1.Salvia miltiorrhiza attenuates white matter injury induced by hypoperfusion in neonatal rats
Xuewen SU ; Haifeng YUAN ; Wanyu FENG ; Ruixia SONG ; Junlong CHEN ; Ruhan YI ; Hua ZHU ; Zhongxia DOU
Chinese Journal of Tissue Engineering Research 2024;28(20):3229-3234
BACKGROUND:Premature birth is a major global health problem associated with high mortality and morbidity.White matter injury is the most common brain injury in preterm infants.Salvia miltiorrhiza is a traditional herbal plant that is commonly used to treat cardiovascular and cerebrovascular diseases in Asian countries. OBJECTIVE:To investigate the therapeutic effect of Salvia miltiorrhiza on white matter injury in preterm infants. METHODS:Eighteen neonatal male Sprague-Dawley rats at 3-day gestational age were selected and randomized into normal group,white matter injury group,and Salvia miltiorrhiza group.Animal models of preterm white matter injury were established by permanent ligation of the right common carotid artery in the latter two groups.Rats in the Salvia miltiorrhiza group were given intraperitoneal injection of Salvia miltiorrhiza(5 mg/kg·d)for 7 consecutive days.Normal group and white matter injury group were given the same volume of PBS for intervention.On the 14th day after modeling,the rats were sacrificed.Brains were pathologically observed by hematoxylin-eosin staining under microscope,and the expression levels of myelin basic protein and CC1 in brain tissue were visualized using immunofluorescence.Furthermore,liquid chromatography-tandem mass spectrometry was used to analyze possible pathways for the action of Salvia miltiorrhiza. RESULTS AND CONCLUSION:In the white matter injury group,the structure of the corpus callosum was irregular and the cells appeared swollen and necrotic.In addition,induction of white matter injury resulted in significantly reduced myelin formation,with irregular and loosely arranged nerve fibers and significantly decreased myelin sheaths.Interestingly,white matter injury rats treated with Salvia miltiorrhiza had reduced cellular swelling,reduced lesions,and increased myelin sheaths.The expression of myelin basic protein was closely related to myelin formation,and CC1 was a marker of myelin oligodendrocytes.Salvia miltiorrhiza significantly up-regulated the expressions of myelin basic protein and CC1 in white matter injury rats(P<0.000 1),indicating that Salvia miltiorrhiza alleviated white matter injury.Liquid chromatography-tandem mass spectrometry analysis showed that the therapeutic effect of Salvia miltiorrhiza in the rat model of white matter injury was closely related to the regulation of complement and coagulation cascades.To conclude,Salvia miltiorrhiza may be a potential therapeutic agent for treating preterm white matter injury.
2.Analysis of diabetes mortality characteristics among the residents in Fengxian District, Shanghai, 2012‒2021
Haifeng XU ; Yi HU ; Zhenyu WU ; Ying CHEN ; Zenan DENG ; Ting XUE ; Yuan YUAN ; Meng QIN ; Haiying TANG
Shanghai Journal of Preventive Medicine 2024;36(11):1060-1064
ObjectiveTo investigate the trends in diabetes mortality rate and the characteristics of decreased population in Fengxian District, Shanghai from 2012 to 2021. MethodsData from the death registration records of the residents in Fengxian District between 2012 and 2021, sourced from the Shanghai Death Surveillance System, were analyzed. Indicators such as the crude mortality rate due to diabetes, the standardized mortality rate, years of life lost (YLL), and the probability of premature death were estimated. Annual percentage change (APC) was used to analyze the temporal trends of mortality and the probability of premature death due to diabetes. Rate decomposition analysis was used to assess the contributions of demographic and non-demographic factors to diabetes mortality. ResultsFrom 2012 to 2021, there were 1 471 deaths due to diabetes in Fengxian District, with a crude mortality rate of 27.51/100 000 and a standardized mortality rate of 17.58/100 000. The crude mortality rate showed an overall increasing trend (APC=4.58%, Z=3.49, P<0.05). The potential years of life lost (PYLL) due to diabetes over this period amounted to 9 715 person-years, with a PYLL rate of 1.82 ‰, and the average years of life lost (AYLL) was 11.94 years. The probability of premature death was 0.41% (APC=3.36%, t=2.33, P<0.05). Both population aging and non-aging factors contributed to the increase in diabetes mortality, with overall contribution rates of 67.99% and 32.01%, respectively. Among men, the contribution rates were 60.57% and 39.43%, while among women, they were 79.43% and 20.57%, respectively. ConclusionFrom 2012 to 2021, both the crude mortality rate and the probability of premature death due to diabetes showed an upward trend among the residents in Fengxian District, with a higher YLL. Population aging was the main factor causing the increase in mortality rate, while non-demographic factors had a greater impact on the rise in diabetes mortality among men than that in women. Therefore, the management on male diabetes patients should be strengthened.
