1.Construction of a predictive model for the prognosis of elderly patients with advanced lung adenocarcinoma after surgery based on the SEER database
Linli CHEN ; Arun ZHANG ; Wenlu BU ; Chuanbo LIU
Cancer Research and Clinic 2024;36(1):32-40
Objective:To construct and analyze the visual nomogram predictive model for the prognosis of elderly advanced lung adenocarcinoma patients after surgery based on the Surveillance, Epidemiology, and End Results (SEER) database.Methods:SEER*Stat8.4.0.1 software was used to screen out the data from 17 register in SEER database between 2000 and 2019, and finally 4 453 lung adenocarcinoma patients aged ≥ 65 years who underwent surgical treatment and were diagnosed as stage Ⅲ and Ⅳ according to the 7th edition of the American Joint Committee on Cancer (AJCC) staging criteria were enrolled. The data were randomly divided into the training set (3 117 cases) and the validation set (1 336 cases) in a 7:3 ratio; the epidemilogical data and clinicopathological characteristics of the two groups were compared. LASSO regression was used for data dimensionality reduction to select the best predictors from the prognostic factors of patients. Cox proportional risk model was used to perform univariate and multivariate analyses of the screened variables, and based on R software rms package and the prognostic independent risk factors, the nomogram was constructed to predict the 1-, 3-, and 5-year cancer-specific survival (CSS) rates of the patients. The validation set was validated by using Bootstrap method with 1 000 equal repeated samples with playback, and the accuracy of the nomogram model was verified by using the C-index, receiving operating characteristic (ROC) curves and calibration curves.Results:There were no statistically significant differences in age, gender, race, tumor location, Grade grading, surgery methods, the number of lymph node dissection, radiotherapy, tumor diameter, tumor metastasis, marriage, living condition, TNM staging, radiochemotherapy of training set and validation set (all P > 0.05). In training set, 18 variables were included into LASSO regression analysis and were performed with dimensionality reduction; ultimately, 11 optimal predictive variables were selected, including age ≥ 85 years ( HR = 2.34, 95% CI: 1.803-3.037, P < 0.01), male ( HR = 1.326, 95% CI: 1.228-1.432, P < 0.01), Grade grading Ⅲ-Ⅳ ( HR = 1.333, 95% CI: 0.844-2.105, P < 0.01), undissected lymph nodes ( HR = 2.261, 95% CI: 2.023-2.527, P < 0.01), tumor diameter ≥3.7 cm ( HR = 1.445, 95% CI: 1.333-1.566, P < 0.01), bone metastasis ( HR = 1.535, 95% CI: 1.294-1.819, P < 0.01), brain metastasis ( HR = 1.308, 95% CI: 1.117-1.532, P < 0.01), lung metastasis ( HR = 1.229, 95% CI: 1.056-1.431, P = 0.01), living in rural areas ( HR = 1.215, 95% CI: 1.084-1.363, P < 0.01), TNM staging Ⅳ ( HR = 1.155, 95% CI: 1.044-1.278, P = 0.01), postoperative radiotherapy ( HR = 1.148, 95% CI: 1.054-1.250, P < 0.01); lung adenocarcinoma patients with the above 11 factors had worse prognosis. Based on the variables, the nomogram predictive model was constructed to predict 1-, 3-, and 5-year CSS rates of elderly advanced lung adenocarcinoma patients. Bootstrap method was used for repeated sampling for 1 000 times to verify the modeling effect of nomogram. In the model group, C-index was 0.654 (95% CI: 0.641-0.668), 0.666 (95% CI: 0.646-0.685), respectively in the training set and the validation set. The nomogram was drawn to predict ROC curves of 1-, 3-, and 5-year CSS rates for elderly advanced lung adenocarcinoma patients after operation in the training set and validation set; the area under the curve (AUC) of 1-year, 3-year, and 5-year CSS rates was 0.730 (95% CI: 0.708-0.754) and 0.689 (95% CI: 0.672-0.710), 0.687 (95% CI: 0.668-0.711) and 0.731 (95% CI: 0.697-0.765), 0.712 (95% CI:0.684-0.740) and 0.714 (95% CI: 0.683-0.745), respectively in the training and validation sets. The calibration curve showed a high consistency between the predicted probability of the model and the actual probability. Conclusions:The nomogram model constructed by optimal predictive variables for predicting the prognosis of elderly advanced lung adenocarcinoma patients after surgery may be a convenient tool for survival prediction of these patients.
