1.Recent advances in the application of three dimensional reconstruction techniques in surgical treatment of early lung cancer
Tao LONG ; Zhengbing REN ; Aizhong SHAO ; Zhicheng HE ; Weibing WU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(01):121-128
Lung cancer is the leading cause of death worldwide. With the prevalence of CT screening and early diagnosis and treatment of lung cancer in China, more and more patients with early-stage lung cancer characterized with ground-glass opacity are discovered and urgently require treatment, which poses a significant challenge to surgeons. As an emerging technology, three dimensional reconstruction technology plays a crucial auxiliary role in clinical work. This review aims to briefly introduce this technology, focusing on its latest advances in surgical applications in early lung cancer screening, malignant risk assessment, and perioperative period application and medical education.
2.Fibroblast activation protein targeting radiopharmaceuticals: From drug design to clinical translation.
Yuxuan WU ; Xingkai WANG ; Xiaona SUN ; Xin GAO ; Siqi ZHANG ; Jieting SHEN ; Hao TIAN ; Xueyao CHEN ; Hongyi HUANG ; Shuo JIANG ; Boyang ZHANG ; Yingzi ZHANG ; Minzi LU ; Hailong ZHANG ; Zhicheng SUN ; Ruping LIU ; Hong ZHANG ; Ming-Rong ZHANG ; Kuan HU ; Rui WANG
Acta Pharmaceutica Sinica B 2025;15(9):4511-4542
The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.
3.Alpha-synuclein Fibrils Inhibit Activation of the BDNF/ERK Signaling Loop in the mPFC to Induce Parkinson's Disease-like Alterations with Depression.
Zhuoran MA ; Yan XU ; Piaopiao LIAN ; Yi WU ; Ke LIU ; Zhaoyuan ZHANG ; Zhicheng TANG ; Xiaoman YANG ; Xuebing CAO
Neuroscience Bulletin 2025;41(6):951-969
Depression (Dep) is one of the most common concomitant symptoms of Parkinson's disease (PD), but there is a lack of detailed pathologic evidence for the occurrence of PD-Dep. Currently, the management of symptoms from both conditions using conventional pharmacological interventions remains a formidable task. In this study, we found impaired activation of extracellular signal-related kinase (ERK), reduced levels of transcription and translation, and decreased expression of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC) of PD-Dep rats. We demonstrated that the abnormal phosphorylation of α-synuclein (pS129) induced tropomyosin-related kinase receptor type B (TrkB) retention at the neuronal cell membrane, leading to BDNF/TrkB signaling dysfunction. We chose SEW2871 as an ameliorator to upregulate ERK phosphorylation. The results showed that PD-Dep rats exhibited improvement in behavioral manifestations of PD and depression. In addition, a reduction in pS129 was accompanied by a restoration of the function of the BDNF/ERK signaling loop in the mPFC of PD-Dep rats.
Animals
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Brain-Derived Neurotrophic Factor/metabolism*
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alpha-Synuclein/metabolism*
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Male
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Prefrontal Cortex/drug effects*
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Rats, Sprague-Dawley
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Depression/metabolism*
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MAP Kinase Signaling System/drug effects*
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Rats
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Parkinson Disease/metabolism*
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Receptor, trkB/metabolism*
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Phosphorylation
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Disease Models, Animal
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Signal Transduction
4.Human Cortical Organoids with a Novel SCN2A Variant Exhibit Hyperexcitability and Differential Responses to Anti-Seizure Compounds.
Yuling YANG ; Yang CAI ; Shuyang WANG ; Xiaoling WU ; Zhicheng SHAO ; Xin WANG ; Jing DING
Neuroscience Bulletin 2025;41(11):2010-2024
Mutations in ion channel genes have long been implicated in a spectrum of epilepsy syndromes. However, therapeutic decision-making is relatively complex for epilepsies associated with channelopathy. Therefore, in the present study, we used a patient-derived organoid model with a novel SCN2A mutation (p.E512K) to investigate the potential of utilizing such a model as a platform for preclinical testing of anti-seizure compounds. The electrophysiological properties of the variant Nav1.2 exhibited gain-of-function effects with increased current amplitude and premature activation. Immunofluorescence staining of patient-derived cortical organoids (COs) displayed normal neurodevelopment. Multielectrode array (MEA) recordings of patient-derived COs showed hyperexcitability with increased spiking and remarkable network bursts. Moreover, the application of patient-derived COs for preclinical drug testing using the MEA showed that they exhibit differential responses to various anti-seizure drugs and respond well to carbamazepine. Our results demonstrate that the individualized organoids have the potential to serve as a platform for preclinical pharmacological assessment.
