1.Clinical observation of regional citrate anticoagulation in pediatric plasma exchange
Wei DANG ; Fan ZHANG ; Yunxia LI ; Jie CHEN ; Xia LIN ; Sufang ZHANG ; Weifeng LU
Chinese Journal of Emergency Medicine 2025;34(6):795-802
Objective:To evaluate the efficacy and safety of regional citrate anticoagulation (RCA) during plasma exchange (PE) in pediatric patients.Methods:We conducted a retrospective analysis of 12 critically ill children admitted to the Pediatric Intensive Care Unit (PICU) of Jinan Children's Hospital, who underwent 28 PE sessions with RCA between December 2023 and August 2024. Clinical records were reviewed to assess bleeding events, extracorporeal circuit performance, and changes in arterial blood gas parameters, serum total calcium (Ca tot), and activated clotting time before and after treatment. Results:No patients exhibited signs of increased bleeding. In one case, the procedure was discontinued prematurely due to elevated venous pressure. A significant decrease in ionized calcium (Ca ion) was observed 0.5 hours post-treatment. At the end of PE, pH, HCO 3?, base excess (BE), lactate, PaCO 2, Ca tot, and Na + levels increased, while K + and Ca ion levels decreased, with all changes being statistically significant. Four hours post-treatment, pH, HCO 3?, BE, PaCO 2, and Na + remained elevated, whereas Ca ion, lactate, and K + returned to baseline. By 12–15 hours post-treatment, all parameters—including pH, HCO 3?, BE, PaCO 2, Na +, K +, Ca ion, and lactate—had normalized, showing no significant differences from pre-treatment levels. Conclusions:RCA provides effective extracorporeal anticoagulation during pediatric PE without increasing bleeding risk. However, metabolic complications—primarily metabolic alkalosis—are common. These disturbances typically resolve spontaneously and do not lead to severe adverse events. While no ideal anticoagulant for PE has yet been established, RCA remains a safe and effective option, particularly for pediatric patients at higher risk of bleeding.
2.Correlation analysis of central venous oxygen saturation-related indexes at different time points with low cardiac output syndrome in children after congenital heart disease correction surgery
Jingxiao LI ; Yunkai CAI ; Binfeng LEI ; Wei LU ; Liqin MO ; Weifeng HUANG ; Chaohai LYV ; Liuying QIN ; Jingwei JIANG ; Ting ZHOU
Chongqing Medicine 2025;54(5):1155-1160
Objective To explore the correlation between central venous oxygen saturation(ScvO2)-re-lated indexes at different time points and the occurrence of low cardiac output syndrome(LCOS)after con-genital heart disease(CHD)correction surgery.Methods A total of 73 children who underwent CHD correc-tion surgery in this hospital from July 1st,2021 to July 1st,2024 were selected as the research subjects.The clinical data,preoperative conditions,and postoperative conditions of the children were collected.The ScvO2 and arterial lactate(Lac)levels of the children at different time points(the 1st,6th,12th,and 24th hours after surgery)were monitored,and the ScvO2/Lac at different time points and the change rate of ScvO2 in different time periods were calculated.The correlation between ScvO2-related indexes and LCOS after CHD correction surgery was analyzed.Results ScvO2 at the 6th hour after surgery,ScvO2 at the 12th hour after surgery,Sc-vO2/Lac at the 12th hour after surgery,the change rate of ScvO2 from the 1st to the 24th hour after surgery,the change rate of ScvO2 from the 6th to the 12th hour after surgery,and the change rate of ScvO2 from the 12th to the 24th hour after surgery were independent influencing factors of LCOS occurrence after CHD cor-rection surgery(P<0.05).There was a negative correlation between ScvO2 at the 12th hour after surgery,ScvO2/Lac and LCOS occurrence after CHD correction surgery(r=-0.543,-0.523,P<0.05).The area under the curve(AUC)of ScvO2 at the 12th hour after surgery for predicting LCOS occurrence after CHD correction surgery was 0.938(95%CI:0.865-1.000);the AUC of ScvO2/Lac at the 12th hour after surgery for predicting LCOS occurrence after CHD correction surgery was 0.922(95%CI:0.851-0.994).Conclusion ScvO2 and ScvO2/Lac at the 12th hour after surgery have good predictive potential for LCOS occurrence af-ter CHD correction surgery.
