1.The predictive value of very low frequency power for the efficacy of vitamin D treatment in children with postural orthostatic tachycardia syndrome
Tong DONG ; Jin WANG ; Weixia WU ; Yan WANG ; Shaomin NIU ; Xiaojuan YAN ; Li MIN ; Huitao MENG ; Xiangyu DONG
Chinese Journal of Pediatrics 2025;63(10):1115-1120
Objective:To explore the predictive value of very low frequency (VLF) for the efficacy of vitamin D treatment in children with postural orthostatic tachycardia syndrome (POTS).Methods:A retrospective case-control study was conducted. A total of 65 POTS children from the Department of Pediatrics of the Second Hospital of Lanzhou University from November 2023 to May 2024 were selected as the research subjects, while 102 healthy children from the same period were selected as the control group. The 25 (OH) D levels between POTS children and healthy children were compared. The frequency of eight main symptoms, including palpitations, headache, cold sweat, blurred vision, chest tightness, dizziness, fainting, and digestive discomfort in the POTS group were analyzed, the symptom scores of the orthostatic intolerance were calculated, and the parameters related to short-range heart rate variability (HRV) during the upright test, head-up tilt test (HUTT) were collected. The correlation between 25 (OH) D levels and symptom scores of orthostatic intolerance symptoms and HRV parameters in children with POTS were analyzed by Pearson correlation analysis. The total symptom scores of children with POTS were compared for 3 months before treatment and 2 months after treatment with vitamin D 800 U/d. The difference in score before and after treatment was ≥2 as responsive group, and the score difference before and after treatment was <2 as non-responsive group. The demographic characteristics including age, gender, height, weight, body mass index, as well as HRV parameters such as the standard deviation of nn intervals (SDNN), the standard deviation of the average NN intervals (SDANN), the root mean square of successive differences (rMSSD), low-frequency (LF), high-frequency (HF), very-low-frequency (VLF) were compared between the responsive group and non-responsive group. Multivariate Logistic regression was analyzed to screen independent influencing factors of vitamin D treatment efficacy for POTS. The marker molecules related to the efficacy of vitamin D treatment in children with POTS were analyzed through receiver operating characteristic (ROC) curve.Results:A total of 167 children were included in this study. There were 65 children in the POTS group, 38 males and 27 females, with the age of (10.6±2.2) years. There were 102 healthy children in the control group, 53 males and 49 females, with the age of (11.2±1.8) years.There was no statistically significant difference in gender and age between the two groups (both P>0.05). The serum 25 (OH) D level in children in the POTS group was (37±18)nmol/L, lower than that in the control group (61±17)nmol/L ( P<0.05).Pearson correlation analysis showed that serum 25(OH)D was positively correlated with VLF, SDNN and HF ( r=0.43, 0.65, 0.36, respectively, all P<0.05). Among the POTS children, there were 48 cases in responsive group and 17 cases in non-responsive group. Univariate analysis revealed that responsive group exhibited significantly lower values in age, SDNN, SDANN, and VLF compared to the non-responsive group (all P<0.05). Multivariate Logistic regression analysis showed that age ( OR=1.47, 95% CI 1.08-2.01), SDNN ( OR=1.01, 95% CI 1.00-1.22) and VLF ( OR=1.01, 95% CI 1.00-1.15) were independent influencing factors in the effect of vitamin D in POTS children (all P<0.05). ROC curve analysis showed that the area under the curve of VLF predicting response to vitamin D treatment for POTS was 0.72 (95% CI 0.58-0.85, P=0.008). When the cutoff value was 1 272 ms 2, the sensitivity and specificity were both 70%. Conclusion:VLF may help predict the efficacy of vitamin D treatment in children with POTS.
2.Clinical features and prognosis of patients with primary sclerosing cholangitis:An analysis of 107 cases
Tongtong MENG ; Weijia DUAN ; Xinyu LI ; Junqi NIU ; Huiguo DING ; Ying HAN ; Wen XIE ; Lu ZHOU ; Bangmao WANG ; Liping GUO ; Jie LI ; Bei JIA ; Lingyi ZHANG ; Liang WANG ; Xiaoqian XU ; Yu WANG ; Xiaojuan OU ; Xinyan ZHAO ; Hong YOU ; Jidong JIA ; Yuanyuan KONG
Journal of Clinical Hepatology 2025;41(7):1337-1343
Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.
