1.EGFR-TKI Combined with Pemetrexed versus EGFR-TKI Monotherapy in Advanced EGFR-mutated NSCLC: A Prospective, Randomized, Exploratory Study
Weiguang GU ; Hua ZHANG ; Yiyu LU ; Minjing LI ; Shuang YANG ; Jianmiao LIANG ; Zhijian YE ; Zhihua LI ; Minhong HE ; Xiaoliang SHI ; Fei WANG ; Dong YOU ; Weiquan GU ; Weineng FENG
Cancer Research and Treatment 2023;55(3):841-850
Purpose:
We aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)–mutated patients with or without concomitant alterations.
Materials and Methods:
This multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non–small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR–tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint.
Results:
The overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment.
Conclusion
EGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.
2.Perioperative nursing characteristics and management of oral cancer patients underwent radical resection and flap reconstrution
Liping ZHANG ; Juan WU ; Qiuling LIU ; Youyuan WANG ; Minhong HUANG ; Jinjuan LIU
Chinese Journal of Practical Nursing 2022;38(26):2037-2043
Objective:To analyze the perioperative clinical characteristics of patients with oral cancer underwent radical resection and flap reconstrution and the nursing managements.Methods:From January 2020 to December 2020, 658 patients with oral cancer underwent radical resection and flap reconstrution in the Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University were retrospectively analyzed. All patients were divided into the elderly group (≥60 years) and the younger group (< 60 years), including 279 cases in the elderly group and 379 cases in the younger group. The perioperative clinical data of the patients were collected, and the perioperative general situation, postoperative complications and influencing factors of complications were analyzed.Results:There were differences between the two groups in the aspects of sex ( χ2 = 12.38, P<0.001), preoperative BMI ( t = 2.43, P = 0.015), smoking history ( χ2 = 18.34, P<0.001), preoperative anesthesia grade ( χ2 = 25.61, P = 0.001), preoperative coexisting disease ( χ2 = 46.97, P<0.001), whether oral floor or tongue cancer ( χ2 = 16.68, P<0.001), whether free flap ( χ2 = 6.81, P = 0.003), operation time ( t = 2.19, P = 0.029), preoperative test index hemoglobin ( t = 4.96, P<0.001), albumin ( t = 5.44, P<0.001), D-dimer( Z = -13.52, P<0.001), calcium levels ( t = 4.07, P<0.001) and postoperative complications ( χ2 = 14.55, P<0.001). Multivariate analysis of postoperative complications showed that the age ( OR = 1.021, 95% CI = 1.005-1.037, P = 0.011), preoperative D-dimer ( OR = 1.219, 95% CI = 1.026-1.447, P = 0.024) and the preoperative coexisting disease ( OR = 1.642, 95% CI = 1.108-2.432, P = 0.013) were the risk factors for the postoperative complications. Multivariate analysis of discharge with tube showed that the age ( OR = 1.017, 95% CI = 1.003-1.031, P = 0.017), preoperative BMI ( OR = 0.917, 95% CI = 0.873-0.963, P = 0.001), whether oral floor or tongue cancer ( OR = 2.135, 95% CI = 1.475-3.091, P<0.001), and operation time ( OR = 1.220, 95% CI = 1.120-1.328, P<0.001) were the related factors for the discharge with tube. Conclusion:In view of the above risk factors, it is beneficial for the physical and mental recovery of patients to pay attention to preoperative evaluation, make adequate preoperative preparation, postoperative nursing and observation, improve swallowing function training, prepare for discharge, pay attention to continuous nursing, and establish a tertiary hospital-community-family rehabilitation system.