Organoids/physiology*
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NAV1.2 Voltage-Gated Sodium Channel/genetics*
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Humans
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Anticonvulsants/pharmacology*
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Epilepsy/drug therapy*
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Mutation
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Cerebral Cortex/drug effects*
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Action Potentials/drug effects*
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Carbamazepine/pharmacology*
5.Current status and visual analysis of the burn-related sepsis.
Like ZHANG ; Wei YI ; Lijing ZHU ; Weibo XIE ; Zhicheng GU ; Guosheng WU ; Zhaofan XIA
Chinese Critical Care Medicine 2025;37(3):255-261
OBJECTIVE:
To explore the current status, evolution, hot topics, and future research trends in the field of burn-related sepsis research through a visual analysis of literature.
METHODS:
A bibliometric method was employed to retrieve articles related to burn-related sepsis from January 1, 1994, to May 16, 2024, in the China National Knowledge Infrastructure (CNKI) and the Web of Science database. The CiteSpace 6.3.R1 software was used to analyze the retrieved literature. The number of publications, authors, countries, and institutions in both Chinese and English literature was statistically analyzed. Co-occurrence analysis, clustering analysis, and co-citation analysis of keywords were performed.
RESULTS:
A total of 1 090 articles from the CNKI database and 1 143 articles from the Web of Science database were retrieved. Over the past 20 years, the volume of Chinese publications has remained stable, although there has been a slight decline in the past two years. In contrast, the number of English publications, after a period of growth, showed a sharp decline over the past three years. In Chinese literature, 1 457 authors published articles on burn-related sepsis as first authors, with 14 core authors publishing four or more articles. In English literature, 98 authors published articles on burn-related sepsis as first authors. Research on burn-related sepsis was conducted by 76 countries, with the United States having the most collaborations and publications. Globally, 1 349 institutions published articles on burn-related sepsis, with the top institutions being the First Affiliated Hospital of the PLA General Hospital (8 articles) for Chinese literature and the University of Texas Medical Branch (57 articles) for English literature. In the co-occurrence analysis, 208 Chinese keywords and 211 English keywords were included. Excluding keywords related to search terms, the top five most frequent keywords in Chinese literature were burn, sepsis, infection, severe burn, and procalcitonin; the top five most frequent keywords in English literature were sepsis, septic shock, mortality, injury, and burn injury. Chinese keyword analysis identified six clusters, with the largest being sepsis, followed by procalcitonin, infection, and severe burn. English keyword analysis identified seven clusters, with the largest being expression, followed by epidemiology, inhalation injury, and acute kidney injury. The persistent clusters in Chinese literature were procalcitonin, with recent emerging nodes being severe burn, inflammatory response, platelets, and predictive value. In English literature, the persistent clusters were inhalation injury and nitric oxide, with recent emerging nodes being continuous renal replacement therapy, hemorrhagic shock, and early enteral nutrition. The longest-lasting emergent keyword in Chinese literature was delayed resuscitation (2003-2010), with the highest emergent strength being severe burn. In English literature, the longest-lasting emergent keywords, each lasting five years, were nitric oxide (2007-2012), management (2019-2024), and impact (2019-2024), with the highest emergent strength being thermal injury.
CONCLUSIONS
Research on burn-related sepsis has shifted from focusing on early studies on pathogenesis and mortality to focus on prevention, treatment, and early diagnosis. Future research is expected to focus on early diagnosis and risk factors of burn-related sepsis.
Burns/complications*
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Sepsis/etiology*
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Humans
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Bibliometrics
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China
6.Recent advances in platelet lipid rafts
Diyang WU ; Lujie ZHOU ; Zhicheng WANG
Chinese Journal of Blood Transfusion 2025;38(10):1421-1426
Platelet lipid rafts are dynamic nanodomains enriched in cholesterol and sphingolipids within the plasma membrane. As pivotal hubs for signal transduction, membrane trafficking, and intercellular interactions, they have garnered significant attention in recent years for their roles in regulating platelet function and related disease mechanisms. This article reviews the structural characteristics and molecular composition of platelet lipid rafts, as well as their central roles in signal transduction and cytoskeletal reorganization. It particularly focuses on the functional abnormalities and pathological contributions of lipid rafts in diseases such as atherosclerosis, antiphospholipid antibody syndrome, and ANCA-associated vasculitis. Research indicates that lipid rafts coordinate platelet activation, inflammatory responses, and immunomodulatory processes by integrating receptor clustering, enrichment of signaling proteins, and regulation of metabolites. Finally, the article discusses the future prospects of lipid raft-targeted nanotherapeutic strategies and addresses challenges in translational research, providing a theoretical foundation and novel perspectives for understanding platelet biology and intervening in thrombo-inflammatory diseases.
