1.Mechanisms of reproductive toxicity and ferroptosis induced by polystyrene microplastics in male mice
Jiabo WANG ; Rong LI ; Setiniaz NAZIRA ; Chengqing LIU ; Nan YANG ; Qi YAN
Journal of Environmental and Occupational Medicine 2025;42(2):224-231
Background Polystyrene microplastics (PS-MPs) attract widespread public attention due to their adverse effects on mammalian reproductive systems. However, it is currently unclear whether ferroptosis is related to testicular damage and decreased sperm quality in mice exposed to PS-MPs. Objective To clarify the reproductive damage in male mice exposed to PS-MPs and investigate the mechanism of ferroptotic effects. Methods Five-week-old male BALB/c mice were randomly divided into four experimental groups, including one control group and three PS-MPs groups at low dose (0.5 mg·kg−1), medium dose (5 mg·kg−1), and high dose (50 mg·kg−1), respectively, with 6 mice in each group. The treatment was delivered by gavage for 35 consecutive days (one time per day). After the mice were neutralized, the wet weights of testis and epididymis were measured, and organ coefficients were then calculated. Sperm was counted by hematimetry, and sperm motility and adenosine triphosphate (ATP) level were evaluated using CCK-8 and CellTiter Glo ® Kit 2.0 Assay respectively. In addition, serum testosterone, follicle-stimulating hormone, and luteinizing hormone were determined using ELISA kit, total testicular iron content was measured using tissue iron kit, and pathological changes in testicular tissue were observed after hematoxylin-eosin (HE) staining. We also used glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) assays to examine their changes to better understand the physiological status of testicular tissue. Finally, the expression levels of ferroptosis-associated proteins glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) were detected by Western blotting. Results Compared with the control group, the testicular index in the high dose group decreased, and the epididymal index decreased in all dose groups (P<0.05). The results of sperm quality analysis showed that the sperm count in each dose group was lower than that of the control group; the sperm motility decreased, sperm malformation rate increased, and ATP level in sperm decreased in the medium and high dose groups. The results of HE staining showed that the spermatogenic epithelium was disordered and the arrangement of spermatogenic cells were loose in the low dose group, the spermatogenic gap was enlarged in the middle dose group, and the cells in the high dose group were vacuolated and even azoospermic. The results of serum sex hormone levels showed that the serum testosterone levels decreased in each dose group, the serum follicle-stimulating hormone levels decreased in the medium and high dose groups, and the serum luteinizing hormone levels decreased in the high dose group (P<0.05). The iron content in the testicular tissue homogenate of the high dose group increased (P<0.05). The levels of GSH and SOD in the homogenate of testicular tissue decreased in the medium and high dose groups, while the levels of MDA increased (P<0.05). The results of Western blotting showed that the protein expression level of GPX4 in the testis in the high dose group was lower than that in the control group. The protein expression levels of SLC7A11 in the medium and high dose groups were lower than that in the control group. The results of correlation analysis showed that the expression level of GPX4 was positively correlated with sperm count, and negatively correlated with MDA level (P<0.05). SLC7A11 expression level was positively correlated with sperm count, and negatively correlated with sperm malformation rate and MDA level (P<0.05). Conclusion PS-MPs exposure leads to decreased sperm quality, testicular damage, and decreased serum sex hormone levels in male mice, and its mechanism of action may involve ferroptosis.