3.Clinical features and prognosis of patients with primary sclerosing cholangitis:An analysis of 107 cases
Tongtong MENG ; Weijia DUAN ; Xinyu LI ; Junqi NIU ; Huiguo DING ; Ying HAN ; Wen XIE ; Lu ZHOU ; Bangmao WANG ; Liping GUO ; Jie LI ; Bei JIA ; Lingyi ZHANG ; Liang WANG ; Xiaoqian XU ; Yu WANG ; Xiaojuan OU ; Xinyan ZHAO ; Hong YOU ; Jidong JIA ; Yuanyuan KONG
Journal of Clinical Hepatology 2025;41(7):1337-1343
Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.
4.The predictive value of very low frequency power for the efficacy of vitamin D treatment in children with postural orthostatic tachycardia syndrome
Tong DONG ; Jin WANG ; Weixia WU ; Yan WANG ; Shaomin NIU ; Xiaojuan YAN ; Li MIN ; Huitao MENG ; Xiangyu DONG
Chinese Journal of Pediatrics 2025;63(10):1115-1120
Objective:To explore the predictive value of very low frequency (VLF) for the efficacy of vitamin D treatment in children with postural orthostatic tachycardia syndrome (POTS).Methods:A retrospective case-control study was conducted. A total of 65 POTS children from the Department of Pediatrics of the Second Hospital of Lanzhou University from November 2023 to May 2024 were selected as the research subjects, while 102 healthy children from the same period were selected as the control group. The 25 (OH) D levels between POTS children and healthy children were compared. The frequency of eight main symptoms, including palpitations, headache, cold sweat, blurred vision, chest tightness, dizziness, fainting, and digestive discomfort in the POTS group were analyzed, the symptom scores of the orthostatic intolerance were calculated, and the parameters related to short-range heart rate variability (HRV) during the upright test, head-up tilt test (HUTT) were collected. The correlation between 25 (OH) D levels and symptom scores of orthostatic intolerance symptoms and HRV parameters in children with POTS were analyzed by Pearson correlation analysis. The total symptom scores of children with POTS were compared for 3 months before treatment and 2 months after treatment with vitamin D 800 U/d. The difference in score before and after treatment was ≥2 as responsive group, and the score difference before and after treatment was <2 as non-responsive group. The demographic characteristics including age, gender, height, weight, body mass index, as well as HRV parameters such as the standard deviation of nn intervals (SDNN), the standard deviation of the average NN intervals (SDANN), the root mean square of successive differences (rMSSD), low-frequency (LF), high-frequency (HF), very-low-frequency (VLF) were compared between the responsive group and non-responsive group. Multivariate Logistic regression was analyzed to screen independent influencing factors of vitamin D treatment efficacy for POTS. The marker molecules related to the efficacy of vitamin D treatment in children with POTS were analyzed through receiver operating characteristic (ROC) curve.Results:A total of 167 children were included in this study. There were 65 children in the POTS group, 38 males and 27 females, with the age of (10.6±2.2) years. There were 102 healthy children in the control group, 53 males and 49 females, with the age of (11.2±1.8) years.There was no statistically significant difference in gender and age between the two groups (both P>0.05). The serum 25 (OH) D level in children in the POTS group was (37±18)nmol/L, lower than that in the control group (61±17)nmol/L ( P<0.05).Pearson correlation analysis showed that serum 25(OH)D was positively correlated with VLF, SDNN and HF ( r=0.43, 0.65, 0.36, respectively, all P<0.05). Among the POTS children, there were 48 cases in responsive group and 17 cases in non-responsive group. Univariate analysis revealed that responsive group exhibited significantly lower values in age, SDNN, SDANN, and VLF compared to the non-responsive group (all P<0.05). Multivariate Logistic regression analysis showed that age ( OR=1.47, 95% CI 1.08-2.01), SDNN ( OR=1.01, 95% CI 1.00-1.22) and VLF ( OR=1.01, 95% CI 1.00-1.15) were independent influencing factors in the effect of vitamin D in POTS children (all P<0.05). ROC curve analysis showed that the area under the curve of VLF predicting response to vitamin D treatment for POTS was 0.72 (95% CI 0.58-0.85, P=0.008). When the cutoff value was 1 272 ms 2, the sensitivity and specificity were both 70%. Conclusion:VLF may help predict the efficacy of vitamin D treatment in children with POTS.
