHENG ; Zhisheng JIANG
Chinese Journal of Pathophysiology 2024;40(5):852-861
AIM:To investigate the potential impact of mitoNEET[mitochondrial protein containing Asn-Glu-Glu-Thr(NEET)sequence]on mitochondrial metabolism in brown adipocytes,and to elucidate its underlying mecha-nism.METHODS:An in vitro model of primary mouse brown adipocytes was established.Western blot were utilized to detect relevant proteins,and iron ion and ATP content was measured using kits.Mitochondrial membrane potential and re-active oxygen species(ROS)were assessed by fluorescence microscopy and flow cytometry.RESULTS:The expression of the ferroptosis-related protein ACSL4 increased by 1.13 times in ferroptosis inducer erastin treatment group,whereas the expression of SLC7A11 and GPX4 decreased by 27.33%and 25.33%,respectively,compared with control group(P<0.05).The expression of Nrf1,PGC-1α,MFN2 and UCP1 proteins,related to mitochondrial energy metabolism,de-creased by 20.98%,15.17%,15.03%and 34.22%,respectively(P<0.05).Additionally,the mitoNEET protein con-tent was significantly reduced by 42.14%(P<0.05).The iron ion content in erastin group was substantially increased by 1.80 times compared with control group.However,a notable decrease in ATP content of 14.95%was seen(P<0.05).The results obtained from fluorescence microscopy and flow cytometry demonstrated a significant decrease in the mitochon-drial membrane potential of brown adipocytes in erastin group,with reductions of 52.18%and 61.31%(P<0.05),re-spectively.A substantial increase in mitochondrial ROS content of 80.97%was seen(P<0.05).Western blot analysis of overexpressed stable strains revealed a significant elevation in mitoNEET levels in brown adipocytes following lentivirus transfection,exhibiting an increase of 11.19 times(P<0.05),thus confirming successful transfection.The LV-mitoNEET group exhibited a significant decrease of 37.95%in the expression of ferroptosis-related protein ACSL4 in brown adipose cells compared with control group.Additionally,there was a notable increase of 77.82%and 66.3%in the expression of SLC7A11 and GPX4,respectively(P<0.05).Up-regulation was observed in the expression of MFN2(79.06%),PGC-1α(72.89%),Nrf1(40.14%),and UCP1(31.68%)(P<0.05).The test results demonstrated that the LV-mitoNEET group experienced a reduction of 43.5%in iron ion content compared with control group while exhibiting an increase of 33.5%in ATP content(P<0.05).The results obtained from fluorescence microscopy and flow cytometry demonstrated that mitoNEET overexpression led to a significant increase in the mitochondrial membrane potential of erastin-induced brown adipocytes,with increments of 17.61%and 96.05%,respectively.Additionally,mitoNEET overexpression effec-tively reduced the production of mitochondrial ROS by 24.48%(P<0.05).CONCLUSION:Our findings suggest that mitoNEET overexpression can effectively inhibit the disruption of mitochondrial energy metabolism caused by ferroptosis-induced death of brown adipocytes.
4.Effect of osimertinib combined with aspirin on survival period in advanced lung adenocarcinoma patients with EGFR mutation
Yan LUO ; Lan YAO ; Zhonghui BAO ; Yi JIANG ; Yanxia NI ; Qin HUANG ; Shaolin LI ; Hongbo REN ; Biyou HUANG
Chongqing Medicine 2024;53(13):2011-2015
Objective To investigate the effect of osimertinib combined with aspirin on the survival pe-riod of the advanced lung adenocarcinoma patients with epidermal growth factor receptor(EGFR)mutation.Methods Sixty lung adenocarcinoma patients with EGFR mutation in advanced non-small cell lung cancer(NSCLC)first diagnosed in Banan District Second People's Hospital of from August 2020 to October 2021 were selected as the study subjects and divided into the observation group and control group by the random number table method,30 cases in each group.The observation group adopted osimertinib combined with aspi-rin,and the control used osimertinib merely.The overall response rate(ORR),disease control rate(DCR),progression-free survival(PFS),overall survival(OS)and the adverse reactions occurrence were compared between the two groups.Results ORR and DCR after 3,6,12 months medication in the observation group were higher than those in the control group,but the differences were not statistically significant(P>0.05).Compared with the control group,PFS and OS in the observation group were longer,and the differences were statistically significant[14.9(11.8,17.2)m vs.10.5(8.9,12.5)m;24.1(19.5,27.4)m vs.18.1(16.1,21.1)m,P<0.05].In addition,PFS and OS in male and female patients with brain metastasis,EGER19 and 21 ex-on mutation in the observation group were longer than those in the control group,and the differences were statistically significant(P<0.05).There was no statistically significant difference in overall and≥Ⅲ degree adverse reactions between the two groups(P>0.05).Conclusion Osimertinib combined with aspirin could prolong PFS and OS of the advanced lung adenocarcinoma patients with EGFR mutation without increasing the risk of adverse reactions.