3.Clinicopathological features of polymorphous low-grade neuroepithelial tumor of the young
Sha ZHAO ; Juan WANG ; Mingna LI ; Ying DING ; Minhong PAN ; Kun SONG
Chinese Journal of Pathology 2022;51(7):640-646
Objective:To investigate the clinicopathological features and differential diagnosis of polymorphous low-grade neuroepithelial tumor of the young (PLNTY).Methods:Five cases of PLNTY diagnosed at the First Affiliated Hospital and Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China from 2019 to 2021 were collected. All cases were evaluated using clinical and imaging data, histology, immunohistochemical staining and molecular genetics. The relevant literature was reviewed.Results:There were two male and three female patients, aged 10 to 39 years, with an average age of 25 years. Clinically, the tumors were in the temporal lobe (3 cases), the lateral ventricle (1 case) and the left head of caudate nucleus (1 case). The clinical manifestations included epilepsy in 3 cases, right visual disturbance in 1 case, and post-trauma incidental finding in 1 case. Microscopically, the lesions were characterized with infiltrative growth, cellular pleomorphism (oligodendroglioma-like cells were always present, with low-grade, pleomorphic nuclei) and variable calcifications. Immunohistochemically, the tumor cells were positive for GFAP and Olig2. They also showed intense and diffuse expression of CD34 while CD34 expressing ramified neural elements were present in regional cortex. Ki-67 proliferation index was less than 3%. Molecular genetics showed the BRAF V600E mutation in 2 cases, the PAK5-Q337R missense mutation in 1 case, the FGFR2-CTNNA3 fusion in 1 case, and the FGFR2-INA and FGFR2-PPRC1 concomitant fusion in 1 case. No postoperative chemoradiotherapy was given. Follow-up intervals ranged from 3 to 29 months while no recurrence or metastasis was identified.Conclusions:PLNTY is uncommon. A definite diagnosis of PLNTY relies on histopathological examination and molecular genetics. It is important to distinguish PLNTY from high grade gliomas and avoid overtreatment. The recently reported the PAK5-Q337R missense mutation and the FGFR2-PPRC1 gene fusion in PLNTY may help diagnose and understand the pathogenesis of PLNTY.
4.Effect of inhaled budesonide on the prevention of bronchopulmonary dysplasia in premature infants and its impact on the development of intelligence at 1 year old
Qian XYU ; Shunxian ZHANG ; Lirong LUO ; Hongli WANG ; Minhong XU ; Shaowei YU
Journal of Public Health and Preventive Medicine 2021;32(2):77-80
Objective To evaluate potential protective effects of inhaled budesonide on bronchopulmonary dysplasia (BPD) in premature infants and its impact on the intelligence development at 1 year of age. Methods A total of 82 preterm infants admitted to the neonatal intensive care center from January 2017 to January 2018 were selected as research subjects. The enrolled subjects were divided into a study group (Budesonide) and a control group (saline) by random number table method, with 41 cases in each group. The incidence of BPD, mortality, hospitalization time, time of withdrawal and oxygenation, and complications were compared between the two groups. The patients were regularly followed up to 1 year old after discharge. The physical growth and Gesell intelligence development of the two groups were compared. Results The incidence of BPD in the study group was significantly lower than that in the control group, and the difference was statistically significant (P<0.05). There was no significant difference in mortality between the two groups. The hospitalization time, weaning and oxygenation time, and 1-week re-intubation rate in the study group were significantly lower than those in the control group (P<0.05). There was no significant difference between the two groups in the incidence of adverse reactions and physical growth at 1 year old and Gesell intelligence evaluation. Conclusion Budesonide aerosol inhalation reduced the incidence of BPD in premature infants, shortened hospitalization and weaning time, and there were no near-term and long-term adverse reactions.