3.Development and application on a full process disease diagnosis and treatment assistance system based on generative artificial intelligence.
Wanjie YANG ; Hao FU ; Xiangfei MENG ; Changsong LI ; Ce YU ; Xinting ZHAO ; Weifeng LI ; Wei ZHAO ; Qi WU ; Zheng CHEN ; Chao CUI ; Song GAO ; Zhen WAN ; Jing HAN ; Weikang ZHAO ; Dong HAN ; Zhongzhuo JIANG ; Weirong XING ; Mou YANG ; Xuan MIAO ; Haibai SUN ; Zhiheng XING ; Junquan ZHANG ; Lixia SHI ; Li ZHANG
Chinese Critical Care Medicine 2025;37(5):477-483
The rapid development of artificial intelligence (AI), especially generative AI (GenAI), has already brought, and will continue to bring, revolutionary changes to our daily production and life, as well as create new opportunities and challenges for diagnostic and therapeutic practices in the medical field. Haihe Hospital of Tianjin University collaborates with the National Supercomputer Center in Tianjin, Tianjin University, and other institutions to carry out research in areas such as smart healthcare, smart services, and smart management. We have conducted research and development of a full-process disease diagnosis and treatment assistance system based on GenAI in the field of smart healthcare. The development of this project is of great significance. The first goal is to upgrade and transform the hospital's information center, organically integrate it with existing information systems, and provide the necessary computing power storage support for intelligent services within the hospital. We have implemented the localized deployment of three models: Tianhe "Tianyuan", WiNGPT, and DeepSeek. The second is to create a digital avatar of the chief physician/chief physician's voice and image by integrating multimodal intelligent interaction technology. With generative intelligence as the core, this solution provides patients with a visual medical interaction solution. The third is to achieve deep adaptation between generative intelligence and the entire process of patient medical treatment. In this project, we have developed assistant tools such as intelligent inquiry, intelligent diagnosis and recognition, intelligent treatment plan generation, and intelligent assisted medical record generation to improve the safety, quality, and efficiency of the diagnosis and treatment process. This study introduces the content of a full-process disease diagnosis and treatment assistance system, aiming to provide references and insights for the digital transformation of the healthcare industry.
Artificial Intelligence
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Humans
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Delivery of Health Care
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Generative Artificial Intelligence
4.Relationship between high-density lipoprotein subfraction cholesterol and their subtypes with coronary heart disease and disease progression
Yutong WU ; Shaoyi LIN ; Wei HU ; Weifeng XU ; Shenghuang WANG ; Xiaomin CHEN
Chinese Journal of Laboratory Medicine 2025;48(7):888-894
Objective:To investigate the impact of high-density lipoprotein (HDL) subfraction cholesterol, measured by the vertical auto profile (VAP) technique based on vertical density gradient ultracentrifugation, on the occurrence and progression of coronary heart disease.Methods:This retrospective case-control study consecutively enrolled 94 inpatients diagnosed with coronary artery disease (CAD) by percutaneous coronary angiography at Ningbo University Affiliated First Hospital between June 2023 and June 2024 (CAD group), and 48 outpatients from the cardiology department without carotid or coronary atherosclerosis(non-CAD group). The VAP technique was employed to measure HDL subfraction cholesterol levels (HDL 3-C and HDL 2-C) and their subtypes (HDL 2a-C, HDL 2b-C, HDL 2c-C; HDL 3a-C, HDL 3b-C, HDL 3c-C, HDL 3d-C). Logistic regression analysis was performed to assess the association between HDL subfraction composition and CAD. CAD patients were further stratified by the number of affected coronary vessels (left anterior descending artery, left circumflex artery, and