Ground-glass nodules (GGNs) are common imaging manifestation in the early screening of lung adenocarcinoma. With the widespread use of low-dose computed tomography (LDCT) in lung cancer screening, the detection rate of GGNs has significantly increased. According to the presence or absence of a solid component, GGNs are mainly classified into pure ground-glass nodules (pGGNs) and mixed ground-glassnodules (mGGNs), which differ in their natural course and biological behavior. In general, pGGNs tend to progress more slowly, whereas mGGNs are more likely to develop invasive features. The vast majority of pGGNs remain stable for years, but some pGGNs and mGGNs may show an increase in size or in the solid component. The "indolence" observed on the surface of GGNs hides complex genomic, metabolic, and immune changes, which are difficult to capture with traditional image-based data. In recent years, multi-omics analysis, radiomics, and artificial intelligence models have provided new tools for identifying high-risk GGNs. However, there is still controversy over the clinical generalizability, interpretability, and standardization of these models. Furthermore, there is no consensus on whether surgical resection is required. This article reviews the molecular mechanisms, metabolic, and immune microenvironment changes involved in the progression of GGNs, discusses the advantages and limitations of imaging prediction models, and combines domestic and international guidelines and survival studies to explore the controversial points in follow-up and surgical strategies, aiming to provide references for the personalized management of GGNs.

Objective: To analyze the epidemiological characteristics, etiological distribution and risk factors of recurrent hand, foot and mouth disease (HFMD) in Jiaxing City, so as to provide scientific evidence for developing targeted prevention and control strategies. Methods: Based on the China Disease Prevention and Control Information System, data of all reported HFMD cases in Jiaxing City from January 1, 2016 to December 31, 2024 were collected. Epidemiological and etiological distribution characteristics of recurrent HFMD cases were described. The Kaplan-Meier method was applied to estimate the cumulative risk probability of reinfection, and the Cox proportional hazards regression model was used to identify risk factors for HFMD reinfection. Results: A total of 3 105 recurrent HFMD cases were reported in Jiaxing City during 2016-2024, with a reinfection rate of 3.99%. The majority of reinfections were second episodes (97.68%). HFMD reinfection was associated with sex, age, population category and etiological serotype ( χ 2=26.44, 609.92, 459.72, 32.01, all P <0.01). The incidence of recurrent HFMD exhibited a bimodal seasonal pattern, with peaks occurring from June to July and September to November. Spatial distribution indicated that Nanhu District, Jiashan County and Tongxiang City accounted for 49.02% of all recurrent cases citywide. Among 264 laboratory confirmed recurrent cases, EV-A71 was the predominant pathogen (29.92%). The proportion of EV-A71 showed a trend of initial decline followed by rebound, while the proportion of CV-A6 increased over time ( χ 2 trend =6.94, 47.43, both P <0.05). Of 51 patients with ≥2 etiological test results, 56.86 % experienced reinfection with a different serotype. The median time to HFMD reinfection was 17.23 (0.50, 105.03) months after the primary episode. The reinfection probability was 0.61% at 6 months, 3.68% at 36 months, and remained approximately 5% at 64.37 months. Multivariate Cox regression revealed that male sex ( HR =1.23), age ≤ 3 years ( HR = 1.84), and scattered children and preschool children ( HR =3.78, 3.47, respectively) were independent risk factors for HFMD reinfection (all P <0.05). Conclusions Recurrent HFMD in Jiaxing City presents temporal and population heterogeneity, and its etiology shows an alternating serotype evolution pattern. Enhanced surveillance should be implemented among priority populations and high incidence regions, and multivalent vaccines should be developed to confer broader protection.

Background: Inhalation-based combination therapy has gained increasing attention for local treatments. However, a key challenge remains in ensuring the sustained pulmonary release of multiple active ingredients, particularly in traditional Chinese medicine (TCM) formulations. Objective: This study investigates a novel PulmoSphere-based inhalable carrier designed for the sustained pulmonary release of multiple active ingredients, using Shuang-Huang-Lian as a model TCM formulation containing three chemical markers. Materials and methods: The carrier was developed using PulmoSphere technology, incorporating phospholipid complexes of the chemical markers and hyaluronic acid (HA) into spray-dried microparticles. The aerodynamic properties, release characteristics, pulmonary distribution, and anti-inflammatory efficacy of different formulations were evaluated in vitro and in mice. Results: The microparticles retained the excellent aerodynamic properties of conventional PulmoSphere particles, with a mass median aerodynamic diameter of approximately 3.1 μm and a fine particle fraction of approximately 55%. Compared to free Shuang-Huang-Lian or phospholipid complex-loaded PulmoSphere particles, the HA-containing particles prolonged the retention of chemical markers in the lung epithelial lining fluid, demonstrating sustained release in vivo. Additionally, the HA-containing formulation enhanced the exposure of the three chemical markers to immune cells and lung tissues, leading to improved and prolonged anti-inflammatory effects, even at decreased doses. Conclusion: This novel inhalable particle system represents a promising approach for sustained pulmonary co-delivery of multiple active ingredients, offering enhanced and extended local therapeutic efficacy.