5.Study of spiral CT 3D scanning reconstruction combined with 3D printing in acetabular fracture surgery
Shanshan WANG ; Junqiao NIU ; Jia WANG ; Xiaojuan LI ; Yue HONG ; Li WANG
China Medical Equipment 2024;21(5):59-63
Objective:To explore the clinical application value of spiral computed tomography(CT)three-dimensional(3D)scanning reconstruction combined with 3D printing technique in surgery for acetabular fracture.Methods:A total of 71 patients with acetabular fractures admitted to Xinjiang Uiger Municipal People's Hospital from January 2018 to December 2020,who underwent surgical treatment,were selected as the research objects.According to different treatment methods,they were divided into observation group(38 cases)and control group(33 cases).The observation group adopted spiral CT 3D reconstruction,and 3D printing was used to assist the treatment of internal fixation,and the control group adopted conventionally surgical treatment.And then,the surgical effect and recovery situation of the two groups were compared.Results:The quality score(Malta)of fracture reduction and the hip score of sub-item percentile of observation group were significantly higher than those of the control group,and the intraoperative blood loss,the times of intraoperative fluoroscopy,the operation time and hospitalization time of observation group were significantly lower than those of control group(t=23.426,4.216,3.425,17.783,P<0.05),respectively.There was significant difference in the excellent rate of fracture reduction between two groups(x2=4.059,P<0.05).The pain,function and joint activity scores of hip joint function scores of patients in observation group were significantly higher than those of control group(t=-4.873,-5.776,-6.247,P<0.05),respectively.The incidence of complications in observation group was significantly lower than that in control group(x2=4.059,P<0.05).Conclusion:In the perioperative period,the application of spiral CT 3D reconstruction combined with 3D printing of acetabular fractures can further ensure the safety and feasibility of the operation,and improve the quality and efficiency of the surgery,and promote postoperative recovery.
6.High-throughput screening of novel TFEB agonists in protecting against acetaminophen-induced liver injury in mice.
Xiaojuan CHAO ; Mengwei NIU ; Shaogui WANG ; Xiaowen MA ; Xiao YANG ; Hua SUN ; Xujia HU ; Hua WANG ; Li ZHANG ; Ruili HUANG ; Menghang XIA ; Andrea BALLABIO ; Hartmut JAESCHKE ; Hong-Min NI ; Wen-Xing DING
Acta Pharmaceutica Sinica B 2024;14(1):190-206
Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.
7.Imaging characteristics of CT angiography of the aorta in active Takayasu arteritis
Jia WANG ; Junqiao NIU ; Xiaojuan LI ; Yan LIU
Chinese Journal of Rheumatology 2023;27(12):806-813
Objective:To explore the imaging characteristics and clinical value of CT angiography (CTA) of the aorta in active arteritis.Methods:A retrospective analysis was conducted on the clinical data and laboratory examination results of 77 patients with Takayasu arteritis (TAK) admitted to the Rheumatology and Immunology Department of People′s Hospital of Xinjiang Uygur Autonomous Region from January 2015 to October 2022. They were divided into two groups: 62 cases in the TAK active group and 15 cases in the TAK inactive group. Among them, 17 patients were followed up, 13 cases became inactive, and 4 cases remained active. A total of 94 aortic CTA imaging results were divided into 2 groups, with 66 cases in the TAK active group and 28 cases in the TAK inactive group.All patients underwent plain chest and abdominal CT scans, aortic CTA, and post-processing examinations, with 12 active TAK patients undergoing delayed aortic enhancement scans. The t-test, Mann Whitney U test, χ2 Testing, Fisher′s exact probability method and Pearson/Spearman correlation analysis were used for data analysis. The imaging features of the two groups were measured and compared, the correlation between imaging features and laboratory results, Kerr score were investigated. The diagnositic efficacy of imaging features were explored and imaging features before and after treatment were analyzed. Results:In the TAK active and inactive groups, course of disease[14 (1, 29) months vs 33(8, 69)months, Z=2.70, P=0.007], Physical malaise or weight loss[32.3%(20/62) vs 20.0%(3/15), χ2=4.08, P=0.043], increased ESR [98.4% (61/62) vs 13.3% (2/15)], χ2=64.69, P<0.001], CRP level[69.4% (43/62) vs 6.7%(1/15), χ2=29.94, P<0.001] were statistically significant. The vascular wall thickness of the two groups was significantly different [(4.2±1.4)mm vs (2.4±0.8)mm, t=7.81, P<0.001], CT mean value of the garterial wall [(81±8) Hu