7.Impact of the Size and Depth of Pulmonary Nodules on the Surgical Approach for Lung Resection in the Treatment of Early-stage Lung Cancer ≤2 cm
TANG ZAIBIN ; GE WENKE ; ZHOU DINGYE ; HE ZHICHENG ; XU JING ; PAN XIANGLONG ; CHEN LIANG ; WU WEIBING
Chinese Journal of Lung Cancer 2024;27(3):170-178
Background and objective Current studies suggest that for early-stage lung cancers with a component of ground-glass opacity measuring ≤2 cm,sublobar resection is suitable if it ensures adequate margins.However,lobectomy may be necessary for some cases to achieve this.The aim of this study was to explore the impact of size and depth on surgical techniques for wedge resection,segmentectomy,and lobectomy in early-stage lung cancer ≤2 cm,and to determine methods for ensuring a safe resection margin during sublobar resections.Methods Clinical data from 385 patients with early-stage lung can-cer ≤2 cm,who underwent lung resection in 2022,were subject to a retrospective analysis,covering three types of procedures:wedge resection,segmentectomy and lobectomy.The depth indicator as the OA value,which is the shortest distance from the inner edge of a pulmonary nodule to the opening of the corresponding bronchus,and the AB value,which is the distance from the inner edge of the nodule to the pleura,were measured.For cases undergoing lobectomy and segmentectomy,three-dimensional computed tomography bronchography and angiography(3D-CTBA)was performed to statistically determine the number of subsegments required for segmentectomy.The cutting margin width for wedge resection and segmentectomy was recorded,as well as the specific subsegments and their quantities removed during lung segmentectomy were documented.Results In wedge resection,segmentectomy,and lobectomy,the sizes of pulmonary nodules were(1.08±0.29)cm,(1.31±0.34)cm and(1.50±0.35)cm,respectively,while the depth of the nodules(OA values)was 6.05(5.26,6.85)cm,4.43(3.27,5.43)cm and 3.04(1.80,4.18)cm for each procedure,showing a progressive increasing trend(P<0.001).The median resec-tion margin width obtained from segmentectomy was 2.50(1.50,3.00)cm,significantly greater than the 1.50(1.15,2.00)cm from wedge resection(P<0.001).In wedge resections,cases where AB value>2 cm demonstrated a higher proportion of cases with resection margins less than 2 cm compared to those with margins greater than 2 cm(29.03%vs 12.90%,P=0.019).When utilizing the size of the nodule as the criterion for resection margin,the instances with AB value>2 cm continued to show a higher proportion in the ratio of margin distance to tumor size less than 1(37.50%vs 17.39%,P=0.009).The median number of subsegments for segmentectomy was three,whereas lobectomy cases requiring segmentectomy involved five subsegments(P<0.001).Conclusion The selection of the surgical approach for lung resection is influenced by both the size and depth of pulmonary nodules.This study first confirms that larger portions of lung tissue must be removed for nodules that are deeper and larger to achieve a safe margin.A distance of ≤2 cm from the inner edge of the pulmonary nodule to the nearest pleura may be the ideal indication for performing wedge resection.
8.Vaccination against coronavirus disease 2019 in patients with pulmonary hypertension: A national prospective cohort study
Xiaohan WU ; Jingyi LI ; Jieling MA ; Qianqian LIU ; Lan WANG ; Yongjian ZHU ; Yue CUI ; Anyi WANG ; Cenjin WEN ; Luhong QIU ; Yinjian YANG ; Dan LU ; Xiqi XU ; Xijie ZHU ; Chunyan CHENG ; Duolao WANG ; Zhicheng JING
Chinese Medical Journal 2024;137(6):669-675
Background::Coronavirus disease 2019 (COVID-19) has potential risks for both clinically worsening pulmonary hypertension (PH) and increasing mortality. However, the data regarding the protective role of vaccination in this population are still lacking. This study aimed to assess the safety of approved vaccination for patients with PH.Methods::In this national prospective cohort study, patients diagnosed with PH (World Health Organization [WHO] groups 1 and 4) were enrolled from October 2021 to April 2022. The primary outcome was the composite of PH-related major adverse events. We used an inverse probability weighting (IPW) approach to control for possible confounding factors in the baseline characteristics of patients.Results::In total, 706 patients with PH participated in this study (mean age, 40.3 years; mean duration after diagnosis of PH, 8.2 years). All patients received standardized treatment for PH in accordance with guidelines for the diagnosis and treatment of PH in China. Among them, 278 patients did not receive vaccination, whereas 428 patients completed the vaccination series. None of the participants were infected with COVID-19 during our study period. Overall, 398 patients received inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, whereas 30 received recombinant protein subunit vaccine. After adjusting for baseline covariates using the IPW approach, the odds of any adverse events due to PH in the vaccinated group did not statistically significantly increase (27/428 [6.3%] vs. 24/278 [8.6%], odds ratio = 0.72, P = 0.302). Approximately half of the vaccinated patients reported at least one post-vaccination side effects, most of which were mild, including pain at the injection site (159/428, 37.1%), fever (11/428, 2.6%), and fatigue (26/428, 6.1%). Conclusions::COVID-19 vaccination did not significantly augment the PH-related major adverse events for patients with WHO groups 1 and 4 PH, although there were some tolerable side effects. A large-scale randomized controlled trial is warranted to confirm this finding. The final approval of the COVID-19 vaccination for patients with PH as a public health strategy is promising.