5.Effect of berberine on alveolar bone absorption in diabetic rats
International Journal of Biomedical Engineering 2020;43(3):171-176
Objective:To study the effect and mechanism of berberine intervention on alveolar bone absorption in diabetic rats.Methods:Diabetes rat model was established by one-time intraperitoneal injection of streptozotocin (35 mg/kg). Sixty healthy female Sprague-Dawley rats without specific pathogens were divided into normal group, diabetic group and berberine group according to the random number table method, 20 rats for each group. The rat models in the berberine group and the diabetic group were given berberine (200 mg/kg) and an equal volume of sodium chloride injection by gavage, once a day, for 4 consecutive weeks. The rat models in the normal group were not treated. Fasting blood glucose (FBG), fasting insulin level (Fins) , hormone resistance index (HOMA-IR) and insulin sensitivity index (ISI), as well as the serum calcium, phosphorus content, alkaline phosphatase activity and osteocalcin content of the rats were measured. The pathological changes of periodontal tissues were detected by HE staining. The expression of BMP-2/Smad pathway (BMP-2, Smad1, Smad4) was detected by RT-PCR and Western blot.Results:Compared with the diabetes group, the FBG level of rats in the berberine group [(9.88±1.23) mmol/L vs. (21.66±2.41) mmol/L], Fins levels [(11.63±3.63) mIU/L vs. (21.64±5.58) mIU/L] , HOMA-IR (7.58±0.96 vs. 20.85±1.95) were reduced, and ISI (-5.10±0.16 vs. 6.15±0.18), serum calcium levels[(1.855±0.125) mmol/L vs. (1.317±0.104)) mmol/L], serum phosphorus levels [(3.087±0.278) mmol/L vs. (2.526±0.226) mmol/L], serum ALP levels [(130.681±18.963) U/L vs. (99.874±31.968) U/L] and osteocalcin levels [(112.368±9.752) ng/ml vs. (78.645±10.973) ng/ml] were all increased, and the differences were statistically significant (all P<0.05). The results of hematoxylin-eosin staining showed that there was no bone resorption in the alveolar bone of the rats in the normal group, bone resorption was found in the alveolar bone of the rats in the diabetes group, and the bone resorption of the alveolar bone in the berberine group was significantly reduced. RT-PCR and Western Blot results showed that compared with the diabetes group, the BMP-2, Smad1, Smad4 gene mRNA and protein in the alveolar bone tissue of the berberine group were significantly increased (all P<0.05). Conclusions:Berberine intervention can reduce FBG levels in diabetic rats and improve insulin resistance, which may reduce alveolar bone resorption in diabetic rats by up-regulating the BMP-2/Smad signaling pathway.
6.Conventional MRI texture analysis of peritumoral edema in the differential diagnosis of glioblastoma and solitary metastatic brain tumor
Chinese Journal of Radiology 2018;52(10):756-760
Objective To investigate the value of conventional MR texture analysis of peritumoral edema in differentiating between glioblastoma and solitary metastatic brain tumor. Methods Forty patients with brain glioma and forty patients with brain metastases confirmed by pathology or clinic were enrolled . All patients underwent conventional MRI scan and enhanced examination, including axial T1WI, T2WI, fluid attenuated inversion recovery(FLAIR) and enhanced T1WI. The ROI was manually outlined by MaZda software in the most obvious level of 4 sequences of peritumoral edema and the texture features were extracted, including mean, variance, skewness, kurtosis, 1 percentile, 10 percentile, 50 percentile, 90 percentile, 99 percentile. Independent sample t-test (in case of normality and variance homogeneity test) or rank sum test (in case of not satisfying normality and homogeneity of variance) was used to compare the differences of the histogram parameters and to make meaningful parameters based on logistic regression modeling and drawing the receiver operating characteristic curve (ROC curve) to evaluate the differential diagnosis efficacy. Results Through the preliminary feature screening, skew of FLAIR (SkewFLAIR) for glioblastomas was -0.358±0.432, respectively,while for solitary metastatic brain tumor, the statistics was-0.648 ± 0.503. The results showed statistically significant difference(t=7.574,P=0.006). The differencesbetween the kurtosis (KurtFLAIR) were also proven to be statistically significant (Z=4.360 ,P=0.037),with-0.384 (-0.798, 0.049) for glioblastomas and-0.089 (-0.456, 0.613) for solitary metastasis brain tumor. The sensitivity of the corresponding logistic regression differential diagnosis model was 77.5%, specificity was 94.3%, and area under the curve (AUC) was 0.85. Conclusion Conventional MRI texture analysis of peritumoral edema provides reliable and quantified objective basis for the differential diagnosis of glioblastoma and solitary metastasis.