2.Bioinformatics-based construction of a cervical cancer prognosis-associated competing endogenous RNA network
Jingqin REN ; Changhui ZHOU ; Chengqing LIU ; Nazila SAITINIYAZI ; Nan YANG ; Rong LI
Journal of China Medical University 2024;53(5):385-391
Objective To comprehensively analyze the circulatory RNA-long non-coding RNA-microRNA-messenger RNA(circRNA-lncRNA-miRNA-mRNA)network in cervical cancer and construct a prognostic model.Methods Differential and key genes were ana-lyzed using bioinformatics based on data from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.Prognostic mRNA models were constructed based on TCGA database using univariate,Least Absolute Shrinkage and Selection Operator(LASSO),and multivariate Cox regression analyses and validated using the GEO database.The R package and Cystoscape software were used to construct a nomogram model and competing endogenous(ceRNA)network of circRNA-lncRNA-miRNA-mRNA in cervical cancer.Results A prognostic model including five mRNAs was constructed using univariate,LASSO,and multivariate Cox regression analyses,which had area under the receiver operating characteristic curve AUC values of 0.71,0.71,and 0.70 at 1,2,and 3 years,respec-tively,indicating its sensitivity and specificity in cervical cancer prognosis.Predictive results were validated using the GSE44001 dataset.The C-index of the nomogram model for this prognostic model was 0.707.In this study,a ceRNA network comprising 39 circRNAs,27 lncRNAs,12 miRNAs,and five mRNAs was constructed.Conclusion The network constructed in this study can help comprehensively elucidate the mechanism of ceRNAs in cervical cancer,and the construction of prognostic and Nomogram models can predict patient prog-nosis.
3.Evaluation of Molecular Residual Disease by a Fixed Panel in Resectable Colorectal Cancer
Jian YANG ; Chengqing YU ; Haoran LI ; Di PENG ; Qiaoxia ZHOU ; Jun YAO ; Juan LV ; Shuai FANG ; Jiaochun SHI ; Yijun WEI ; Guoqiang WANG ; Shangli CAI ; Zhihong ZHANG ; Zixiang ZHANG ; Jian ZHOU
Cancer Research and Treatment 2024;56(4):1183-1196
Purpose:
Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC.
Materials and Methods:
Seventy-five patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and preoperative and postoperative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients.
Results:
The tumor-informed fixed assay had a higher preoperative positive rate than the tumor-agnostic assay (73.3% vs. 57.3%). The preoperative ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined postoperative ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR], 20.74; 95% confidence interval [CI], 7.19 to 59.83; p < 0.001), which was an independent predictor by multivariable analysis (HR, 28.57; 95% CI, 7.10 to 114.9; p < 0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest preoperative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in postoperative landmark (HR, 26.34; 95% CI, 6.01 to 115.57; p < 0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04; 95% CI, 0.94 to 9.89; p=0.052).
Conclusion
Our study confirmed the prognostic value of the ctDNA positivity at postoperative day 7 by the tumor-informed fixed panel. The tumor-informed fixed panel may be a cost-effective method to evaluate MRD, which warrants further studies in future.
4.Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly (version 2023)
Yan HU ; Dongliang WANG ; Xiao CHEN ; Zhongmin SHI ; Fengjin ZHOU ; Jianzheng ZHANG ; Yanxi CHEN ; Liehu CAO ; Sicheng WANG ; Jianfei WANG ; Hongliang WANG ; Yong FENG ; Zhimin YING ; Chengdong HU ; Qinglin HAN ; Ming LI ; Xiaotao CHEN ; Zhengrong GU ; Biaotong HUANG ; Liming XIONG ; Yunfei ZHANG ; Zhiwei WANG ; Baoqing YU ; Yong WANG ; Lei ZHANG ; Lei YANG ; Peijian TONG ; Ximing LIU ; Qiang ZHOU ; Feng NIU ; Weiguo YANG ; Wencai ZHANG ; Shijie CHEN ; Jinpeng JIA ; Qiang YANG ; Tao SHEN ; Bin YU ; Peng ZHANG ; Yong ZHANG ; Jun MIAO ; Kuo SUN ; Haodong LIN ; Yinxian YU ; Jinwu WANG ; Kun TAO ; Daqian WAN ; Lei WANG ; Xin MA ; Chengqing YI ; Hongjian LIU ; Kun ZHANG ; Guohui LIU ; Dianying ZHANG ; Zhiyong HOU ; Xisheng WENG ; Yingze ZHANG ; Jiacan SU
Chinese Journal of Trauma 2023;39(4):289-298
Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.