3.Analysis of clinical features of 193 Chinese patients with McCune-Albright syndrome through a literature review
Xin FENG ; Ke YUAN ; Huifei LU ; Haifeng TU ; Jiangfang ZHU ; Yanlan FANG ; Qingfeng YAN ; Chunlin WANG
Chinese Journal of Medical Genetics 2024;41(7):776-782
Objective:To retrospectively analyze the clinical characteristics of 193 Chinese patients with McCune-Albright syndrome (MAS).Methods:By using keywords " McCune-Albright syndrome", " Albright syndrome", or " fibrous dysplasia " as the search terms, 193 cases of MAS reported in China from January 1990 to November 2022 from the Wanfang data, CNKI, VIP, PubMed, and Embase databases were obtained, and their clinical data was retrospectively analyzed. Intergroup comparisons were carried out by using t test, Mann-Whitney U test, and χ2 test. Results:The 193 MAS patients had included 42 males and 151 females, with the median first-visit age of females being younger than males. The typical triad group had accounted for 46.1% of patients, and the middle first-visit and diagnosis age was younger than the atypical group. The primary reason for first-visit in males of MAS was fibrous dysplasia (FD), whilst that in females of MAS was peripheral precocious puberty (PPP). FD has occurred in 84.5% of the patients, with an average age of onset age being 6.1 years old, and 90% was ≤ 16 years of age. Endocrine hyperfunction was found in 79.3% of the patients, with a higher proportion in females compared with males ( P<0.05). Pituitary involvement was seen in 21.8% of the patients, and the incidence of craniofacial FD and cranial nerve compression was significantly higher in those with elevated growth hormone (GH) than without ( P<0.05). Café-au-Lait Spots were noted in 86.5% of the patients, and 28.3% (28/99) had located on the different side of FD. Conclusion:Most MAS patients had atypical manifestations and multi-systemic involvement. It is more common and occurs earlier in females. The most common reasons for initial diagnosis in male and female patients were FD and PPP, respectively. Patients with elevated GH should be examined for cranial nerve compression.
4.A case of successful treatment of an extremely preterm infant born at 21 weeks and 4 days of gestation
Haifeng ZONG ; Bingchun LIN ; Yingsui HUANG ; Shan JIANG ; Yurong YUAN ; Xiaoyun XIONG ; Zhifeng HUANG ; Chuanzhong YANG
Chinese Journal of Perinatal Medicine 2024;27(10):860-864
This case report described the sucussful treatment of a male infant born at 21 weeks and 4 days through assisted reproductive technology. After prenatal consultation and with the strong desire of the parents, active resuscitation and treatment were performed. The infant received 52 days of mechanical ventilation and was extubated to non-invasive ventilation at a corrected gestational age of 28 weeks and 6 days. During hospitalization, no vasoactive drugs were used, and necrotizing enterocolitis did not occur. The gastric tube was removed at a corrected gestational age of 37 weeks and 4 days. At a corrected gestational age of 40 weeks, cranial MRI showed no abnormalities. The infant was discharged at a corrected gestational age of 42 weeks after 143 days of treatment, without the need for any respiratory support. Follow-up until a corrected age of 6 months showed good growth and development.