right coronary artery): 44 with single-vessel disease, 22 with double-vessel disease, and 28 with triple-vessel disease for correlation analysis. All CAD patients underwent 6-month clinical and telephone follow-up to record major adverse cardiovascular events (MACE), including acute myocardial infarction, stroke, and repeat revascularization. Using the median HDL 3d-C level (0.064 mmol/L) as cutoff, CAD patients were divided into high-level ( n=48) and low-level ( n=46) subgroups for Kaplan-Meier survival analysis with log-rank testing. Results:Compared with non-CAD controls, CAD patients showed significantly higher HDL 3d-C [0.064 (0.041, 0.095) mmol/L vs 0.055 (0.038, 0.067) mmol/L] and HDL 3b-C [0.031 (0.001, 0.054) mmol/L vs 0.007 (0.004, 0.029) mmol/L], lower HDL 3c-C (0.220±0.080 mmol/L vs 0.254±0.062 mmol/L) and HDL 3a-C [0.282 (0.224, 0.351) mmol/L vs 0.334 (0.269, 0.433) mmol/L] (all P<0.05). Logistic regression revealed that HDL2b-C was a protective factor against atherosclerosis severity ( OR=0.914, 95% CI 0.896-0.987, P<0.001); HDL 3d-C served as both a CAD risk factor ( OR=2.303,95% CI 1.740-3.047, P<0.001) and disease progression indicator ( OR=1.224, 95% CI 1.123-1.335, P=0.025). MACE patients ( n=6) had elevated HDL3d-C versus non-MACE cases ( n=88) [0.120 (0.083, 0.173) mmol/L vs 0.061 (0.037, 0.092) mmol/L, P<0.05]. The high HDL 3d-C subgroup demonstrated significantly lower 6-month survival (χ2=4.777, P=0.029). Conclusion:Contrary to conventional understanding, our study reveals that HDL2b serves as a protective factor against coronary artery disease progression, whereas HDL 3d-C acts not only as a pathogenic factor for CAD but also as a critical determinant of CAD-related adverse events.
5.USP21 negative regulates RLR pathway by stabilizing EV-A71 2A pro to promote EV-A71 replication
Xinyu YANG ; Mengyuan TANG ; Zhiping CHE ; Yan CHEN ; Yang PENG ; Jinhong MA ; Weifeng SHI ; Wei ZHOU
Chinese Journal of Experimental and Clinical Virology 2025;39(1):18-26
Objective:To investigate the role of ubiquitin-specific protease 21 (USP21) in enterovirus group A type 71 (EV-A71) infection.Methods:Peripheral blood mononuclear cells (PBMC) were obtained from a cohort of 24 children infected with EV-A71 and 24 healthy children. Expression of USP21 was determined by real-time fluorescence quantitative PCR (qPCR). Additionally, the impact of USP21 overexpression or knockout on EV-A71 replication was evaluated using a combination of qPCR and western blot (WB) analysis. Furthermore, WB was employed to measure the levels of EV-A71 structural protein VP1, phosphorylated interferon regulatory factor 3 (IRF3) and other key molecules in the RIG-I-like receptor (RLR) signaling pathway. Co-immunoprecipitation (Co-IP) was utilized to investigate the effects of USP21 on the ubiquitin levels of EV-A71 nonstructural protein 2A protease (2A pro). Results:In comparison to healthy children, the expression of USP21 mRNA in PBMC of children infected with EV-A71 was notably elevated. The overexpression of USP21 significantly enhanced the cytopathic effects induced by EV-A71, upregulated levels of VP1 mRNA and protein, and facilitated EV-A71 replication, leading to a decrease in cell activity with increasing levels of USP21 transfection. Following the knockout of the USP21 gene, the VP1 mRNA levels were significantly declined in comparison to the control group. Furthermore, the overexpression of USP21 was found to have no impact on the transcriptional activity of EV-A71 2A pro. However, it was observed to enhance the expression of 2A pro protein, reduce the ubiquitination of 2A pro, suppress the protein levels of mitochondrial antiviral signaling protein (MAVS) and melanoma differentiation-associated gene 5 (MDA5), as well as decrease the phosphorylation of IRF3. Additionally, the induction of IFN-β mRNA by EV-A71 infection was downregulated. Conclusions:USP21 has been shown to enhance the replication of EV-A71 through the downregulation of 2A pro ubiquitination, suppression of MAVS and MDA5 protein expression, and inhibition of the interferon signaling pathway.