9.The switch triggering the invasion process: Lipid metabolism in the metastasis of hepatocellular carcinoma
Jiaqian ZHANG ; Zhicheng ZHANG ; Zhangfan WU ; Yufei WANG ; Zerui ZHANG ; Limin XIA
Chinese Medical Journal 2024;137(11):1271-1284
In humans, the liver is a central metabolic organ with a complex and unique histological microenvironment. Hepatocellular carcinoma (HCC), which is a highly aggressive disease with a poor prognosis, accounts for most cases of primary liver cancer. As an emerging hallmark of cancers, metabolic reprogramming acts as a runaway mechanism that disrupts homeostasis of the affected organs, including the liver. Specifically, rewiring of the liver metabolic microenvironment, including lipid metabolism, is driven by HCC cells, propelling the phenotypes of HCC cells, including dissemination, invasion, and even metastasis in return. The resulting formation of this vicious loop facilitates various malignant behaviors of HCC further. However, few articles have comprehensively summarized lipid reprogramming in HCC metastasis. Here, we have reviewed the general situation of the liver microenvironment and the physiological lipid metabolism in the liver, and highlighted the effects of different aspects of lipid metabolism on HCC metastasis to explore the underlying mechanisms. In addition, we have recapitulated promising therapeutic strategies targeting lipid metabolism and the effects of lipid metabolic reprogramming on the efficacy of HCC systematical therapy, aiming to offer new perspectives for targeted therapy.
10.Association between coronary artery stenosis and myocardial injury in patients with acute pulmonary embolism: A case-control study
Yinjian YANG ; Chao LIU ; Jieling MA ; Xijie ZHU ; Jingsi MA ; Dan LU ; Xinxin YAN ; Xuan GAO ; Jia WANG ; Liting WANG ; Sijin ZHANG ; Xianmei LI ; Bingxiang WU ; Kai SUN ; Yimin MAO ; Xiqi XU ; Tianyu LIAN ; Chunyan CHENG ; Zhicheng JING
Chinese Medical Journal 2024;137(16):1965-1972
Background::The potential impact of pre-existing coronary artery stenosis (CAS) on acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and the elevation of high-sensitivity cardiac troponin I (hs-cTnI) levels in patients with PE.Methods::In this multicenter, prospective case-control study, 88 cases and 163 controls matched for age, sex, and study center were enrolled. Cases were patients with PE with elevated hs-cTnI. Controls were patients with PE with normal hs-cTnI. Coronary artery assessment utilized coronary computed tomographic angiography or invasive coronary angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression was used to evaluate the association between CAS and hs-cTnI elevation.Results::The percentage of CAS was higher in the case group compared to the control group (44.3% [39/88] vs. 30.1% [49/163]; P = 0.024). In multivariable conditional logistic regression model 1, CAS (adjusted odds ratio [OR], 2.680; 95% confidence interval [CI], 1.243–5.779), heart rate >75 beats/min (OR, 2.306; 95% CI, 1.056–5.036) and N-terminal pro-B type natriuretic peptide (NT-proBNP) >420 pg/mL (OR, 12.169; 95% CI, 4.792–30.900) were independently associated with elevated hs-cTnI. In model 2, right CAS (OR, 3.615; 95% CI, 1.467–8.909) and NT-proBNP >420 pg/mL (OR, 13.890; 95% CI, 5.288–36.484) were independently associated with elevated hs-cTnI. Conclusions::CAS was independently associated with myocardial injury in patients with PE. Vigilance towards CAS is warranted in patients with PE with elevated cardiac troponin levels.

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