5.Effect of different strategies on the placement of 5 brands cuffed pediatric tracheal tubes
Yanjun ZHANG ; Hongyin DU ; Sheng WANG ; Jinzhu LIU ; Zhihao YUAN ; Wenjing ZHANG ; Ye ZHANG ; Fei WANG ; Haifeng QIAO ; Zhifen WANG
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2024;31(1):53-57
Objective To investigate the design of cuffed pediatric tracheal tubes and compare the effects of different tracheal intubation depth placement strategies on the position of the tracheal tube tip and cuff of 5 tracheal tube brands.Methods A total of 180 children who were admitted to Tianjin Children's Hospital from October 2020 to December 2021,with endotracheal intubation under general anesthesia,aged 1-6 years,were enrolled.The length of the subglottic airway was measured by electronic bronchoscopy.Dimensional data from 5 cuffed pediatric tracheal tube brands were recorded,including the length of the tracheal tube cuff,the distance from the tip of the tracheal tube to the upper edge of the cuff,and the tip of the tracheal tube to the lower edge of the tube glottis marker line the distance.Calculation of the required cuffed endotracheal tube internal diameter(ID)for 180 pediatric patients was performed based on the Motoyama formula,the positions of tracheal tube tip and upper cuff border were calculated for each of the 180 tracheas using depth mark to based tracheal tube placement,placement of the tracheal tube tip at 2 cm above the carina,and mid-tracheal tube placement.Results There were differences in the dimensional data of the 5 cuffed pediatric tracheal tube brands.Depth mark-based tracheal tube placement resulted in the incidence rate of tube tip to carina placement less than 1 cm was 3.9%-67.8%,and the highest incidence of bronchial intubation is Ruijing,up to 17.8%.The tracheal tube tip was placed 2 cm above the carina,and no improper placement of the tracheal tube cuff and tube tip was found in all brands.Mid-tracheal tube placement led to 100%subglottic and supraglottic tracheal tube cuff positions,except Weili.Conclusions There are differences in design between different brands of cuffed pediatric tracheal tube,and some of the design deficiencies may lead to the risk of airway complications.The method used to guide the insertion depth and the brand of cuffed tracheal tubes can affect the tracheal tube position.Placement of the tracheal tube tip at 2 cm above the carina allowed safe tracheal tube placement in children aged 1-6 years.
6.Comparisons of mesangial C3 deposition and prognosis in IgA nephropathy patients with different rs6677604 single nucleotide polymorphisms
Yanfang NIE ; Haifeng YU ; Xiaoqing WAN ; Yuan CHEN
Chinese Journal of Primary Medicine and Pharmacy 2024;31(11):1644-1649
Objective:To correlate rs6677604 single nucleotide polymorphism (SNP) with mesangial C3 deposition and prognosis among patients with IgA nephropathy.Methods:A retrospective nested case-control study was conducted among 380 patients with IgA nephropathy who received treatment at Taizhou Central Hospital from July 2018 to July 2021. All patients were tested for rs6677604 SNP. Among them, 36 AG genotypes and 72 GG genotypes were selected. The clinical data (IgA, C4, C3 deposit scores, percutaneous kidney biopsy, interstitial fibrosis/glomerular atrophy, mesangial C3 deposition), tissue and circulating complement levels, and CFHR gene copy numbers were compared between two genotypes. Regular follow-ups were conducted for 2 years to analyze the prognosis of patients with different rs6677604 genotypes. Results:Patients with the rs6677604-AG genotype had scores of (1.34 ± 0.50) points for IgA, (1.47 ± 0.31) points for C4 deposit, and (2.65 ± 0.36) points for C3 deposit, all of which were significantly lower than those in patients with rs6677604-GG genotype [(1.77 ± 0.73) points, (2.17 ± 0.33) points, (3.00 ± 0.48) points, t = -3.17, -10.59, -3.86, all P < 0.05]. The deposition intensity of mesangial C3 was predominantly 2+. Circulating levels of C3, C4, and complement factor H were significantly higher in patients with rs6677604-AG genotype compared with patients with rs6677604-GG genotype ( t = 7.90, 9.87, 2.27, all P < 0.05). Circulating levels of IgA and Gd-IgA1 were significantly lower in patients with rs6677604-AG genotype compared with those with rs6677604-GG genotype ( t = -2.98, -2.08, both P < 0.05). All patients with rs6677604-AG genotype had 1 copy of the CFHR3 gene, with 33 cases (91.67%) having 1 copy and 3 cases (8.33%) having 2 copies of the CFHR1 gene. Both CFHR3 and CFHR1 genes in patients with rs6677604-GG genotype were 2 copies. There was no statistically significant difference in composite endpoint between patients with rs6677604-AG and rs6677604-GG genotypes over the 2-year period (χ 2 = 0.19, P = 0.656). Conclusion:RS6677604 SNP is correlated with circulating complement factor H levels and mesangial C3 deposition in patients with IgA nephropathy, and may have a regulatory effect on complement activation in IgA nephropathy.