7.Effect of detachable fibered coils occlusion system on visceral artery aneurysms
Hongpeng ZHANG ; Wei GUO ; Xiaoping LIU ; Lijun WANG ; Xin JIA ; Jiang XIONG ; Xiaohui MA ; Minhong ZHANG ; Yongle XU
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2018;20(5):454-457
Objective To study the safety and efficacy of detachable fibered coils occlusion system for visceral artery aneurysms.Methods Thirty-three visceral artery aneurysms patients (12 males and 21 females) with an average age of 63.8±3.5 years who underwent endovascular embolization with detachable fibered coils occlusion system combined with standard pushable coils in our hospital were included in this study.Of these patients,20 (60.6%),7 (21.2%),3 (9.1%),2 (6.1 %),and 1 (3.0%) were respectively diagnosed with splenic artery aneurysm,renal aneurysm,superior mesenteric aneurysm,celiac aneurysm,and pancreaticoduodenal aneurysm.The mean diameter of aneurysms was 16-38 (24.0±3.4)mm.The success rate of detachable fibered coils occlusion system for visceral artery aneurysms,postoperative complications and surgical procedure time were recorded.The patients received CT or ultrasonographic follow up at months 3,6,12 and every year after operation.Results The success rate of detachable fibered coils occlusion system for visceral artery aneurysms was 100%.No intraoperative bleeding and coil migration occurred.One patient with splenic artery dissection did not undergo operation.The patients were followed up for 2-24 (12.5±2.3) months,during which no enlargement or rupture of visceral artery aneurysms and no operation-related severe complication or death occurred.Conclusion Detachable fibered coils occlusion system combined with standard pushable coils is safe and effective for mild and moderate visceral artery aneurysms.
8.A Study on the Disaster Medical Response during the Mauna Ocean Resort Gymnasium Collapse.
Myeong il CHA ; Gi Woon KIM ; Chu Hyun KIM ; Minhong CHOA ; Dai Hai CHOI ; Inbyung KIM ; Soon Joo WANG ; In Sool YOO ; Han Deok YOON ; Kang Hyun LEE ; Suck Ju CHO ; Tag HEO ; Eun Seog HONG
Journal of the Korean Society of Emergency Medicine 2017;28(1):97-108
PURPOSE: To investigate and document a disaster medical response during the collapse of the Gyeongju Mauna Ocean Resort gymnasium, which occurred on February 17, 2014. METHODS: The official records of each institution were verified to select the study population. All the medical records and emergency medical service records were reviewed by an emergency physician. Personal or telephonic interviews were conducted without a separate questionnaire if the institutions or agencies crucial to disaster response did not have official records or if information from different institutions was inconsistent. RESULTS: One hundred fifty-five accident victims, who were treated at 12 hospitals mostly for minor wounds, were included in this study. The collapse killed 10 people. Although the news of the collapse was disseminated in 4 minutes, it took at lease 69 minutes for a dispatch of 4 disaster medical assistance teams to take action; 4.5% of patients were treated on-site, 56.7% were transferred to 2 nearest hospitals, and 42.6% were transferred to hospitals with poor preparation to handle disaster victims. CONCLUSION: In the collapse of the Gyeongju Mauna Ocean Resort gymnasium, the initial triage and distribution of patients were inefficient, with delayed arrival of medical assistance teams. These problems had also been noted in prior mass casualty incidents. Government agencies are implementing improvements, and this study could aid the implementation process.