5.Function-preserving laparoscopic pancreatic surgery: A reasonable choice in pancreatic surgery
Journal of Clinical Hepatology 2022;38(12):2696-2700
With the improvement of diagnostic techniques, the diagnostic rate of pancreatic tumors has increased significantly, with a tendency of an earlier age of onset. Since the pancreas is an important endocrine organ, the loss of pancreatic function will have a serious impact on the quality of life of patients. Therefore, function-preserving laparoscopic pancreatic surgery with little trauma is an ideal method for the treatment of benign and low-grade malignant pancreatic lesions and is also a direction for exploration in pancreatic surgery. Pancreatic tumor enucleation, duodenum-preserving pancreatic head resection, and spleen-preserving distal pancreatectomy are commonly used surgical procedures for preserving pancreatic function in clinical practice nowadays. This article introduces commonly used surgical procedures for function-preserving laparoscopic pancreatic surgery and provides some surgical skills to help choose a reasonable surgical procedure and make individualized decisions on pancreatic surgery for patients.
6.Artificial intelligence-assisted diagnosis and treatment system in prediction of benign or malignant lung nodules and infiltration degree
Mengkun CAO ; Jie JIANG ; Xiaolei ZHU ; Ning LI ; Jianweng WANG ; Junfeng LIN ; Hongming LIU ; Chengqing DENG ; Xiqian CAI ; Guojun GENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2021;28(03):283-287
Objective To evaluate the effectiveness of the artificial intelligence-assisted diagnosis and treatment system in distinguishing benign and malignant lung nodules and the infiltration degree. Methods Clinical data of 87 patients with pulmonary nodules admitted to the First Affiliated Hospital of Xiamen University from January 2019 to August 2020 were retrospectively analyzed, including 33 males aged 55.1±10.4 years, and 54 females aged 54.5±14.1 years. A total of 90 nodules were included, which were divided into a malignant tumor group (n=80) and a benign lesion group (n=10), and the malignant tumor group was subdivided into an invasive adenocarcinoma group (n=60) and a non-invasive adenocarcinoma group (n=20). The malignant probability and doubling time of each group were compared and its ability to predict the benign and malignant nodules and the invasion degree was analyzed. Results Between the malignant tumor group and the benign lesion group, the malignant probability was significantly different, and the malignant probability could better distinguish malignant nodules and benign lesions (87.2%±9.1% vs. 28.8%±29.0%, P=0.000). The area under the curve (AUC) was 0.949. The maximum diameter of nodules in the benign lesion group was significantly longer than that in the malignant tumor group (1.270±0.481 cm vs. 0.990±0.361 cm, P=0.026); the doubling time of benign lesions was significantly longer than that of malignant nodules (1 083.600±258.180 d vs. 527.025±173.176 d, P=0.000), and the AUC was 0.975. The maximum diameter of the nodule in the invasive adenocarcinoma group was longer than that of the non-invasive adenocarcinoma group (1.350±0.355 cm vs. 0.863±0.271 cm, P=0.000), and there was no statistical difference in the probability of malignancy between the invasive adenocarcinoma group and the non-invasive adenocarcinoma group (89.7%±5.7% vs. 86.4%±9.9%, P=0.082). The AUC was 0.630. The doubling time of the invasive adenocarcinoma group was significantly shorter than that of the non-invasive adenocarcinoma group (392.200±138.050 d vs. 571.967±160.633 d, P=0.000), and the AUC was 0.829. Conclusion The malignant probability and doubling time of lung nodules calculated by the artificial intelligence-assisted diagnosis and treatment system can be used in the assessment of the preoperative benign and malignant lung nodules and the infiltration degree.