7.Aprospective study of detection and clinical significance of bone marrow tumor cells in small cell lung cancer
Ying WANG ; Baohua LU ; Yuan GAO ; Yanxia LIU ; Mingming HU ; Nanying CHE ; Haifeng LIN ; Hongxia LI ; Hongmei ZHANG ; Tongmei ZHANG
Chinese Journal of Oncology 2024;46(5):419-427
Objective:To investigate the detection of bone marrow tumor cells in small cell lung cancer (SCLC) patients and their relationship with clinical features, treatment response and prognosis.Methods:A total of 113patients with newly diagnosed SCLC from January 2018 to October 2022 at Beijing Chest Hospital were prospectively enrolled. Before treatment, bone marrow was aspirated and separately submitted for tumor cells detection by liquid-based cytology and disseminated tumor cells (DTCs) detection by the substrction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) platform. The correlation between the detection results of the two methods with patients' clinical features and treatment response was evaluated by Chi-square. Kaplan-Meier method was applied to create survival curves and the Cox regression model was used for multivariate analysis.Results:The positive rate of bone marrow liquid-based cytology in SCLC was 15.93% (18/113). The liver and bone metastases rates were significantly higher (55.56% vs 11.58% for liver metastasis, P<0.001; 77.78% vs 16.84% for bone metastasis, P<0.001) and thrombocytopenia was more common (16.67% vs 2.11%, P=0.033) in patients with tumor cells detected in liquid-based cytology than those without detected tumor cells. As for SE-iFISH, DTCs were detected in 92.92% of patients (105/113), the liver and bone metastasis rates were significantly higher (37.93% vs 11.90% for liver metastasis, P=0.002; 44.83% vs 20.23 % for bone metastasis, P=0.010), and the incidence of thrombocytopenia was significantly increased (13.79% vs 1.19%, P=0.020) in patients with DTCs≥111 per 3 ml than those with DTCs<111 per 3 ml. The positive rates of bone marrow liquid-based cytology in the disease control group and the disease progression group were 12.00% (12/100) and 46.15% (6/13), respectively, and the difference was statistically significant ( P=0.002). However, the result of SE-iFISH revealed the DTCs quantities of the above two groups were 29 (8,110) and 64 (15,257) per 3 ml, and there was no statistical difference between the two groups ( P=0.329). Univariate analysis depicted that the median progression-free survival (PFS) and median overall survival (OS) of liquid-based cytology positive patients were significantly shorter than those of tumor cell negative patients (6.33 months vs 9.27 months for PFS, P=0.019; 8.03 months vs 19.50 months for OS, P=0.019, P=0.033). The median PFS and median OS in patients with DTCs≥111 per 3 ml decreased significantly than those with DTCs<111 per 3 ml (6.83 months vs 9.50 months for PFS, P=0.004; 11.2 months vs 20.60 months for OS, P=0.019). Multivariate analysis showed that disease stage ( HR=2.806, 95% CI:1.499-5.251, P=0.001) and DTCs quantity detected by SE-iFISH ( HR=1.841, 95% CI:1.095-3.095, P=0.021) were independent factors of PFS, while disease stage was the independent factor of OS ( HR=2.538, 95% CI:1.169-5.512, P=0.019). Conclusions:Both bone marrow liquid-based cytology and SE-iFISH are clinically feasible. The positive detection of liquid-based cytology or DTCs≥111 per 3 ml was correlated with distant metastasis, and DTCs≥111 per 3 ml was an independent prognostic factor of decreased PFS in SCLC.