Disaster Victims
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Disasters*
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Emergencies
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Emergency Medical Services
;
Government Agencies
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Gyeongsangbuk-do
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Health Resorts*
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Humans
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Mass Casualty Incidents
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Medical Assistance
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Medical Records
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Social Networking
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Triage
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Wounds and Injuries
9.MR texture analysis in differential diagnosis of glioblastoma and solitary metastatic brain tumor
Chinese Journal of Medical Imaging Technology 2017;33(12):1784-1787
Objective To explore the value of MR texture analysis in differential diagnosis of glioblastoma and solitary metastasis.Methods Thirty-five patients with brain glioblastomas and forty patients with brain metastases confirmed by pathology or clinic were enrolled.All patients underwent conventional MR scan and enhanced examination,including T1 FLAIR,T2WI,T2 FLAIR,DWI,and enhanced T1WI.Texture features of the lesions were extracted with MaZda software by manually drawing ROI on the maximum level of tumor delineation in DWI and enhanced T1WI.Results There were statistical differences between glioblastoma and solitary metastasis of enhanced T1WI skewness in the histogram class texture parameters,gray co-occurrence matrix parameters including enhanced T1WI image correlation,mean and DWI correlation.Logistic regression analysis showed the area under ROC curve of the model was 0.834.Conclusion Texture analysis can provide reliable and quantified objective basis for differential diagnosis of glioblastoma and solitary metastatic brain tumor.
10.Intraperitoneal injection of bleomycin induces pulmonary fibrosis in mice:a long-term stability evaluation
Minhong SU ; Ning JIANG ; Hongtao LI ; Zhenguo WANG ; Yufen XIE ; Xiaobin ZHENG ; Changli TU ; Jin HUANG
Chinese Journal of Tissue Engineering Research 2017;21(4):512-519
BACKGROUND:There is no effective drug for idiopathic pulmonary fibrosis (IPF), because of a lack of the animal model imitating the complete pathogenesis of human IPF. Therefore, it is critical to establish an ideal animal IPF model used for investigating the underlying pathogenesis and developing a kind of effective drug. OBJECTIVE:To establish an animal model that can mimic more characters of human IPF. METHODS:Seventy male C57BL/6 mice were randomly divided into two groups, fol owed by subjected to the intraperitoneal injection of bleomycin (35 mg/kg) on days 1, 4, 8, 11, 15, 18, 22, and 25, twice (group A) or once (group B) a week. Mice were sacrificed at 2, 4, 6, 8, and 10 weeks after the eighth injection, and the lung tissues were moved used for hematoxylin-eosin, Masson and immunohistochemical stainings. RESULTS AND CONCLUSION:There were various degrees of alveolitis and pulmonary fibrosis in the two groups at different time points after the last injection. The scores of alveolitis and pulmonary fibrosis in the group A began to gradual y increase from the 2nd week and reached the highest level at the 6th-8th weeks until the 10th week. In contrast, the scores of alveolitis and pulmonary fibrosis in the group B peaked at the 2nd week, then fluctuately decreased, and were significantly lower than those in the group A at the 6th week (P<0.05). Immunohistochemistry showed that type I col agen deposition was mainly distributed in the subpleural region, peri-vascular region and alveolar septa, which was consistent with Masson staining findings. The expression levels of transforming growth factorβ1 (TGF-β1) andα-smooth muscle actin (α-SMA) in the regions developing alveolitis and pulmonary fibrosis were significantly increased. In the group A, the expression levels of type I col agen, TGF-β1,α-SMA, and the hydroxyproline content in the lung tissues reached the peak level at 6-8 weeks. However, in the group B, al above indicators reached the highest level at the 2nd week, but gradual y decreased thereafter. At the 4th week, the expression Levels of TGF-β1 andα-SMA in the group B were significantly lower than those in the group A (P<0.05). At the 6th week, the hydroxyproline and type I col agen levels in the group B were significantly lower than those in the group A (P<0.05). In conclusion, the mouse model of pulmonary fibrosis induced by intraperitoneal injection of 35 mg/kg bleomycin twice weekly can be used to mimic the repetitive wound healing process, pathological morphology and cytokine changes of human IPF, which is prone to administration, with better stability and repeatability. This model is of great significance for the study on IPF. Subject headings:Disease Models, Animal;Pulmonary Fibrosis;Bleomycin


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