2.Impact of ambient ozone exposure on death from cardiovascular and cerebrovascular diseases in Minhang District, Shanghai
Jie LIU ; Jun HUANG ; Xiaowen XU ; Lingyan ZHEN ; Linli CHEN ; Shengjie YING ; Xihao DU
Journal of Environmental and Occupational Medicine 2024;41(5):467-473
Background Ozone (O3) pollution has gradually become a primary problem of air pollution in recent years. Conducting epidemiological studies on the correlation between O3 concentration variation and risk of cardiovascular and cerebrovascular diseases can provide reference data for O3 risk assessment and related policy making. Objective To quantitatively evaluate the effects of O3 exposure on mortalities of cardiovascular and cerebrovascular diseases among residents in Minhang District, Shanghai. Methods Data of mortalities of cardiovascular and cerebrovascular diseases, air pollutants, and meteorological factors in Minhang District of Shanghai from January 1, 2016 to December 31, 2021 were collected. Associations between O3 concentration and the mortalities due to total cardiovascular and cerebrovascular diseases, coronary heart disease, and stroke were analyzed by generalized additive models with a quasi Poisson distribution with different lag patterns, such as current day effect (lag0), single-day lag effects (lag1-lag3), and cumulative lag effects (lag01-lag03). The subgroup analyses of age, sex, and season were conducted. Furthermore, temperature was divided into low, middle, and high levels based on the 25th percentile (P25) and the 75th percentile (P75) to perform hierarchical analyses. Increased excess risks (ER) of death from target diseases caused by a 10 µg·m−3 increase in daily maximum 8 h concentration of O3 (O3-8 h) and their 95% confidence intervals (CI) were used to indicate the effects of O3. Results The associations between O3 and the risks of death from cardiovascular and cerebrovascular diseases were statistically significant at lag2, lag3, lag02, and lag03 (P<0.05), with the greatest effect size observed at lag03. The ER values of death from cardiovascular and cerebrovascular diseases in general population, male residents, and people aged 65 years and older, from coronary heart disease in male residents, and from stroke in general population increased by 1.02% (95%CI: 0.36%, 1.69%), 1.40% (95%CI: 0.47%, 2.34%), 0.87% (95%CI: 0.19%, 1.55%), 1.96% (95%CI: 0.49%, 3.44%), and 1.02% (95%CI: 0.07%, 1.98%) for a 10 µg·m−3 increase in O3-8 h concentration at lag03, respectively. During the warm season (from April 1 to September 30), the ER values of death from cardiovascular and cerebrovascular diseases and coronary heart disease per 10 µg·m−3 increase in O3 were 1.18% (95%CI: 0.33%, 3.33%) and 2.69% (95%CI: 0.39%, 5.03%), while the O3 effect was only statistically significant on cardiovascular and cerebrovascular diseases during the cold season (from October 1 to March 31 next year). At the middle and high temperature levels, the ER values of death from cardiovascular and cerebrovascular diseases increased by 1.63% (95%CI: 0.32%, 2.96%) and 1.14% (95%CI: 0.17%, 2.12%) respectively. The two-pollutant models showed similar results after including other pollutants (carbon monoxide, nitrogen dioxide, sulfur dioxide, fine particulate matter, or inhalable particulate matter). Conclusion Ambient O3 pollution may increase the mortality risks of cardiovascular and cerebrovascular diseases, coronary heart disease, and stroke in Minhang District of Shanghai.
3.Interpretation of the 2023 American Burn Association "Clinical practice guidelines for burn shock resuscitation"
Linli SUN ; Lihong LIU ; Luyan XIANG ; Li DING ; Wenjun LIU
Chinese Journal of Burns 2024;40(10):996-1000
The American Burn Association updated and released the " Clinical practice guidelines on burn shock resuscitation" in December 2023. This guideline is an extension and refinement of the " Practice guidelines on burn shock resuscitation" released in 2008. It mainly provides evidence-based recommendations for acute fluid resuscitation in adults with burn shock. In order to enable clinicians to better apply the 2023 guideline, this article focuses on the interpretation of the guideline.