PURPOSE: Assessing fluid responsiveness relying on central venous oxygen saturation (ScvO₂) yields varied outcomes across several studies. This study aimed to determine the ability of the change in ScvO₂ (ΔScvO₂) to detect fluid responsiveness in ventilated septic shock patients and potential influencing factors. METHODS: In this prospective, single-center study, all patients conducted from February 2023 to January 2024 received fluid challenge. Oxygen consumption was measured by indirect calorimetry, and fluid responsiveness was defined as an increase in cardiac index (CI) ≥ 10% measured by transthoracic echocardiography. Multivariate linear regression analysis was conducted to evaluate the impact of oxygen consumption, arterial oxygen saturation, CI, and hemoglobin on ScvO₂ and its change before and after fluid challenge. The Shapiro-Wilk test was used for the normality of continuous data. Data comparison between fluid responders and non-responders was conducted using a two-tailed Student t-test, Mann Whitney U test, and Chi-square test. Paired t-tests were used for normally distributed data, while the Wilcoxon signed-rank test was used for skewed data, to compare data before and after fluid challenge. RESULTS: Among 49 patients (31 men, aged (59 ± 18) years), 27 were responders. The patients had an acute physiology and chronic health evaluation II score of 24 ± 8, a sequential organ failure assessment score of 11 ± 4, and a blood lactate level of (3.2 ± 3.1) mmol/L at enrollment. After the fluid challenge, the ΔScvO₂ (mmHg) in the responders was greater than that in the non-responders (4 ± 6 vs. 1 ± 3, p = 0.019). Multivariate linear regression analysis suggested that CI was the only independent influencing factor of ScvO₂, with R² = 0.063, p = 0.008. After the fluid challenge, the change in CI became the only contributing factor to ΔScvO₂ (R² = 0.245, p < 0.001). ΔScvO₂ had a good discriminatory ability for the responders and non-responders with a threshold of 4.4% (area under the curve = 0.732, p = 0.006). CONCLUSION ΔScvO₂ served as a reliable surrogate marker for ΔCI and could be utilized to assess fluid responsiveness, given that the change in CI was the sole contributing factor to the ΔScvO₂. In stable hemoglobin conditions, the absolute value of ScvO₂ could serve as a monitoring indicator for adequate oxygen delivery independent of oxygen consumption.
Humans ; Shock, Septic/blood* ; Male ; Female ; Middle Aged ; Prospective Studies ; Oxygen Saturation ; Aged ; Fluid Therapy ; Oxygen/blood* ; Oxygen Consumption ; Adult

OBJECTIVES: To investigate the medium- and long-term efficacy of percutaneous mechanical thrombectomy (PMT) combined with stent implantation for treatment of iliac vein stenosis with lower extremity deep venous thrombosis (LEDVT). METHODS: Clinical and follow-up data of 125 patients with iliac vein stenosis and LEDVT who underwent PMT and stent implantation at five hospitals in northern Zhejiang province from January 2017 to June 2021 were collected. The thrombus clearance rate, thrombus recurrence rate, patency rate of iliac vein stents and post-thrombotic syndrome (PTS) occurrence rate were documented, and safety indicators such as bleeding, death, pulmonary embolism, stent fracture and displacement were assessed. RESULTS: Among 125 patients, for clearance of limb thrombosis, there were 8 cases of grade I (6.4%), 10 cases of grade II (8.0%), and 107 cases of grade III (85.6%). Patients were followed up for a median period of 74 months. According to the Villalta score, the recurrence rates of limb thrombosis at 12, 24 and 36 months were 8.48%, 8.93% and 10.91%; the iliac vein patency rates were 91.52%, 91.07%, and 89.09%; and the incidences of PTS were 5.08%, 5.36% and 6.36%, respectively. There were no major adverse events such as death, massive pulmonary embolism or severe hepatic and renal insufficiency, and no readmission intervention events due to stent fracture or other incidence were found. CONCLUSIONS PMT combined with iliac vein stent implantation is effective for patients with iliac vein stenosis complicated by LEDVT with good medium- and long-term efficacy and safety, which is worthy of clinical application.
Humans ; Stents ; Iliac Vein/pathology* ; Venous Thrombosis/surgery* ; Thrombectomy/methods* ; Female ; Male ; Middle Aged ; Aged ; Adult ; Constriction, Pathologic/surgery* ; Treatment Outcome ; Follow-Up Studies