vs (70±13)Hu, t=2.82, P=0.011], CT max value of the arterial wall [(106±12)Hu vs (96±12)Hu, t=2.38, P=0.024], relative CT value 1 of the arterial wall (0.20±0.08 vs 0.14±0.04, t=2.56, P=0.016), relative CT value 2 of the arterial wall (1.23±0.18 vs 1.06±0.17, t=2.63, P=0.013), CT mean value of periaortic adipose tissue [(-31±12)Hu vs (-58±20)Hu, t=4.80, P<0.001)], CT max value of periaortic adipose tissue [-35(-45,-25)Hu vs -87(-95, -42)Hu, Z=4.27, P<0.001], CT mean value of adipose tissue around branches[-28(-33, -14)Hu vs -76(-83, -31)Hu, Z=3.37, P=0.001], CT max value of adipose tissue around branches[-7(-13,-1)Hu vs -59(-72, -14)Hu, Z=3.74, P<0.001], relative CT values of adipose tissue around the aorta (0.26 ± 0.09 vs 0.51 ± 0.19, t=4.47, P<0.001)], relative CT values of adipose tissue around branches (0.17 ± 0.09 vs 0.28 ± 0.18, t=2.35, P=0.025) were significant different. The wall thickness value, relative CT value of periaortic adipose tissue, and CT mean value of periaortic adipose tissue had high diagnostic efficacy, with cut-off values of 3.25 mm, 0.455, and -55 Hu, respectively. The AUCs were 0.911, 0.887, and 0.863, respectively. The Youden index was 0.687, 0.730, and 0.715, respectively. The sensitivity and specificity were 0.758 and 0.929, 0.909 and 0.821, 0.894 and 0.821, respectively. After treatment, 11 active TAK patients became inactive, with reduced wall thickening, enhancement, and density of perivascular adipose tissue. Thirteen patients with active TAK underwent delayed aortic enhancement scanning, and it was found that the low-density loop sign of the aortic intima was more clearly displayed during this period, and the enhancement amplitude of the vascular wall tended to be uniform. Conclusion:Aortic CTA is an effective method for qualitative evaluation of TAK activity.
8.Research Progress of Digestive System Disease and Syndrome Combined Animal Model and Traditional Chinese Medicine Target Intervention: A Review
Wenjuan XU ; Longde WANG ; Yuanyuan NIU ; Lanfang MAO ; Xiaojuan DU ; Ping ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(19):258-266
Reflux esophagitis (liver-stomach disharmony, Spittoon-Qi interties, Qi and blood stasis syndrome, turbid poison intrinsic) and nonalcoholic fatty liver disease (liver depression, spleen deficiency, phlegm and blood stasis syndrome, hot and humid embodiment, phlegmy wet resistance) and functional dyspepsia (liver depression syndrome, liver stomach with spleen deficient, spleen deficiency cold syndrome, in a word, fever) is a common disease and frequently encountered disease of digestive system. The course of disease is prolonged and the prevalence is high. The successful establishment of animal model combining disease and syndrome is the premise of exploring the mechanism of traditional Chinese medicine(TCM) effect and the foundation of the development of new preparations. At the same time, mastering the complex relationship network among disease, syndrome and prescription is the prerequisite of effective treatment. When the same syndrome occurs between different diseases, the concept of "treating different diseases with the same treatment" in TCM suggests that methods can be cross-referenced for the shortage of some syndrome models. TCM intervention of digestive diseases has the characteristics of multi-path, multi-target, multi-dimension and multi-level. Therefore, this article through the literature review, summarizes the reflux esophagitis, nonalcoholic fatty liver disease and functional dyspepsia is a common disease such as the combined operation method of the model and the intervention mechanism of TCM, so as to diseases of the digestive system of different syndrome types provides the theory basis for the objective of research, and the basic research of TCM prescription and achievements provide methodological guidance.
9.Efficacy Differences of First-line EGFR-TKIs Alone vs in Combination with Chemotherapy in Advanced Lung Adenocarcinoma Patients with Sensitive EGFR Mutation and Concomitant Non-EGFR Genetic Alterations.
Guowei ZHANG ; Ruirui CHENG ; Yuanyuan NIU ; Huijuan WANG ; Xiangtao YAN ; Mina ZHANG ; Xiaojuan ZHANG ; Jinpo YANG ; Chunhua WEI ; Zhiyong MA
Chinese Journal of Lung Cancer 2022;25(9):651-657
BACKGROUND:
Epidermal growth factor receptor (EGFR) mutations are often associated with non-EGFR genetic alterations, which may be a reason for the poor efficacy of EGFR tyrosine kinase inhibitors (TKIs). Here we conducted this study to explore whether EGFR-TKIs combined with chemotherapy would benefit advanced lung adenocarcinoma patients with both sensitive EGFR mutation and concomitant non-EGFR genetic alterations.