4.Optimization of multi-campus management in large public hospitals:a case study of 5G-empowered multi-campus homogenization at a public hospital
Xiaohui HUANG ; Sulin ZHAO ; Linli ZHOU ; Kaiqi HUANG ; Zifeng LIU ; Liang PENG
Modern Hospital 2024;24(5):711-714,718
In recent years,the"One Hospital with Multiple Campuses"model has emerged in major public hospitals across China,providing intrinsic impetus and vitality for the expansion and balanced distribution of high-quality medical re-sources.This paper analyzed the current situation and challenges of the multiple campuses development in public hospitals within China,adopting a problem-oriented approach to explore optimized path to a unified management system.The aim was to establish a collaborative management model across campuses based predicated on the homogenization of systems,management,supervi-sion,professionals,and performance.Taking the Third Affiliated Hospital of Sun Yat-sen University as a case in this study,the paper reviewed and summarized management strategies and practical experience from the aspects of management model,resource allocation,information-orientation,homogenized management,and cultural development.Additionally,the article suggested to u-tilize 5G technology to empower homogenization across campuses.In this way,the hospital's overall operational efficiency can be improved,optimize resource allocation optimized,homogenized medical services ensured,and core competitiveness enhanced.These efforts will provide a reference for the high-quality development of multi-campus public hospitals.
5.Establishment of hKDR+/+ Humanized and Rag1-/- Gene Knockout Double Genetically Modified Mouse Model
Susu LIU ; Yong WU ; Yuan CAO ; Haoyang ZHAO ; Shijie ZHAI ; Xiaowei SUN ; Linli LI ; Changfa FAN
Laboratory Animal and Comparative Medicine 2023;43(2):103-111
ObjectiveThrough improving the potential of vascular endothelial growth factor receptor (VEGFR)-humanized mouse model (hKDR+/+) with C57BL/6N background to allow the growth of different mouse tumor cell lines, to establish novel tumor-bearing mouse models which can support in vivo tumorigenesis of different mouse tumor cell lines and be used to evaluate drugs targeting VEGFR.MethodsFirstly, a method to evaluate the in vivo activity of antibody targeting VEGFR based on the hKDR+/+ humanized mouse model was established. Recombinant activating gene 1 (Rag1) knockout mice (Rag1-/-) were established using CRISPR/Cas9 technology. Then these Rag1-/- mice were crossed with hKDR+/+ mice to get a double gene modified homozygous hKDR+/+/Rag1-/- mouse model by screening. Finally, tumor cell lines derived from different mouse strains were tested on the double gene-modified mouse model to compare the differences in tumor growth. ResultsAntibodies designed for VEGFR showed significant anti-tumor activity in hKDR+/+ mice, which significantly reduced tumor volume and weight compared with the PBS group (P<0.01, P<0.05). The number of B cells and T cells in the peripheral blood of Rag1-/- mice and hKDR+/+/Rag1-/- mice decreased (P<0.05, P<0.001). Tumors were observed in hKDR+/+/Rag1-/-, Rag1-/-, wild-type, and hKDR+/+ mice after 7 d of inoculation of MC38 cells derived from C57BL/6 mice. Tumors were only observed in groups of hKDR+/+/Rag1-/- and Rag1-/- mice, but not in the wild-type and hKDR+/+ mice after 10 d of inoculation with CT26 cells derived from BALB/c mice. After 3 weeks of inoculation, the tumor volume of hKDR+/+/Rag1-/- mice was significantly larger than that of Rag1-/- mice (P<0.01). ConclusionRag1 knockout mice were obtained and a novel hKDR+/+/Rag1-/- double genes modified mouse model was further screened. The tumor cell lines from different mouse strain origins were more prone to growth in mice with Rag1 gene deficiency. The results suggest that the reduced immune response of hKDR+/+ humanized mice will improve the capacity of supporting the growth of mouse tumor lines in the model. As a result, more tumor-bearing mouse models may be constructed for the evaluation of drugs targeting VEGFR in this way.