6.Analysis of diagnosis and treatment of granulomatous prostatitis
Yirui WEI ; Dawei XIE ; Weifeng HE ; Hao WANG ; Pushen YANG ; Jianwen WANG
Chinese Journal of Urology 2025;46(9):698-703
Objective:To investigate the clinical diagnosis and treatment of granulomatous prostatitis(GP)in patients with Prostate Imaging Reporting and Data System(PI-RADS)scores ≥ 4 on magnetic resonance imaging(MRI).Methods:The data of 12 GP patients with PI-RADS score ≥ 4 who were admitted to Beijing Chaoyang Hospital,Capital Medical University,from February 2015 to February 2025,were retrospectively analyzed. The patients were aged 51?73 years(mean 66 years). Presenting complaints included elevated prostate-specific antigen(PSA)levels in 6 cases,prostatic mass in 2 cases,urinary retention in 3 cases,and gross hematuria in 1 case. All 12 patients had concomitant lower urinary tract symptoms. Medical history revealed pulmonary tuberculosis in 2 cases,testicular tuberculosis in 1 case,close contact with tuberculosis in 1 case(spouse diagnosed with pulmonary tuberculosis 5 years earlier),allergic granulomatous vasculitis in 1 case,and intravesical bacillus Calmette-Guérin(BCG)instillation in 1 case. Digital rectal examination(DRE)showed gradeⅠprostatic hyperplasia in 2 cases,grade Ⅱ in 9 cases,and grade Ⅲ in 1 case. Nodules were palpable in 6 patients. The median PSA was 7.20 ng/ml(ranging 1.11?21.90 ng/ml),with 2 cases < 4 ng/ml. Transrectal ultrasound was performed in 10 patients,and prostate volumes were ranging from 29.48 to 109.78 cm3,with 6 cases > 45 cm3. All 12 patients underwent MRI,and all demonstrated PI-RADS scores ≥ 4,typically presenting as low signal intensity on T2-weighted imaging,high signal on diffusion-weighted imaging(DWI),and low apparent diffusion coefficient(ADC)values. Contrast-enhanced MRI in 8 cases revealed heterogeneous enhancement. One patient underwent 68Ga-prostate-specific membrane antigen positron emission tomography-computed tomography( 68Ga-PSMA PET-CT),which showed band-like increased uptake in the central zone. All 12 patients were preoperatively suspected of prostate cancer,of whom 10 underwent transrectal biopsy and 2 underwent transperineal biopsy. Pathological characteristics and follow-up results were analyzed. Treatment outcomes were analyzed,The International Prostate Symptom Score(IPSS),quality of life(QOL)score,maximum urinary flow rate(Q max),and post-void residual urine(PVR)volume were compared before and 1 month after treatment. Results:Histopathology confirmed GP in all cases,with chronic inflammation in 11 cases and acute inflammation in 1 case. Immunohistochemistry demonstrated positivity for CD68(macrophage marker),high-molecular weight cytokeratin(HCK),and reticulin staining;periodic acid-Schiff(PAS)and acid-fast staining were positive in 2 cases,corresponding to 1 patient with a prior history of pulmonary tuberculosis and 1 with testicular tuberculosis. Two patients underwent thulium laser enucleation of the prostate,while 10 received conservative treatment,including 2 patients with tuberculosis infection who were referred for anti-tuberculosis therapy and 8 patients treated with oral tamsulosin 0.2 mg once daily. Follow-up was completed in 10 patients:9 were followed for 1 ? 3 months(mean 2.4 months),and 1 patient was followed for 9 years before being diagnosed with prostate cancer. Two additional patients,whose pathological findings suggested a possible diagnosis of tuberculous granulomatous prostatitis,were advised to undergo anti-tuberculosis treatment at another hospital and were subsequently lost to follow-up. Among the 2 patients who underwent thulium laser enucleation,IPSS decreased from 26 and 25 to 6 and 5 respectively,QOL scores decreased from 6 and 5 to 1 and 0 respectively,Q max increased from 4.5 and 4.3 ml/s to 23.0 and 21.9 ml/s respectively. In the 8 patients treated conservatively,IPSS decreased from 18.45±7.17 to 14.45±5.03,and QOL score decreased from 5.09±1.04 to 4.09±0.70 at 1 month after treatment,showing significant improvement( P < 0.05). Additionally,one patient initially diagnosed with GP and managed conservatively remained stable for 9 years,but subsequently developed urinary retention and underwent thulium laser enucleation,with postoperative pathology confirming prostate cancer. Conclusions:Clinical manifestations of GP are nonspecific,and the condition can easily be mistaken for prostate cancer due to elevated PSA levels and PI-RADS scores ≥4. Some patients may present with acute urinary retention,but definitive diagnosis still relies on prostate biopsy and immunohistochemistry. Treatment should be individualized according to the underlying etiology,with medication as the mainstay,while transurethral surgical intervention may be considered in cases with obstruction. Although GP is a benign lesion,its potential association with prostate cancer warrants vigilance and emphasizes the importance of long-term follow-up.
