BACKGROUND: The proportion of patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations is relatively high in China. However, these patients currently lack significant benefits from available neoadjuvant treatment options. This study aims to explore the potential application value of neoadjuvant targeted therapy by evaluating its efficacy and safety in patients with EGFR-mutant resectable lung adenocarcinoma. METHODS: A multicenter retrospective study was used to analyze the treatment effect of patients with stage IIA-IIIB EGFR-mutant lung adenocarcinoma who underwent surgical resection after receiving neoadjuvant targeted therapy from July 2019 to October 2024. RESULTS: A total of 24 patients with EGFR-mutant lung adenocarcinoma from three centers were included in this study. All patients successfully underwent surgery and achieved R0 resection of 100.0%. The objective response rate (ORR) was 83.3% (20/24) . The major pathologic response (MPR) rate was 37.5% (9/24), with 2 patients (8.3%) achieving pathological complete response (pCR). During neoadjuvant therapy, 13 out of 24 patients (54.2%) experienced adverse events of grade 1-2, with no occurrences of ≥ grade 3. The most common treatment-related adverse events were rash (n=4, 16.7%), mouth sores (n=2, 8.3%), and diarrhea (n=2, 8.3%). The median follow-up time was 33.0 months, no deaths occurred in all patients, and the overall survival (OS) rate was 100.0%. The 1-year disease-free survival (DFS) rate was 91.1%, and the 2-year DFS rate remained at 86.2%. CONCLUSIONS The application of neoadjuvant targeted therapy in patients with EGFR-mutant resectable lung adenocarcinoma is safe and feasible, and is expected to become a highly promising neoadjuvant treatment option for the patients with EGFR-mutant lung adenocarcinoma.
Humans ; ErbB Receptors/metabolism* ; Male ; Female ; Middle Aged ; Adenocarcinoma of Lung/surgery* ; Neoadjuvant Therapy ; Lung Neoplasms/surgery* ; Aged ; Retrospective Studies ; Mutation ; Adult

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.

Astragali Radix (AR) and Notoginseng Radix et Rhizoma (NR) are frequently employed in cardiovascular disease treatment. However, the efficacy of the AR-NR medicine pair (AN) in improving cardiac remodeling and its underlying mechanism remains unclear. This study aimed to evaluate AN's cardioprotective effect and potential mechanism on cardiac remodeling using transverse aortic constriction (TAC) in mice and angiotensin II (Ang II)-induced neonatal rat cardiomyocytes (NRCMs) and fibroblasts in vitro. High-performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (HPLC-Q-TOF-MS/MS) characterized 23 main components of AN. AN significantly improved cardiac function in the TAC-induced mice. Furthermore, AN considerably reduced the serum levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac troponin T (CTn-T), and interleukin-6 (IL-6) and mitigated inflammatory cell infiltration. Post-AN treatment, TAC-induced heart size approached normal. AN decreased cardiomyocyte cross-sectional area and attenuated the upregulation of cardiac hypertrophy marker genes (ANP, BNP, and MYH7) in vivo and in vitro. Concurrently, AN alleviated collagen deposition in TAC-induced mice. AN also reduced the expression of fibrosis-related indicators (COL1A1 and COL3A1) and inhibited the activation of the transforming growth factor-β1 (TGF-β1)/mothers against decapentaplegic homolog 3 (Smad3) pathway. Thus, AN improved TAC-induced cardiac remodeling. Moreover, AN downregulated p-dynamin-related protein (Drp1) (Ser616) expression and upregulated mitogen 2 (MFN-2) and optic atrophy 1 (OPA1) expression in vivo and in vitro, thereby restoring mitochondrial fusion and fission balance. In conclusion, AN improves cardiac remodeling by regulating mitochondrial dynamic balance, providing experimental data for the rational application of Chinese medicine prescriptions with AN as the main component in clinical practice.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Myocytes, Cardiac/metabolism* ; Mice ; Rats ; Male ; Mitochondrial Dynamics/drug effects* ; Ventricular Remodeling/drug effects* ; Astragalus Plant/chemistry* ; Mice, Inbred C57BL ; Rhizome/chemistry* ; Panax notoginseng/chemistry* ; Rats, Sprague-Dawley ; Natriuretic Peptide, Brain/genetics* ; Humans ; Angiotensin II ; Astragalus propinquus