6.Analysis of cerebrovascular disease between 1996 and 2021 in Minhang District of Shanghai
Linli CHEN ; Lijing CHEN ; Jingyi NI ; Shuili XUAN ; Wei LIU ; Xiuhong TIAN ; Yiqin GU ; Ruonan HUANG ; Weibing WANG
Shanghai Journal of Preventive Medicine 2022;34(12):1214-1218
ObjectiveTo analyze the changing trend of cerebrovascular disease burden in Minhang District of Shanghai from 1996 to 2021, and to provide scientific evidence for government to formulate targeted cerebrovascular disease prevention and control strategies. MethodsMortality, years of life lost(YLL), years of lived with disability(YLD) and disability⁃adjusted life years(DALY) were used to evaluate the burden of cerebrovascular diseases in Minhang District. Joinpoint linear regression was used to analyze the trend of disease burden. ResultsFrom 1996 to 2021, the YLL rate of cerebrovascular diseases in Minhang District showed a downward trend (whole population: APC=-1.69%, t=-6.9, P<0.05), The YLD rate of cerebrovascular diseases showed a slow upward trend (whole population: APC=1.17%, t=3.5, P<0.05), The DALY rate of cerebrovascular diseases showed a downward trend, and fluctuated since 2003 (whole population: APC= -1.43%, t=-5.6, P<0.05). The YLL rate of cerebrovascular diseases in men was higher than that in women, and the YLD rate of cerebrovascular diseases in women was higher than that in men. After 2014, the DALY of cerebrovascular diseases in men was higher than that in women. With the increase of age, the burden of cerebrovascular diseases increased, and the burden of disease increased significantly in the age group above 70. ConclusionThe burden of cerebrovascular diseases in Minhang District is at a high level, and there are differences in age, gender and other aspects. Measures such as screening, intervention and rehabilitation need to be improved to reduce disability and premature death caused by cerebrovascular diseases and to reduce the burden of cerebrovascular diseases on individuals, families and society.
7.Effectiveness, safety and cost of urinary follicle stimulating hormone in controlled ovarian stimulation in China: multi-center retrospective cohort study of 102 061 in vitro fertilization cycles
Yimin ZHU ; Yue GAO ; Donghong NAI ; Linli HU ; Lei JIN ; Ying ZHONG ; Ze WU ; Guimin HAO ; Qiongfang WU ; Yichun GUAN ; Hong JIANG ; Cuilian ZHANG ; Minli LIU ; Xiaohong WANG ; Xiaoming TENG ; Jinliang DUAN ; Liran LI ; Yue ZHANG ; Hong YE
Chinese Journal of Obstetrics and Gynecology 2022;57(7):510-518
Objective:To explore the effectiveness, safety and cost between urinary follicle stimulating hormone (uFSH) and recombinant follicle stimulating hormone (rFSH) in controlled ovarian stimulation (COS) in China.Methods:Data were collected from 16 reproductive centers in China covering oocytes collection time from May 1, 2015 to June 30, 2018. Eligible patients were over 18 years old, adopting COS with uFSH (uFSH group) or rFSH (rFSH group) as start gonadotropins (Gn), and using in vitro fertilization (IVF) and (or) intracytoplasmic sperm injection for fertilisation, excluding frozen embryo recovery cycle. Generalised estimating equation was used to address the violation of independency assumption between cycles due to multiple IVF cycles for one person and clustering nature of cycles carried out within one center. Controlling variables included age, body mass index, anti-Müllerian hormone level, cause of infertility, ovulation protocol, type of fertilisation, number of embryos transferred, number of days of Gn use.Results:Totally 102 061 cycles met eligibility criteria and were included in the analyses. In terms of effectiveness, after controlling relevant unbalanced baseline characteristics, compared with rFSH group, the high oocyte retrieval (>15 oocytes was considered high retrieval) rate of uFSH group significantly decreased in gonadotropin-releasing hormone agonist protocol ( OR=0.642, P<0.01) and in gonadotropin-releasing hormone antagonist protocol ( OR=0.556, P=0.001), but the clinical pregnancy rate per transfer cycle and the live birth rate per transfer cycle significantly increased ( OR=1.179, OR=1.169, both P<0.01) in both agonist and antagonist protocols. For safety, multiple analysis result demonstrated that in the agonist protocol, compared with rFSH group, the incidence of moderate to severe ovarian hyperstimulation syndrome of uFSH group significantly decreased ( OR=0.644, P=0.002). The differences in ectopic pregnancy rate and multiple pregnancy rate between the uFSH and rFSH groups were not significant ( P=0.890, P=0.470) in all patients. In terms of cost, compared with rFSH group, the uFSH group had lower total Gn costs for each patient ( P<0.01). Conclusion:For patients who underwent COS, uFSH has better safety, and economic profiles over rFSH in China.