5.Advances in Imaging of Interstitial Lung Disease in Connective Tissue Diseases
Yanxia SHI ; Hongbin LI ; Tingting REN ; Rongxia NING
Chinese Journal of Medical Imaging 2024;32(9):961-965
Interstitial lung disease is a common lung disease of connective tissue disease,which seriously affects the survival rate and quality of life of patients with connective tissue disease.Interstitial lung disease may occur in the whole course of connective tissue disease.Therefore,imaging plays an important role in the whole disease cycle of connective tissue-associated interstitial lung disease.At present,high-resolution computed tomography is the cornerstone of screening,diagnosis and follow-up of connective tissue-associated interstitial lung disease,but ionizing radiation is a potential limiting factor in its clinical application.In recent years,new imaging techniques have developed rapidly,and some promising research results have been achieved in the early screening,diagnosis and efficacy evaluation of connective tissue-associated interstitial lung disease,and they are gradually moving towards non-invasive,low-radiation and accurate imaging analysis techniques.This article reviews the advances in imaging research of connective tissue-associated interstitial lung disease,and analyzes the advantages and disadvantages of various new imaging techniques,as well as the challenges and prospects.
6.Clinical characterization and genetic analysis of 5 Chinese families with glucokinase gene mutations
Yuansi CHEN ; Mingwei SHAO ; Gaofei REN ; Duo CHEN ; Feng GUO ; Yanxia LIU ; Zhizhen LI ; Liangge SUN ; Guijun QIN
Chinese Journal of Endocrinology and Metabolism 2022;38(8):645-650
Objective:To summarize the clinical manifestations and molecular genetic characteristics of 5 families with maturity-onset diabetes mellitus of the young 2 (MODY2) caused by glucokinase (GCK) gene mutations.Methods:Clinical data and biochemical results of probands were collected. Peripheral blood samples of probands and first-degree family members were collected and whole exome gene was detected using second-generation sequencing. After comparing against the database, the suspected pathogenic sites were selected for Sanger sequencing verification.Results:All the 5 probands presented with mild fasting hyperglycemia, HbA 1C<7.5%, and no symptoms of thirst, polydipsia or polyuria. There were 6 mutants in 5 families, including M1: c.555delT (P.leu186CysFS Ter19) and M3: c. 263T>A (p.Met88Lys) which haven′t been reported before. During the follow-up, all probands received life-style intervention, except 2 pregnant women who should consider insulin treatment if necessary according to fetal genotypes. Conclusion:Among patients who meet the diagnostic criteria for MODY, MODY2 screening should be performed for children or pregnant women with mild hyperglycemia and family history. GCK gene detection is the gold standard for diagnosis, and accurate diagnosis will be conducive to the selection of appropriate treatment.
7.Breast ultrasound optimization process analysis based on breast cancer screening for 1 501 753 rural women in China
Lan MA ; Zhenqiang LIAN ; Yanxia ZHAO ; Jiangli DI ; Bo SONG ; Wenhui REN ; Huazhang MIAO ; Jiuling WU ; Qi WANG
Chinese Journal of Oncology 2021;43(4):497-503
Objective:To evaluate the effectiveness and quality of ultrasound-based (BUS) process optimization in breast cancer screening.Methods:The program collected the first to fourth quarterly breast cancer screening statistic data and case report data from 30 provinces, autonomous regions and municipalities in 2015 by the online report system of national key service program of women and children′s public health. The call rate, mammography (MG) subsequent screen rate, biopsy rate, detection rate, early diagnosis rate, carcinoma in situ rate, missing detection rate, false positive rate and positive predictive value (PPV) of breast cancer were calculated.Results:A total of 1 501 753 rural women attended the BUS process optimization screening. The nationwide recall rate was 3.01%(45 156/1 501 753), and in the eastern and central area were 3.41%(17 173/503 130) and 3.56%(14 499/407 739), respectively, higher than 2.28% (13 484/590 884) of western area ( P<0.05). The nationwide MG subsequent screen rate was 2.78%(41 694/1 501 753), and in the eastern and central area were 3.19%(16 036/503 130) and 3.29% (13 421/407 739), respectively, higher than 2.07%(12 237/590 884) of western area ( P<0.05). The nationwide biopsy rate was 0.23%(3 462/1 501 753), and in the central area were 0.26%(1 078/407 739), respectively, higher than 0.21%(1 247/590 884) of western area and 0.23% (1 137/503 130) of eastern area ( P<0.05). The nationwide biopsy PPV was 37.00%(1 281/3 462). The biopsy PPV of eastern area was (34.30%, 390/1 137), lower than 39.33% (424/1 078) of central area ( P<0.05). A total of 1 281 cases of breast cancer were detected, the detection rate was 0.85‰(1 281/1 501 753), and the detection rates of central area was 1.04‰ (424/407 739), higher than 0.79‰(467/590 884) of western area and 0.78‰(390/503 130) of eastern area ( P<0.05). The BUS initiate screening positive rate from detected breast cancer cases was 96.96%(1 242/1 281), the MG subsequent screening positive rate was 2.42%(31/1 281). The nationwide early diagnosis rate was 85.25%(1 092/1 281), and in the eastern and central areas were 87.95%(343/390) and 88.21%(374/424), higher than 80.30%(375/467) of western area ( P<0.05). The screening rate of on or above stage Ⅱ breast cancer in eastern area was 55.64%(217/390), lower than 64.62%(374/424) of central area and 62.31%(291/467) of western area. The missing detection rate was 0.62%(8/1 281) and false positive rate was 1.20%(17 528/1 464 149). Conclusions:The BUS process optimization of breast cancer screening scheme is reasonable and applicable to China rural women. The effectiveness and quality of eastern area are superior to those of central and western area.
8.Breast ultrasound optimization process analysis based on breast cancer screening for 1 501 753 rural women in China
Lan MA ; Zhenqiang LIAN ; Yanxia ZHAO ; Jiangli DI ; Bo SONG ; Wenhui REN ; Huazhang MIAO ; Jiuling WU ; Qi WANG
Chinese Journal of Oncology 2021;43(4):497-503
Objective:To evaluate the effectiveness and quality of ultrasound-based (BUS) process optimization in breast cancer screening.Methods:The program collected the first to fourth quarterly breast cancer screening statistic data and case report data from 30 provinces, autonomous regions and municipalities in 2015 by the online report system of national key service program of women and children′s public health. The call rate, mammography (MG) subsequent screen rate, biopsy rate, detection rate, early diagnosis rate, carcinoma in situ rate, missing detection rate, false positive rate and positive predictive value (PPV) of breast cancer were calculated.Results:A total of 1 501 753 rural women attended the BUS process optimization screening. The nationwide recall rate was 3.01%(45 156/1 501 753), and in the eastern and central area were 3.41%(17 173/503 130) and 3.56%(14 499/407 739), respectively, higher than 2.28% (13 484/590 884) of western area ( P<0.05). The nationwide MG subsequent screen rate was 2.78%(41 694/1 501 753), and in the eastern and central area were 3.19%(16 036/503 130) and 3.29% (13 421/407 739), respectively, higher than 2.07%(12 237/590 884) of western area ( P<0.05). The nationwide biopsy rate was 0.23%(3 462/1 501 753), and in the central area were 0.26%(1 078/407 739), respectively, higher than 0.21%(1 247/590 884) of western area and 0.23% (1 137/503 130) of eastern area ( P<0.05). The nationwide biopsy PPV was 37.00%(1 281/3 462). The biopsy PPV of eastern area was (34.30%, 390/1 137), lower than 39.33% (424/1 078) of central area ( P<0.05). A total of 1 281 cases of breast cancer were detected, the detection rate was 0.85‰(1 281/1 501 753), and the detection rates of central area was 1.04‰ (424/407 739), higher than 0.79‰(467/590 884) of western area and 0.78‰(390/503 130) of eastern area ( P<0.05). The BUS initiate screening positive rate from detected breast cancer cases was 96.96%(1 242/1 281), the MG subsequent screening positive rate was 2.42%(31/1 281). The nationwide early diagnosis rate was 85.25%(1 092/1 281), and in the eastern and central areas were 87.95%(343/390) and 88.21%(374/424), higher than 80.30%(375/467) of western area ( P<0.05). The screening rate of on or above stage Ⅱ breast cancer in eastern area was 55.64%(217/390), lower than 64.62%(374/424) of central area and 62.31%(291/467) of western area. The missing detection rate was 0.62%(8/1 281) and false positive rate was 1.20%(17 528/1 464 149). Conclusions:The BUS process optimization of breast cancer screening scheme is reasonable and applicable to China rural women. The effectiveness and quality of eastern area are superior to those of central and western area.