Vascular remodeling is a physiological and pathological process in which abnormal changes in vas-cular cells and non-cellular components lead to the remodeling of inward and outward blood vessel wall or changes in lu-men diameter.As the channels for blood flow,blood vessels are continuously affected by hemodynamic forces.When sens-ing the abnormal blood flow forces,the mechanically sensitive cell membrane structures such as G protein-coupled recep-tors,ion channels,cell surface glycocalyx,and integrins,as well as the extracellular matrix will induce the process of vas-cular endothelial dysfunction,endothelial-mesenchymal transition,smooth muscle cell phenotypic switching,pericyte morphological changes and extracellular matrix remodeling to participate in vascular remodeling.As shown by research,abnormal hemodynamics caused abnormal changes in vascular structure and function,which was the basic process for the occurrence and development of pan-vascular diseases such as atherosclerosis,hypertension,diabetes,non-alcoholic fatty liver disease,pulmonary hypertension and COVID-19.This paper reviewed the interaction and molecular mechanism be-tween abnormal hemodynamics and vascular remodeling,and analyzed its influence on the pathogenesis of pan-vascular diseases,which could provide reference for formulating prevention and treatment strategies for pan-vascular diseases.

Objective:To explore the medication law of TCM compounds used in the treatment of non-small cell lung cancer (NSCLC).Methods:Clinical literature about TCM compounds in the treatment of NSCLC was retrieved from CNKI, Wanfang Data, PubMed and Web of Science core collection database from January 1st, 2003 to May 1st, 2023. The Python and the ancient and modern medical record cloud platform V2.3.7 were used to analyses frequency statistics and properties, and clustering analysis, factor analysis and association rule analysis were performed.Results:A total of 866 articles were included, with 660 effective TCM compounds, 647 kinds of Chinese materia medica. There were 36 kinds of high-frequency Chinese materia medica, such as Astragali Radix, Atractylodis Macrocephalae Rhizoma and Poria; the efficacy categories of Chinese materia medica mainly included tonics and phlegm resolving cough relieving and asthma relieving drugs. Cluster analysis obtained 4 clusters, factor analysis extracted 11 common factors, and association rule analysis obtained 37 highly supported combinations of Chinese materia medica. The most reliable triple drug combination among them was Astragali Radix-Atractylodis Macrocephalae Rhizoma-Hedyotis diffusa willd, and the double drug combination was Astragali Radix-Ligustri Lucidi Fructus.Conclusion:TCM for the treatment of NSCLC mainly focuses on strengthening the healthy qi, clearing heat, resolving phlegm and detoxifying toxins, supplemented by tonifying qi and activating blood circulation, dispelling dampness and resolving phlegm.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals ; Mice ; Methylation ; Chromatin ; Histones/metabolism* ; RNA, Messenger/genetics* ; Methyltransferases/metabolism* ; RNA/metabolism*

OBJECTIVE To investigate the intervention effects and potential mechanism of Miao medicine Toddalia asiatica on cardiovascular damage in rats with collagen-induced arthritis （CIA） based on vitamin D （VD） and neutrophil extracellular traps （NETs）. METHODS SD rats were randomly divided into the normal group （9 rats） and the modeling group （61 rats）. CIA model was prepared by multi-point injection of type Ⅱ bovine collagen+Fisher’s incomplete adjuvant； the model rats were randomly divided into the model group， methotrexate group （positive control， 1.5 mg/kg， twice a week）， vitamin D group [pathway validation， 1 000 IU/（kg·d）， once a day]， T. asiatica low-dose， medium-dose and high-dose groups [0.54， 1.08， 2.16 g/（kg·d）， calculated by crude drug， once a day]， with 9 rats in each group； they were given relevant medicine intragastrically for 4 consecutive weeks. Arthritis index scoring was performed after modeling and before administration， and plantar thickness was measured before and after the last administration； the histopathological changes of ankle joint， heart and abdominal aorta were observed in rats； the serum contents of myeloperoxidase （MPO）， interleukin-6 （IL-6） and 25-hydroxyvitamin D3 [25（OH）D3] were detected； the expressions of peptidylarginine deiminase 4 （PAD4）， NETs markers [citrullinated histone H3（CitH3）， MPO]， VD-related indicators [vitamin D receptor （VDR）， 25-hydroxyvitamin D-1α-hydroxylase （CYP27B1）] and IL-6 were determined in cardiac tissue. RESULTS Compared with the normal group， the plantar thickness of the arthritis index increased significantly in the model group （P＜0.01）. The obvious inflammatory cell infiltration and fibrous tissue hyperplasia were found in the ankle joint， the obvious myocardial fiber （No.2019YFC171250101） vacuoles and thickening of some surrounding blood vessel walls were found in the heart tissue， and the endothelial detachment was found in the abdominal aorta. The contents of MPO and IL-6 in serum increased significantly（P＜0.01），while the level of 25（OH）D3 decreased significantly （P＜0.01）； the protein expressions of PAD4， CitH3， MPO and IL-6 in myocardial tissue up-regulated significantly （P＜0.01）， while protein expression of VDR and CYP27B1 changed to acertain extent without significance （P＞0.05）. Compared with the model group， the pathological changes of ankle joints and cardiac tissue in rats were significantly improved in administration groups， and the above indicators were generally reversed （P＜0.05 or P＜0.01）. CONCLUSIONS T. asiatica can improve rheumatoid arthritis symptoms and cardiovascular damage by inhibiting the formation of NETs and inflammatory response， the mechanism of which may be associated with the regulation of VD expression.