8.Association between body composition and coronary artery calcification in patients with chronic kidney disease
Jiajin HAN ; Jingwei GAO ; Zhenjian XU ; Zhimin YUAN ; Ying TANG ; Haifeng ZHANG ; Yangxin CHEN ; Jingfeng WANG ; Pinming LIU
Chinese Journal of Cardiology 2024;52(6):676-683
Objective:To investigate the association between body composition and coronary artery calcification in patients with chronic kidney disease (CKD).Methods:This cross-sectional study enrolled patients with CKD hospitalized from May 2019 to April 2022 at Sun Yat-sen Memorial Hospital, Guangzhou, China. Skeletal muscle mass index and visceral fat area were measured by bioelectrical impedance analysis. Coronary artery calcification was assessed by computed tomography. Patients were divided into coronary artery calcification group and non-coronary artery calcification group according to the incidence of coronary artery calcification. Patients were categorized into tertile groups according to their skeletal muscle mass index and visceral fat area levels ranging from the lowest to the highest levels (T1 to T3). We defined skeletal muscle mass index≤30.4% as low muscle mass and visceral fat area≥80.6 cm 2 as high visceral fat based on the results of the restricted cubic spline graph. All individuals were divided into 4 phenotypes: normal body composition, low muscle mass, high visceral fat, and low muscle mass with high visceral fat. Spearman correlation analysis and logistic regression analysis were used to assess the association between skeletal muscle mass index, visceral fat area and coronary artery calcification. Results:A total of 107 patients with CKD were enrolled, with an age of (60.0±14.1) years, including 41 female patients (38.3%). Patients of coronary artery calcification group had lower skeletal muscle mass index ((32.0±4.8) vs. (34.3±4.8), P=0.016) and higher visceral fat area ((70.8±32.6) cm 2 vs. (47.9±23.8) cm 2, P<0.001) than those of non-coronary artery calcification group. Patients in the T3 group of skeletal muscle mass index had a lower prevalence of coronary artery calcification (17 (48.6%) vs. 28 (77.8%)) and a lower coronary artery calcification score (0.5 (0, 124.0) vs. 12.0 (0.3, 131.0)) than those in the T1 group ( P<0.05). Similarly, patients in the T1 group of visceral fat area had a lower prevalence of coronary artery calcification (14 (40.0%) vs. 29 (80.6%)) and a lower coronary artery calcification score (0 (0, 3.0) vs. 37.0 (2.0, 131.0)) than those in the T3 group ( P<0.05). Likewise, patients with both low muscle mass and low muscle mass with high visceral fat had a higher prevalence of coronary artery calcification (11(78.6%) vs. 33 (47.8%); 15 (83.3%) vs. 33 (47.8%)) and a higher coronary artery calcification score (31.1 (0.8, 175.8) vs. 0 (0, 16.4); 27.6 (6.4, 211.4) vs. 0 (0, 16.4)) than those with normal body composition ( P<0.05). Spearman correlation analysis showed that skeletal muscle mass index was inversely correlated with coronary artery calcification score ( r=-0.212, P=0.028), and visceral fat area was positively correlated with coronary artery calcification score ( r=0.408, P<0.001). Multivariate logistic regression analysis showed that increased skeletal muscle mass index was inversely associated with coronary artery calcification prevalence (T2: OR=0.208, 95% CI: 0.056-0.770, P=0.019; T3: OR=0.195, 95% CI: 0.043-0.887, P=0.034), and reduced visceral fat area was inversely associated with coronary artery calcification prevalence (T1: OR=0.256, 95% CI: 0.071-0.923, P=0.037; T2: OR=0.263, 95% CI: 0.078-0.888, P=0.031). Consistently, both low muscle mass and low muscle mass with high visceral fat were associated with coronary artery calcification prevalence ( OR=6.616, 95% CI: 1.383-31.656, P=0.018; OR=5.548, 95% CI: 1.062-28.973, P=0.042). Conclusion:Reduced skeletal muscle mass index and increased visceral fat area are significantly associated with both the prevalence and severity of coronary artery calcification in patients with CKD.