9.Psychological needs of severe mentally ill persons during closed hospital treatment
Yanxia REN ; Kun YANG ; Lian XUE ; Baodong WANG
Chinese Journal of Modern Nursing 2020;26(11):1425-1428
Objective:To understand the psychological needs of severe mentally ill persons under closed management during hospitalization.Methods:From March 2017 to March 2018, a total of 81 severe mentally ill persons under closed management in Sichuan Mental Health Center were selected as research objects by the convenience sampling method. A self-designed questionnaire for the psychological needs of severe mentally ill persons was used to investigate the psychological needs of patients such as self-awareness, self-attribution of hospitalization and problems they wish to solve and to analyze the influencing factors of psychological needs of patients.Results:Among the 81 patients, 33.33% (27/81) thought that they were ill. For this hospitalization, 39.51% (32/81) of the patients attributed to their personality and 17.28% (14/81) attributed to emotional problems. Among the psychological needs, 79.01% (64/81) wished to be accompanied and visited by family members, and 62.96% (51/81) required psychological treatment. Among the most wanted problems, 35.80% (29/81) hoped to cure the disease and only 4.94% (4/81) wanted to improve self-confidence. Patients diagnosed with different diseases had statistically significant differences in their needs for family accompany, and visitation ( P<0.05) . Patients of different genders have statistically significant differences in the needs of their own disease-related knowledge ( P<0.05) . There was a statistically significant difference in patients with different educational levels in improving stress coping ability ( P<0.05) . Conclusions:Severe mentally ill persons under closed management during hospitalization have more psychological needs with different genders, educational levels, and different disease diagnosis. Therefore, it is necessary to provide targeted psychological intervention and nursing to promote the recovery of patients as soon as possible.
10.Clinical Observation of Sanjiao Fuzheng Mixture Combined with Concurrent Chemoradiotherapy of Paclitaxel and Nedaplatin in the Treatment of Local Advanced Non-small Cell Lung Cancer
Yi RAN ; Dongmei XIA ; Zhonghui BAO ; Hongbo REN ; Yi JIANG ; Jifan YANG ; Biyou HUANG ; Lan YAO ; Yanxia NI ; Shaolin LI
China Pharmacy 2018;29(10):1377-1380
OBJECTIVE:To observe the efficacy and safety of Sanjiao fuzheng mixture combined with concurrent chemoradiotherapy of paclitaxel and nedaplatin in the treatment of local advanced non-small cell lung cancer (NSCLC). METHODS:A total of 68 patients with local advanced NSCLC selected from our hospital during Jan. 2015 to Jan. 2017 were divided into control group and observation group according to random number table,with 34 cases in each group. Control group was given Paclitaxel injection 135 mg/m2 intravenously,d1+Nedaplatin for injection 75 mg/m2 intravenously,d3,21 d as a treatment course,for 2 courses;routine fractionated intensity modulated radiation therapy,2 Gy each time,5 times a week,60-70 Gy in total;given 2 cycles of primary chemotherapy continuously after radiotherapy. Observation group was additionally given Sanjiao fuzheng mixture 250 mL/d,divided into 3 times,till the end of treatment,on the basis of control group. Clinical efficacies were observed in 2 groups. The levels of nutritional indexes (BMI,PAB,ALB,Hb) and tumor markers (SCC-Ag,CEA,TK1, CYFRA21-10) before and after treatment were observed. The occurrence of ADR were recorded. RESULTS:There was no statistical significance in the total effective rate between 2 groups (observation group 82.35% vs. control group 73.53%)(P>0.05). After treatment,the levels of BMI,PAB,ALB and Hb in 2 groups were significantly lower than before treatment,but the observation group was significantly higher than the control group. The levels of SCC-Ag,CEA,TK1 and CYFRA21-1 in 2 groups were significantly lower than before treatment,and the observation group was significantly lower than the control group,with statistical significance (P<0.05). The incidence of Ⅲ-Ⅳ degree aleucocytosis,Ⅰ-Ⅱ degree hemoglobin reduction and thrombocytopenia in observation group were significantly lower than control group, with statistical significance (P<0.05). CONCLUSIONS:The efficacy of Sanjiao fuzheng mixture combined with concurrent chemoradiotherapy of paclitaxel and nedaplatin is similar to that of concurrent chemoradiotherapy of paclitaxel and nedaplatin for localadvanced NSCLC,which can improve nutritional status significantly,and reduce the incidence of ADR.

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