7.Quality and Safety Evaluation of Antibacterial Agents in Aciclovir Eye Drops Based on National Drug Sampling and Testing
Weiwei JIA ; Weifeng DU ; Xinghong WEI ; Yi LIU ; Zili XIE
Herald of Medicine 2025;44(9):1400-1404
Objective To establish a high-throughput HPLC method for the simultaneous determination of 11 common antibacterial agents in acyclovir eye drops and to evaluate the quality and safety of the antibacterial agents in 42 batches of national drug inspection samples.Methods Gradient elution was performed on a Kromasil 100-5-C18(4.6 mm×250 mm,5 μm)column with acetonitrile-5 mmol·L-1 ammonium acetate aqueous solution(containing 1%triethylamine,pH adjusted to 4.5 by acetic acid)as the mobile phase.The detection wavelength was 262 nm.Results Good linear relationships were obtained for 11 antibacterial agents(r≥0.999 9).The average recovery range was 98.2%-101.8%,and the RSD was 0.7%-2.7%(n=9).As revealed by the systematic analysis of 42 batches of national drug inspection samples,some batches of samples were detected with out-of-prescription antibacterial agents 4-hydroxybenzoic acid and ethylparaben,and the results were 0.02-49 μg·mL-1.This indicated that ethylparaben degradation and colinear production pollution were the two major risk sources.Conclusions The method is accurate,sensitive,and specific and can be used for the qualitative and quantitative detection of antibacterial agents in acyclovir eye drops.Besides,some products have degradation of antibacterial agents and incomplete cleaning during co-linear production.It is still essential to further reinforce product quality control.
8.Clinicopathological analysis of 10 cases of diffuse pulmonary meningotheliomatosis
Shicui QUAN ; Nian WANG ; Zhiling XIE ; Qin LIU ; Qiong WANG ; Weifeng WEI ; Naijian LI ; Ping HE ; Jin-lin WANG
Chinese Journal of Clinical and Experimental Pathology 2025;41(9):1194-1199
Purpose This study aims to investigate the clinicopathological features of diffuse pulmonary menin-gotheliomatosis(DPM).Methods The clinical data of 10 patients with DPM undergoing video-assisted thoracic sur-gery(VATS)were collected,and their clinical and pathological characteristics were analyzed using immunohistochem-istry.Results The detection rate of DPM was 1.19‰,with 90%of the patients being female.DPM predominantly occurred in the age range of 40-60 years,with an average age at diagnosis of 50.7 years.Most patients had no smok-ing history.Pathological diagnosis combined with imaging findings was the main method for diagnosing DPM.80%of the patients were prone to concurrent early-stage invasive pulmonary adenocarcinoma.Laboratory indicators,including pulmonary function,were generally normal.Chest CT showed diffuse multiple ground-glass opacity or cystic nodules in both lungs,with the number of nodules in both lungs ranging from dozens to hundreds,and the maximum diameter of the nodules was 2-6 mm.The median volume and CT value of the pulmonary nodules were 35.32 mm3 and-566 HU,respectively.Pathological features mainly included multiple meningothelial-like nodules observed under the micro-scope.Immunophenotypically,CD56,EMA,PR,and vimentin were often positive.Conclusion DPM is a rare lung disease with no obvious clinical symptoms,and is more common in middle-aged and elderly women.Diffuse multiple nodules in both lungs are its main imaging features.Most DPM patients are complicated with lung adenocarcinoma,and regular follow-up is recommended.