Network pharmacology has gained widespread application in drug discovery, particularly in traditional Chinese medicine (TCM) research, which is characterized by its "multi-component, multi-target, and multi-pathway" nature. Through the integration of network biology, TCM network pharmacology enables systematic evaluation of therapeutic efficacy and detailed elucidation of action mechanisms, establishing a novel research paradigm for TCM modernization. The rapid advancement of machine learning, particularly revolutionary deep learning methods, has substantially enhanced artificial intelligence (AI) technology, offering significant potential to advance TCM network pharmacology research. This paper describes the methodology of TCM network pharmacology, encompassing ingredient identification, network construction, network analysis, and experimental validation. Furthermore, it summarizes key strategies for constructing various networks and analyzing constructed networks using AI methods. Finally, it addresses challenges and future directions regarding cell-cell communication (CCC)-based network construction, analysis, and validation, providing valuable insights for TCM network pharmacology.
Medicine, Chinese Traditional/methods* ; Artificial Intelligence ; Network Pharmacology/methods* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Drug Discovery

Food-derived bioactive peptides (FBPs), particularly those with ten or fewer amino acid residues and a molecular weight below 1300 Da, have gained increasing attention for their safe, diverse structures and specific biological activities. The development of FBP-based functional foods and potential medications depends on understanding their structure‒activity relationships (SARs), stability, and bioavailability properties. In this review, we provide an in-depth overview of the roles of FBPs in treating various diseases, including Alzheimer's disease, hypertension, type 2 diabetes mellitus, liver diseases, and inflammatory bowel diseases, based on the literature from July 2017 to Mar. 2023. Subsequently, attention is directed toward elucidating the associations between the bioactivities and structural characteristics (e.g., molecular weight and the presence of specific amino acids within sequences and compositions) of FBPs. We also discuss in silico approaches for FBP screening and their limitations. Finally, we summarize recent advancements in formulation techniques to improve the bioavailability of FBPs in the food industry, thereby contributing to healthcare applications.
Humans ; Peptides/therapeutic use* ; Structure-Activity Relationship ; Functional Food ; Diabetes Mellitus, Type 2/drug therapy* ; Biological Availability ; Alzheimer Disease/drug therapy* ; Inflammatory Bowel Diseases/drug therapy* ; Hypertension/drug therapy* ; Liver Diseases/drug therapy* ; Bioactive Peptides, Dietary

Therapeutic resistance in cancer is responsible for numerous cancer deaths in clinical practice. While target mutations are well recognized as the basis of genetic resistance to targeted therapy, nontarget mutation resistance (or nongenetic resistance) remains poorly characterized. Despite its complex and unintegrated mechanisms in the literature, nongenetic resistance is considered from our perspective to be a collective response of innate or acquired resistant subpopulations in heterogeneous tumors to therapy. These subpopulations, e.g., cancer stem-like cells, cancer cells with epithelial-to-mesenchymal transition, and drug-tolerant persisters, are protected by their resistance traits at cellular and molecular levels. This review summarizes recent advances in the research on resistant populations and their resistance traits. NOTCH signaling, as a central regulator of nongenetic resistance, is discussed with a special focus on its canonical maintenance of resistant cancer cells and noncanonical regulation of their resistance traits. This novel view of canonical and noncanonical NOTCH signaling pathways is translated into our proposal of reshaping therapeutic strategies targeting NOTCH signaling in resistant cancer cells. We hope that this review will lead researchers to study the canonical and noncanonical arms of NOTCH signaling as an integrated resistant mechanism, thus promoting the development of innovative therapeutic strategies.
Neoplasms/metabolism* ; Receptors, Notch/metabolism* ; Disease Resistance/physiology* ; Signal Transduction/physiology* ; Humans ; Drug Resistance, Neoplasm/physiology* ; Molecular Targeted Therapy/methods*