In deep inferior epigastric perforator (DIEP) flap breast reconstruction, diffuse venous congestion caused by non-pedicle causes, such as lack of effective communication between deep and superficial venous systems, is very rare. In this paper, a case of young woman who underwent DIEP breast reconstruction after breast cancer mastectomy was reported. Imaging findings showed the absence of bilateral dominant perforators and the lack of communication between the deep and superficial venous system. During operation, the superficial inferior epigastric vessels were dissected in advance. Indocyanine green angiography showed arterial perfusion insufficiency and venous congestion.The flap was successfully salvaged by supercharging/draining with superficial inferior epigastric vessels, preserving the abdominal function of the young patient to the greatest extent.

Objective:This study aimed to explore the clinical application value of the indication selection criteria for bi-pedicled deep inferior epigastric arterial perforator flap(DIEP) versus pedicled transverse rectus abdominis myocutaneous flap(TRAM) combined with DIEP for breast reconstruction.Methods:The clinical data of patients who underwent delayed bi-pedicled abdominal flap breast reconstruction after breast cancer surgery in the Department of Oncoplastic and Reconstructive Breast Surgery and Department of Mammoplasty, Plastic Surgery Hospital, Chinese Academy of Medical Sciences from January 2008 to April 2022 were retrospectively analyzed. According to the indications for each procedure, corresponding blood supply source was selected. Subsequently, patients were divided into two groups: bi-pedicled DIEP group and pedicled TRAM+ DIEP combined flap group according to the type of blood supply source. The indication selection criteria for pedicled TRAM+ DIEP combined flap was as follows: lack of two groups of recipient vessels; no dominant perforator in the abdominal donor site; previous abdominal liposuction or abdominal surgery with large dissection range and severe scar; patients were unable to tolerate prolonged surgery or had high risk factors for microsurgery. A comparison of breast reconstruction surgery characteristics was conducted between the two groups. Independent-samples t-test, rank sum test, Chi-square test and Fisher’s exact probability method were used to analyze various data including age, body mass index (BMI), time interval between breast cancer surgery and breast reconstruction surgery, history of radiotherapy, history of chemotherapy, history of smoking, history of lower abdominal surgery, history of hypertension, original surgical incision type, length and width of flap, hospitalization length, preoperative and postoperative conditions, as well as postoperative complications. Statistical significance was defined at P<0.05. Results:A total of 54 patients who underwent unilateral breast reconstruction were included in this study with a mean age of 42.2 years (range, 30-59 years). The pedicled TRAM+ DIEP combined flap group consisted of 21 patients with a mean age of 42.7 years (range, 33-56 years) while the bi-pedicled DIEP group comprised 33 patients with a mean age of 41.8 years (30-59 years). Out of the 54 patients, a total of 38 were eventually followed up, comprising 14 in the pedicled TRAM+ DIEP combined flap group and 24 in the bi-pedicled DIEP group. The average follow-up duration for the pedicled TRAM+ DIEP combined flap group was 42 months (range, 6-69 months). Abdominal bulge occurred in one patient, while another patient experienced abdominal hernia. The average follow-up duration for the bi-pedicled DIEP group was 47 months (6-179 months), with no reported cases of abdominal bulge or abdominal hernia. There were no statistically significant differences observed between the two groups regarding age, BMI, time interval between breast cancer surgery and breast reconstruction surgery, history of radiotherapy or chemotherapy, history of smoking, history of lower abdominal surgery, history of hypertension, original surgical incision type, length and width of flap, hospitalization length or time to ambulation (all P>0.05). However, there was a statistically significant difference noted in duration of surgery between the pedicled TRAM+ DIEP combined flap group and bi-pedicled DIEP group [6.0(5.5-6.5) hours vs. 8.5(8.0-8.8) hours] ( P<0.01). Comparison analysis revealed no statistically significant differences in terms of partial flap necrosis (0/21 vs. 1/33), abdominal incision dehiscence (2/21 vs. 2/33), abdominal bulge (1/14 vs. 0 /24) or abdominal hernia (1/1 vs. 0/24) between the two groups ( P>0.05). Conclusion:For patients who needed bilateral vascular pedicled lower abdominal wall for breast reconstruction, utilizing a pedicled TRAM+ DIEP combined flap did not increase surgical complication risks. The proposed indication selection criteria for using a pedicled TRAM + DIEP combined flap outlined in this study could serve as guidance when choosing methods for bi-pedicled abdominal flap breast reconstruction.