8.Analysis of clinical phenotype and gene variants in a patient with classic tuberous sclerosis complex
Linli LIU ; Gaowu YAN ; Lingli DENG ; Qinglian LU ; Tingting LIU ; Fei OUYANG ; Chunshui YU
Chinese Journal of Dermatology 2022;55(8):713-716
Objective:To analyze clinical phenotypes and pathogenic mutations of a patient with classic tuberous sclerosis complex.Methods:Clinical data was collected from a patient with classic tuberous sclerosis complex. Next-generation sequencing was performed to screen pathogenic gene variants, and Sanger sequencing to verify the mutations. Minigene plasmids were constructed and transfected into the human renal epithelial cell line 293T, and RNA was extracted for transcriptional analysis.Results:The patient clinically presented with recurrent epileptic seizures, facial angiofibroma, periungual fibroma, pulmonary lymphangioleiomyomatosis, renal angiomyolipoma and multiple osteosclerosis. Next-generation sequencing revealed a suspected pathogenic variant in the TSC2 gene in the patient. Sanger sequencing identified a heterozygous mutation c.336_336+15delGGTAAGGCCCAGGGCG in exon 4 of the TSC2 gene in the patient, but not in his parents or 100 unrelated healthy controls. Moreover, this mutation had not been previously reported. The minigene experiment showed changed mRNA sequence of the TSC2 gene in this patient with loss of the authentic splice site in exon 4 and insertion of a 74-bp intron, which shifted the splice site 90 bp downstream (r.336delins336+16_336+90) .Conclusion:The novel heterozygous mutation c.336_336+15delGGTAAGGCCCAGGGCG in exon 4 of the TSC2 gene can lead to aberrant splicing, and may contribute to tuberous sclerosis complex in this patient.
9.Existing tests vs. novel non-invasive assays for detection of invasive aspergillosis in patients with respiratory diseases
Wei XIAO ; Longyi DU ; Linli CAI ; Tiwei MIAO ; Bing MAO ; Fuqiang WEN ; Gerard Peter GIBSON ; Deying GONG ; Yan ZENG ; Mei KANG ; Xinmiao DU ; Junyan QU ; Yan WANG ; Xuemei LIU ; Ruizhi FENG ; Juanjuan FU
Chinese Medical Journal 2022;135(13):1545-1554
Background::Although existing mycological tests (bronchoalveolar lavage [BAL] galactomannan [GM], serum GM, serum (1,3)-β-D-glucan [BDG], and fungal culture) are widely used for diagnosing invasive pulmonary aspergillosis (IPA) in non-hematological patients with respiratory diseases, their clinical utility in this large population is actually unclear. We aimed to resolve this clinical uncertainty by evaluating the diagnostic accuracy and utility of existing tests and explore the efficacy of novel sputum-based Aspergillus assays. Methods::Existing tests were assessed in a prospective and consecutive cohort of patients with respiratory diseases in West China Hospital between 2016 and 2019 while novel sputum assays (especially sputum GM and Aspergillus-specific lateral-flow device [LFD]) in a case-controlled subcohort. IPA was defined according to the modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Sensitivity and specificity were computed for each test and receiver operating characteristic (ROC) curve analysis was performed. Results::The entire cohort included 3530 admissions (proven/probable IPA = 66, no IPA = 3464) and the subcohort included 127 admissions (proven/probable IPA = 38, no IPA = 89). Sensitivity of BAL GM (≥1.0 optical density index [ODI]: 86% [24/28]) was substantially higher than that of serum GM (≥0.5 ODI: 38% [39/102]) ( χ2 = 19.83, P < 0.001), serum BDG (≥70 pg/mL: 33% [31/95]) ( χ2 = 24.65, P < 0.001), and fungal culture (33% [84/253]) ( χ2 = 29.38, P < 0.001). Specificity varied between BAL GM (≥1.0 ODI: 94% [377/402]), serum GM (≥0.5 ODI: 