ADC189 is a novel drug of cap-dependent endonuclease inhibitor. In our study, its antiviral efficacy was evaluated in vitro and in vivo, and compared with baloxavir marboxil and oseltamivir. A first-in-human phase I study in healthy volunteers included single ascending dose (SAD) and food effect (FE) parts. In the preclinical study, ADC189 showed potent antiviral activity against various types of influenza viruses, including H1N1, H3N2, influenza B virus, and highly pathogenic avian influenza, comparable to baloxavir marboxil. Additionally, ADC189 exhibited much better antiviral efficacy than oseltamivir in H1N1 infected mice. In the phase I study, ADC189 was rapidly metabolized to ADC189-I07, and its exposure increased proportionally with the dose. The terminal elimination half-life (T_1/2) ranged from 76.69 to 98.28 hours. Of note, food had no effect on the concentration, clearance, and exposure of ADC189. It was well tolerated, with few treatment-emergent adverse events (TEAEs) reported and no serious adverse events (SAEs). ADC189 demonstrated excellent antiviral efficacy both in vitro and in vivo. It was safe, well-tolerated, and had favorable pharmacokinetic characteristics in healthy volunteers, supporting its potential for single oral dosing in clinical practice.
Humans ; Antiviral Agents/therapeutic use* ; Animals ; Male ; Adult ; Mice ; Female ; Endonucleases/antagonists & inhibitors* ; Influenza, Human/drug therapy* ; Young Adult ; Dibenzothiepins/pharmacology* ; Oseltamivir/pharmacology* ; Middle Aged ; Triazines/pharmacology* ; Thiepins/pharmacology* ; Influenza B virus/drug effects* ; Influenza A Virus, H1N1 Subtype/drug effects* ; Pyridines/pharmacology* ; Morpholines ; Pyridones

OBJECTIVE To explore the efficacy and influencing factors of intravitreal injection of ranibizumab in the treatment of macular edema （ME） secondary to retinal vein obstruction （RVO） with different optical coherence tomography （OCT） subtypes. METHODS A retrospective study was conducted on 150 patients with ME secondary to RVO treated at Dept. of Ocular Trauma of Tianjin Eye Hospital between January 1， 2021 and January 1， 2024. According to OCT findings， patients were classified into the diffuse retinal thickening （DRT） group （48 cases）， cystoid macular edema （CME） group （83 cases）， and serous retinal detachment （SRD） group （19 cases）. The best corrected visual acuity （BCVA） and central macular thickness （CMT） were compared before and at 1， 3 and 6 months after treatment. Clinical efficacies of 3 groups were compared based on CMT and fluorescein fundus angiography （FFA） findings before and after treatment. Adverse events and the number of additional injections of ranibizumab during treatment were compared among 3 groups. Using “ineffectiveness” in clinical outcomes at 6 months post- treatment as the dependent variable and patients’ baseline data as the independent variables， a multivariate Logistic regression analysis was conducted to identify risk factors influencing the clinical efficacy of ranibizumab. RESULTS The proportion of branch RVO was significantly higher in the CME and SRD groups than in the DRT group （P＜0.05）， while central RVO （CRVO） was more frequent in the DRT group than in the CME and SRD groups （P＜0.05）. The proportion of patients with ischemia was highest in the SRD group， followed by the CME and DRT groups （P＜0.05）， while the proportion of patients with ischemia in the CME group was significantly higher than that in the DRT group （P＜0.05）. Before treatment， the BCVA and CMT showed no significant differences among the 3 groups （P＞0.05）. After treatment， BCVA and CMT in all 3 groups were significantly reduced compared to those before treatment （P＜0.05）. At different treatment time points， patients in the CME group and SRD group consistently showed significantly higher BCVA and CMT values compared to those in the DRT group （P＜0.05）. Six months after treatment， the differences in clinical efficacy among the 3 groups were statistically significant （P＜0.05）， with the proportion of non-responders in the SRD group being significantly higher than that in the DRT group and the CME group （P＜0.05）. The number of additional injections of ranibizumab in patients from the CME group and the SRD group was significantly more than that in the DRT group （P＜0.05）. The incidence of adverse reactions did not differ significantly among 3 groups （P＞0.05）. Multivariate Logistic regression revealed that CRVO and ischemic type were common risk factors affecting the clinical efficacy of ranibizumab in all 3 groups， while longer disease duration was an independent risk factor for the clinical efficacy of ranibizumab in patients from the DRT group. CONCLUSIONS The therapeutic efficacy of ranibizumab varies among different OCT phenotypes of ME secondary to RVO. DRT patients achieve the best visual improvement， SRD patients have the highest non-response rate， and CME/SRD patients require more additional injections of ranibizumab. CRVO and ischemia are shared adverse prognostic factors for poor prognosis in various subtypes of ME secondary to RVO. Individualized treatment and follow-up strategies should be developed based on OCT patterns and risk factors.