9.Application value of optimized mesenteric defect closure technique in laparoscopic-assisted right hemicolectomy
Hengrui NIU ; Wenqing HU ; Peng CUI ; Yinhao YANG ; Jie WANG ; Dongyang SONG ; Weifeng LI ; Xiongxiong SONG ; Wei WEI
Chinese Journal of Digestive Surgery 2025;24(5):630-635
Objective:To investigate the application value of optimized mesenteric defect closure technique in laparoscopic-assisted right hemicolectomy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 26 patients who underwent laparo-scopic-assisted right hemicolectomy at Changzhi People′s Hospital Affiliated to Changzhi Medical College from May 2023 to June 2024 were collected. There were 11 males and 15 females, aged (65.7±1.8)years. All patients received optimized mesenteric defect closure using a combined extra-corporeal-laparoscopic suturing technique. Observation indicators: (1) surgical and intraoperative conditions; (2) postoperative conditions; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3) or M(range). Count data were described as absolute numbers. Results:(1) Surgical and intraoperative conditions. All 26 patients underwent laparoscopic-assisted right hemicolectomy with optimized mesenteric defect closure. The time of optimized mesenteric defect closure was 9.8(8.8,12.8)minutes, time of digestive tract reconstruction was 10.0(8.7,13.0)minutes, operation time was (164±4)minutes, volume of intraoperative blood loss was 50(50,100)mL. One of the 26 patients had intraoperative mesenteric hematoma, which required no specific intervention. The patient recovered uneventfully and was discharged from hospital. (2) Postoperative conditions. The visual analog scale pain score of 26 patients on postoperative day 1 and day 3 were 5(4,5) and 3(2,3), respectively. Time to postoperative first anal flatus and bowel movement were both 3(3, 4)days. Time to postoperative first intake of liquid diet was 2(2,3)days, duration of postoperative abdominal drainage was 4(3,5)days, and duration of postoperative hospital stay was 9(8,12)days. The number of lymph node dissected in 26 patients was 25(18,27) and the number of positive lymph node was 1(0,2). Cases in stage Ⅰ, stage Ⅱ and stage Ⅲ of tumor TNM staging were 5, 6, 15. (3) Follow-up. All 26 patients were followed up for 15(range, 6?20)months. Of the 26 patients, one case had incom-plete intestinal obstruction on postoperative day 25, which was diagnosed as adhesive intestinal obstruction based on imaging examination and classified as Clavien-Dindo grade Ⅱ. The patient recovered and was discharged after conservative treatment. None of the 26 patients had bleeding, infection of incision, anastomotic leakage, internal hernia, or delayed gastric emptying. There was no tumor recurrence, metastasis or death.Conclusion:The optimized mesenteric defect closure tech-nique in combined extracorporeal-laparoscopic suturing procedure can be used in laparoscopic-assisted right hemicolectomy.
10.Clinicopathological analysis of 10 cases of diffuse pulmonary meningotheliomatosis
Shicui QUAN ; Nian WANG ; Zhiling XIE ; Qin LIU ; Qiong WANG ; Weifeng WEI ; Naijian LI ; Ping HE ; Jin-lin WANG
Chinese Journal of Clinical and Experimental Pathology 2025;41(9):1194-1199
Purpose This study aims to investigate the clinicopathological features of diffuse pulmonary menin-gotheliomatosis(DPM).Methods The clinical data of 10 patients with DPM undergoing video-assisted thoracic sur-gery(VATS)were collected,and their clinical and pathological characteristics were analyzed using immunohistochem-istry.Results The detection rate of DPM was 1.19‰,with 90%of the patients being female.DPM predominantly occurred in the age range of 40-60 years,with an average age at diagnosis of 50.7 years.Most patients had no smok-ing history.Pathological diagnosis combined with imaging findings was the main method for diagnosing DPM.80%of the patients were prone to concurrent early-stage invasive pulmonary adenocarcinoma.Laboratory indicators,including pulmonary function,were generally normal.Chest CT showed diffuse multiple ground-glass opacity or cystic nodules in both lungs,with the number of nodules in both lungs ranging from dozens to hundreds,and the maximum diameter of the nodules was 2-6 mm.The median volume and CT value of the pulmonary nodules were 35.32 mm3 and-566 HU,respectively.Pathological features mainly included multiple meningothelial-like nodules observed under the micro-scope.Immunophenotypically,CD56,EMA,PR,and vimentin were often positive.Conclusion DPM is a rare lung disease with no obvious clinical symptoms,and is more common in middle-aged and elderly women.Diffuse multiple nodules in both lungs are its main imaging features.Most DPM patients are complicated with lung adenocarcinoma,and regular follow-up is recommended.

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