95% [2130/2248]), BDG (89% [1878/2106]), and culture (98% [4936/5055]). Sputum GM (≥2.0 ODI) had similar sensitivity (84% [32/38]) (Fisher’s exact P = 1.000) to and slightly lower specificity (87% [77/89]) ( χ2 = 5.52, P = 0.019) than BAL GM (≥1.0 ODI). Area under the ROC curve values were comparable between sputum GM (0.883 [0.812-0.953]) and BAL GM (0.901 [0.824-0.977]) ( P = 0.734). Sputum LFD had similar specificity (91% [81/89]) ( χ2 = 0.89, P = 0.345) to and lower sensitivity (63% [24/38]) ( χ2 = 4.14, P = 0.042) than BAL GM (≥1.0 ODI), but significantly higher sensitivity than serum GM (≥0.5 ODI) ( χ2 = 6.95, P = 0.008), BDG ( χ2 = 10.43, P = 0.001), and fungal culture ( χ2 = 12.70, P < 0.001). Conclusions::Serum GM, serum BDG, and fungal culture lack sufficient sensitivity for diagnosing IPA in respiratory patients. Sputum GM and LFD assays hold promise as rapid, sensitive, and non-invasive alternatives to the BAL GM test.
10.Study on the Spectrum-effect Relationship of Antioxidant Activity of Ethanol Extract from Melastoma dodecandrum
Song QIAN ; Qin LIU ; Xiuping MA ; Jing YANG ; Teng CHEN ; Jing LIU ; Linli LIU
China Pharmacy 2021;32(16):1969-1974
OBJECTIVE: To establish the fingerprint of the ethanol e xtract from Melastoma dodecandrum , to study spectrum-effect relationship of its antioxidant activity. METHODS :HPLC method and Similarity Evaluation System of TCM Chromatographic Fingerprint (2012 edition)were used to establish the fingerprints of 15 batches of ethanol extracts from M. dodecandrum,and heir similarity was evaluated. The common peaks were identified by comparing with substance control. DPPH free radical scavenging method ,ABTS free radical scavenging method and total antioxidant capacity determination method (FRAP) were used to determine antioxidant activity in vitro of 15 batches of ethanol extracts from M. dodecandrum . Principal component analysis,bivariate correlation analysis and partial least squares regression analysis were used to study the spectrum-effect relationship of the antioxidant activity of the ethanol extracts from M. dodecandrum . RESULTS :Totally 20 common peaks were identified in HPLC fingerprints of 15 batches of ethanol extracts from M. dodecandrum ;its similarity with the control fingerprint was not less than 0.831;it was identified that peak 3 was gallic acid ,peak 13 was vitexin ,peak 17 was rutin and peak 19 was ellagic acid. The IC 50 values of DPPH radical scavenging method of 15 batches of ethanol extracts from M. dodecandrum were 21.98-57.87 μ g/mL,that of ABTS radical scavenging method were 40.94-101.88 μ g/mL,the results of FRAP method were 0.19-0.48 mg/mL. Principal component analysis showed that the contribution rate of IC 50 variance of DPPH was 80.77%. Bivariate correlation analysis showed that the peak areas of peak 2 (positive correlation ) and peak 11 (negative correlation ) were significantly correlated with antioxidant activity (P<0.05);partial least squares regression analysis showed that ,the variable projection importance (VIP)in descending order was peak 11>peak 2>peak 16>peak 15>peak 12>peak 13>peak 18,and their VIP values were greater than 1. Peaks 2,13,15,16 and 18 were positively correlated with antioxidant activity ,and peaks 11 and 12 were negatively correlate d with antioxidant activity ,and the absolute value of standardized regression coefficient were greater than 0.1. CONCLUSIONS :Fifteen batches of ethanol extracts of M. dodecandrum have antioxidant activity in vitro . The compounds corresponding to common peaks 2,11,12, 13,15,16 and 18 may be the material basis of antioxidant activity of M. dodecandrum .

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