9.Prognosis of different hemodynamic classifications in patients with pulmonary hypertension due to left heart disease
Yuan TANG ; Yanping SHI ; Lu CHEN ; Yifang SUO ; Shengen LIAO ; Cheang LOKFAI ; Yanli ZHOU ; Rongrong GAO ; Jing SHI ; Wei SUN ; Hao ZHANG ; Yanhui SHENG ; Rong YANG ; Xiangqing KONG ; Xinli LI ; Haifeng ZHANG
Chinese Journal of Cardiology 2024;52(10):1177-1185
Objective:To compare the prognostic values of different classification by using transpulmonary pressure gradient (TPG), diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) in patients with pulmonary hypertension due to left heart disease (PH-LHD), and investigated hemodynamic and clinical factors associated with mortality in patients with PH-LHD.Methods:This was a single-center prospective cohort study. In-hospital patients diagnosed with PH-LHD via right heart catheterization at the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, from September 2013 to December 2019 were enrolled. Patients were divided according to TPG (cutoff value 12 mmHg; 1 mmHg=0.133 kPa), DPG (cutoff value 7 mmHg), PVR (cutoff value 3 Wood Units), and the combination of TPG and PVR. Baseline characteristic was recorded. All patients were followed up until the occurrence of endpoint event, defined as all-cause death that occurred during the follow-up period, or until April 18, 2022. Receiver operating characteristic curves were used to compare the predictive value of 3 classification methods for all-cause death in PH-LHD patients. The optimal cutoff values were calculated using Jorden index. Survival analysis was performed using Kaplan-Meier analysis, and log-rank test was used to compare the predictive efficacy of classification methods based on optimal cutoff values or guidance-recommended thresholds for the survival of PH-LHD patients. Variables showing statistical significance in the univariate analysis were incorporated into multivariate Cox regression model to analyze the independent risk factors for all-cause mortality.Results:A total of 243 patients were enrolled, aged (54.9±12.7) years old, including 169 (69.5%) males. During a median follow-up of 57 months, there were 101 (41.6%) deaths occurred. Grouping results were as follows: (1) TPG: TPG≤12 mmHg group 115 patients, TPG>12 mmHg group 128 patients; (2) DPG: DPG<7 mmHg group 193 patients, DPG≥7 mmHg group 50 patients; (3) PVR: PVR≤3 Wood Units group 108 patients, PVR>3 Wood Units group 135 patients; (4) TPG and PVR: TPG≤12 mmHg and PVR≤3 Wood Units group 89 patients, TPG>12 mmHg and PVR>3 Wood Units group 109 patients. PVR ( AUC=0. 698,95% CI:0.631-0.766) had better predictive value for all-cause mortality than TPG ( AUC=0.596, 95% CI: 0.523-0.669) and DPG ( AUC=0.526, 95% CI: 0.452-0.601) (all P<0.05). The optimal cutoff values for TPG, DPG, and PVR were13.9 mmHg, 2.8 mmHg, and 3.8 Wood Units, respectively. Kaplan-Meier analysis based on the optimal cutoff values or guidance-recommended thresholds showed that PVR and TPG were the predictors of survival ( P<0.05), while DPG did not showed significance ( P>0.05). Multivariate Cox regression analysis showed that age, PVR and log 2N-terminal pro-B-type natriuretic peptide were independent risk factors for all-cause mortality in PH-LHD patients (all P<0.05). Conclusion:Classification according to PVR was most valuable in predicting all-cause death in PH-LHD patients, while TPG showed moderate predictive ability and DPG had no predictive value.