7.Analysis of a family with asparagine synthase deficiency caused by ASNS gene mutation and literature review
Zhenfeng SONG ; Zhi YI ; Fei LI ; Chengqing YANG ; Jiao XUE ; Kaixuan LIU ; Ying ZHANG
Chinese Journal of Applied Clinical Pediatrics 2021;36(9):690-693
Objective:To investigate the clinical characteristics and gene variation of asparagine synthase deficiency that is caused by ASNS gene variation. Methods:In Department of Neuroendocrine Pediatrics, Affiliated Hospital of Qingdao University from October 2018 to February 2020, the clinical data of a family of asparagine synthase deficiency were analyzed retrospectively.The pathogenic mutation of the proband was screened by the full exon analysis technique.The pathogenic sites of candidate genes were determined by combining the phenotype of the proband.In the heterotopic spot of the proband, his parents and other family members were verified by Sanger sequencing.Meanwhile, the relevant literature database was consulted, and the reported ASNS mutation related cases were collected and reviewed. Results:The female with proband visited the hospital at the age of 4 months, and she had recurrent convulsions at the age of about 3 months.Physical examination showed that the child suffered from microcephaly, and mental and motor retardation.Meanwhile, video electroencephalogram examination displayed extensive moderate high amplitude spiny slow wave and sharp slow wave.Exon sequencing illustrated that the compound heterozygous variants of ASNS gene were c. 1211G>A (p.R404H) and c. 1643C>T (p.S548F), respectively.c.1211G>A was a known pathogenic variant, and c. 1643C>T was a new variant.The proband′s younger brother visited the hospital at the age of 2 months, developed convulsions at the age of 1 month, and developed mental and motor retardation.Electroencephalogram displayed that bilateral posterior head was dominant, multiple foci and extensive spike wave, and spike slow wave and fast wave were distributed.Sanger sequencing revealed the same ASNS compound heterozygous variants as the proband.Both of them died of status convulsion at the age of 7 months and 6 months, respectively. Conclusions:This study is helpful to further understand the clinical features of the disease and reveal a new pathogenic mutation of ASNS gene, so as to enrich the mutation spectrum of ASNS gene, thus providing important basis for clinical treatment and genetic counseling.
8.Comparison of HRCT imaging features of ground glass opacity of COVID-19 and early-stage lung carcinoma
Guojun GENG ; Xiaolei ZHU ; Yanjun MI ; Wei XIONG ; Fan OU ; Ning LI ; Hongming LIU ; Mengkun CAO ; Chengqing DENG ; Sien SHI ; Xiuyi YU ; Jie JIANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2020;36(7):393-396
Objective:To investigate the difference of HRCT imaging features between COVID-19 and the ground-glass opacity(GGO) lesion of early-stage lung carcinoma, standardize the diagnosis and treatment process of ground-glass opacity(GGO) degeneration during the epidemic.Methods:A total of 34 patients with diagnosed COVID-19 who confirmed by positive results of the new coronavirus nucleic acid test were collected as observation group 40 patients with pathologically diagnosed early-stage lung carcinoma whose preoperative HRCT examination showed pure ground glass lesions and received surgical intervention were recruited from the Department of Thoracic Surgery (The First Affiliated Hospital of Xiamen University) from January 2018 to December 2019 as the control group. The HRCT imaging features of these two groups of patients were compared and statistically analyzed.Results:The HRCT imaging features of the new type of COVID-19 showed significant difference by characteristics of multiple lesions, lesion rapid variation within 3 days, reticular pattern, vacuolar sign and clear boundary compared to the GGO lesion of early-stage lung carcinoma( P<0.05). The chinical and imaging characteristic the sex, age, with pleural effusion or not and the lesion location showed no significant difference between these 2 groups ( P>0.05). Conclusion:Contrast with inert early lung carcinoma lesions, COVID-19 disease developed rapidly. Imaging dynamic examination can provide evidences to distinguish Novel Coronavirus Pneumonia and early-stage lung carcinoma.