METHODS:
Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant non-EGFR genetic alterations were retrospectively collected. And the patients were required to receive first-line EGFR-TKIs and chemotherapy combination or EGFR-TKIs monotherapy. Demographic, clinical and pathological data were collected, and the electronic imaging data were retrieved to evaluate the efficacy and time of disease progression. Survival data were obtained through face-to-face or telephone follow-up. The differences between the two groups in objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were investigated.
RESULTS
107 patients were included, including 63 cases in the combination group and 44 cases in the monotherapy group. The ORR were 78% and 50% (P=0.003), and DCR were 97% and 77% (P=0.002), respectively. At a median follow-up of 13.7 mon, a PFS event occurred in 38.1% and 81.8% of patients in the two groups, with median PFS of 18.8 mon and 5.3 mon, respectively (P<0.000,1). Median OS was unreached in the combination group, and 27.8 mon in the monotherapy group (P=0.31). According to the Cox multivariate regression analysis, combination therapy was an independent prognostic factor of PFS CONCLUSIONS: In patients with EGFR-mutant advanced lung adenocarcinoma with concomitant non-EGFR genetic alterations, combination of TKIs and chemotherapy was significantly superior to EGFR-TKIs monotherapy, which should be the preferred treatment option.
Adenocarcinoma of Lung/genetics*
;
ErbB Receptors/genetics*
;
Humans
;
Lung Neoplasms/pathology*
;
Mutation
;
Protein Kinase Inhibitors/therapeutic use*
;
Retrospective Studies
10.Interleukin-1β mediates the effect of macrophage androgen receptor on hyperphosphate-induced vascular smooth muscle cell calcification
Haiyan PANG ; Zhi LU ; Longfei XIAO ; Haiyan CHEN ; Zhiqun SHANG ; Ning JIANG ; Xiaojuan WANG ; Fang WEI ; Aili JIANG ; Lin WANG ; Yuanjie NIU
Chinese Journal of Nephrology 2022;38(5):420-427
Objective:To investigate whether it is by regulating interleukin 1β ( IL-1β) gene expression that androgen receptor (AR) in macrophages affects hyperphosphate-induced vascular smooth muscle cell calcification. Methods:The chromatin immunoprecipitation (ChIP) experiment was used to determine whether AR was bound to the androgen receptor element (ARE) sequence of IL-1β promoter in THP-1 cells. Whether the AR regulated IL-1β gene expression was detected by luciferase assay experiments. AR of THP-1 cells was silenced and transfected by lentivirus with vector or shRNA. Flow cytometry was used to select positive transfected cells THP-1ARsc (control) and THP-1ARsi (AR silencing) with fluorescent markers. Western blotting was used to detect AR protein levels of THP-1ARsc (control) and THP-1ARsi cells (AR silencing in monocytes). Macrophages MФARsc (control) or MФARsi (AR silencing) were induced by 50 ng/ml phorbol ester. Enzyme-linked immunosorbent assay was used to detect IL-1β expression levels of MФARsc or MФARsi conditioned medium. The human aortic smooth muscle cells (HASMC) were cultured in MФARsc or MФARsi conditioned medium with phosphate (2.5 mmol/L final concentration of sodium dihydrogen phosphate), and Alizarin red S staining was used to analyze HASMC calcification degree. Western blotting was used to detect the expression levels of RUNX2 (osteoblast marker) and SM22α (HASMC marker), and neutralization assay was performed to test IL-1β-mediating effect of macrophages AR on HASMC calcification. Results:AR was bound to ARE sequence of IL-1β promoter and regulated IL-1β gene expression. The expression level of IL-1β protein in conditioned medium of MФARsi cells decreased significantly compared to MФARsc cells ( P<0.001). Compared with MФARsc conditioned medium group, HASMC calcium deposition in MФARsi conditioned medium group decreased significantly, RUNX2 protein decreased and SM22α protein increased (all P<0.05). The degree of HASMC calcification in the MФARsi conditioned medium+IgG antibody group decreased than that in the MФARsc conditioned medium+IgG antibody group significantly, and the degree of HASMC calcification in the MФARsc conditioned medium+IL-1β antibody group decreased significantly than that in the MФARsc conditioned medium+IgG antibody group; while the degree of HASMC calcification in the MФARsi conditioned medium+IgG antibody group and MФARsi conditioned medium+IL-1β antibody group decreased than that in the MФARsc conditioned medium+IL-1β antibody group (all P<0.05). Conclusions:Macrophage AR regulates IL-1β expression by binding to ARE sequence within IL-1β promoter, and IL-1β mediates the effect of macrophage AR on hyperphosphate-induced HASMC calcification.

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