10.Aprospective study of detection and clinical significance of bone marrow tumor cells in small cell lung cancer
Ying WANG ; Baohua LU ; Yuan GAO ; Yanxia LIU ; Mingming HU ; Nanying CHE ; Haifeng LIN ; Hongxia LI ; Hongmei ZHANG ; Tongmei ZHANG
Chinese Journal of Oncology 2024;46(5):419-427
Objective:To investigate the detection of bone marrow tumor cells in small cell lung cancer (SCLC) patients and their relationship with clinical features, treatment response and prognosis.Methods:A total of 113patients with newly diagnosed SCLC from January 2018 to October 2022 at Beijing Chest Hospital were prospectively enrolled. Before treatment, bone marrow was aspirated and separately submitted for tumor cells detection by liquid-based cytology and disseminated tumor cells (DTCs) detection by the substrction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) platform. The correlation between the detection results of the two methods with patients' clinical features and treatment response was evaluated by Chi-square. Kaplan-Meier method was applied to create survival curves and the Cox regression model was used for multivariate analysis.Results:The positive rate of bone marrow liquid-based cytology in SCLC was 15.93% (18/113). The liver and bone metastases rates were significantly higher (55.56% vs 11.58% for liver metastasis, P<0.001; 77.78% vs 16.84% for bone metastasis, P<0.001) and thrombocytopenia was more common (16.67% vs 2.11%, P=0.033) in patients with tumor cells detected in liquid-based cytology than those without detected tumor cells. As for SE-iFISH, DTCs were detected in 92.92% of patients (105/113), the liver and bone metastasis rates were significantly higher (37.93% vs 11.90% for liver metastasis, P=0.002; 44.83% vs 20.23 % for bone metastasis, P=0.010), and the incidence of thrombocytopenia was significantly increased (13.79% vs 1.19%, P=0.020) in patients with DTCs≥111 per 3 ml than those with DTCs<111 per 3 ml. The positive rates of bone marrow liquid-based cytology in the disease control group and the disease progression group were 12.00% (12/100) and 46.15% (6/13), respectively, and the difference was statistically significant ( P=0.002). However, the result of SE-iFISH revealed the DTCs quantities of the above two groups were 29 (8,110) and 64 (15,257) per 3 ml, and there was no statistical difference between the two groups ( P=0.329). Univariate analysis depicted that the median progression-free survival (PFS) and median overall survival (OS) of liquid-based cytology positive patients were significantly shorter than those of tumor cell negative patients (6.33 months vs 9.27 months for PFS, P=0.019; 8.03 months vs 19.50 months for OS, P=0.019, P=0.033). The median PFS and median OS in patients with DTCs≥111 per 3 ml decreased significantly than those with DTCs<111 per 3 ml (6.83 months vs 9.50 months for PFS, P=0.004; 11.2 months vs 20.60 months for OS, P=0.019). Multivariate analysis showed that disease stage ( HR=2.806, 95% CI:1.499-5.251, P=0.001) and DTCs quantity detected by SE-iFISH ( HR=1.841, 95% CI:1.095-3.095, P=0.021) were independent factors of PFS, while disease stage was the independent factor of OS ( HR=2.538, 95% CI:1.169-5.512, P=0.019). Conclusions:Both bone marrow liquid-based cytology and SE-iFISH are clinically feasible. The positive detection of liquid-based cytology or DTCs≥111 per 3 ml was correlated with distant metastasis, and DTCs≥111 per 3 ml was an independent prognostic factor of decreased PFS in SCLC.

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