9.A high risk factors clinical study of low birth weight premature infants with wheezing
Jin GAO ; Dongmei YE ; Xiaojie PAN ; Mei ZHAO ; Lingyun BAO ; Ming LI ; Lin WANG ; Chengqing WU
Chinese Journal of Applied Clinical Pediatrics 2018;33(2):120-123
Objective To investigate the high risk factors for wheezing of low birth weight premature infants with wheezing.Methods A cohort study of 143 premature infants,whose gestation less than 37 weeks and birth weight less than 2 500 g,were collected from Neonatal Intensive Care Unit of Kunming Children's Hospital,from December 2012 to November 2013.Follow-up investigation was conducted,and those with wheezing were enrolled in the study.Many possible factors causing wheezing were analyzed,such as general conditions in the neonatal period,family conditions,and treatment.SPSS 17.0 statistical software was used to analyze the data.Single factor analysis was used by x2 test and rank sum test to evaluate the possible risk factors.Multiple factors analysis was made by Logistic regression analysis.P < 0.05 was viewed as having statistical difference.Results (1) The risk factors for wheezing in the premature infants were:continuous positive airway pressure (CPAP) noninvasive ventilation (x2 =8.531,P =0.003),ventilation (x2 =4.800,P =0.028),caesarean section (x2 =6.787,P =0.009),the use of pulmonary surfactant (x2 =5.455,P =0.020),using antibiotics used at hospital (x2 =5.192,P =0.023),father smoking(x2 =5.406,P =0.020),maternal smoking (x2 =8.531,P =0.003),maternal allergic history (x2 =8.297,P =0.004),compatriot history of allergies (x2 =8.297,P =0.004) or asthma (x2 =9.774,P =0.002),family environment with dust and excitant gas (x2 =12.831,P =0.000) were the risk factors for the wheezing in the low birth weight premature infants.(2)Multi-factor classification Logistic regression analysis showed that CPAP (OR =58.414,95 % CI:3.317-1 028.646,P =0.005),mother smoking during pregnancy (OR =11.953,95 % CI:1.309-109.120,P =0.028),compatriot history of allergies (OR=135.769,95% CI:4.914-3 751.419,P =0.004),family environment(OR =83.738,95% CI:4.416-1 587.982,P =0.003),were independent risk factors for wheezing in low birth weight premature infants;natural labor was protective factor for wheezing in low birth weight premature infants (OR =0.045,95% CI:0.004-0.574,P =0.017).(3)The sensitivity and specificity of risk factors were analyzed.The highest sensitivity was estimated for the father's history of allergy(83.3%).The highest specificity was estimated for the use of antibiotics at hospital (76.7%).Conclusions The study shows that CPAP noninvasive ventilation,mother smoking during pregnancy,allergy history of their brothers and sisters,family environment with dust and excitant gas are independent risk factors for wheezing in the low birth weight premature infants.There is no single risk factor with both high sensitivity and high specificity.
10.Levels of Interleukin-4, Interleukin-6 and Interferon-gamma in Bronchoalveolar Lavaga Fluid of Children with Refractory Mycoplasma Pneumoniae Pneumonia and the Features of Bronchoscopy
Li TAN ; Chengqing WU ; Yuxing SUN ; Zhengyan GAN
Journal of Kunming Medical University 2016;37(7):70-73
Objective To explore the interleukin-4 (IL-4),interleukin-6 (IL-6),interferon-gamma (IFN-γ) levels in bronchoalveolar lavage fluid (BALF) of children with refractory mycoplasma pneumoniae pneumonia,and the features of bronchoscopy.Methods A total of 47 children with refractory mycoplasma pneumoniae pneumonia were selected as the observation group,28 children with bronchial foreign body in GAN zhengyan were chosen as controls during the same period.ELISA method was used to detect the IL-4,IL-6,IFN-γ levels in the BALF,and compared them in these two groups.The bronchoscope features of the observation group were observed.Results The IL-4,IL-6,IFN-γ levels in the BALF of children in the observation group were (8.3 ± 3.1) pg/mL,(62.3 ± 18.4) pg/mL,(76.5 ± 21.9) pg/mL,and they were significantly higher than those of the controls (3.1 ± 1.2) pg/m L,(30.0 ± 1.5) pg/m L,(31.3 ± 24.9) pg/mL (P <0.05,respectively).In the observation group,the bronchial mucosa congestion and edema were observed in all patients,there were variable amounts of mucus secretions.There were other changes include:microtubule reductus (68.1%),bronchial mucosal follicle-like hyperplasia (38.3%),mucosal erosions (8.5%),airway inflammatory stenosis,mucus plug blocking (59.6%),granulation proliferation (14.9%),bronchial obliteration (4.3%) Conclusions The IL-4,IL-6,IFN-γ levels in the BALF of children with RMPP significantly increased.This indicates a significant local inflammatory response in children with RMPP.Mycoplasma pneumoniae pneumonia (MPP) has certain features of bronchoscope,these features are helpful to the diagnosis and treatment of MPP.

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