Microplastics are plastic fibers, particles, or films with a particle size of less than 5 mm. They are widely found in water, soil, and atmospheric environments. Because of their small particle size, large surface area, strong adsorptive capacity and other characteristics, they can adsorb heavy metals, persistent organic pollutants, environmental endocrine disruptors and other substances. When humans are exposed to microplastics, the particles can not only have toxic effects on the contact sites, but also penetrate tissue barriers and acess other organs, potentially causing systemic toxic effects. Existing epidemiological and toxicological studies have shown that microplastics can cause damage to the digestive, respiratory, nervous and reproductive systems. However, their bio-distribution, metabolic characteristics and toxic mechanisms have not been fully clarified. This study provides a systematic review of the absorption, distribution, metabolism and excretion characteristics of microplastics in living organisms. By integrating factors such as particle size and chemical composition, this study also investigates the toxic effects of microplastics on multiple organ systems (e.g., digestive and nervous systems) and key organs (e.g., intestine and liver), as well as the underlying molecular mechanisms. The aim is to provide a scientific basis for a comprehensive assessment of the health risks of microplastics and to offer theoretical support for the development of relevant prevention and control strategies.

ObjectiveHyperlipidemia （HLP） is a chronic metabolic disease characterized by abnormal lipid metabolism and is one of the important risk factors for the occurrence of cardiovascular and cerebrovascular diseases. Its incidence has increased year by year， showing a trend toward younger onset. The overall prevalence of HLP among adults in China is as high as 40.40%. Although existing animal models provide important tools for research on the mechanisms of HLP， they generally show insufficient clinical concordance and lack the combined disease-syndrome characteristics of traditional Chinese medicine （TCM） and Western medicine. This article systematically reviews the research progress of HLP animal models， integrates the clinicopathological characteristics of TCM and Western medicine， and proposes new model construction strategies， aiming to provide an experimental basis for accurately analyzing the pathogenesis of HLP and developing integrated TCM-Western medicine therapies. MethodsBased on literature included in PubMed， CNKI， and Wanfang databases over the past 30 years， the construction methods and evaluation systems of HLP animal models were systematically retrieved and summarized. The concordance of existing animal models was calculated according to the new animal model evaluation method proposed by Professor MIAO Mingsan. ResultsAmong existing Western medicine modeling approaches， genetically modified models showed the highest concordance （72%）， followed by dietary induction （66%） and chemical drug induction （60%）. The dietary induction method is the most widely used in practice because of its simple operation and mature technology. Existing TCM modeling approaches are classified into three types， i.e.， spleen deficiency type， phlegm syndrome type， and liver-kidney yin deficiency type. Among them， the phlegm syndrome type shows a high degree of concordance. However， all three types have the problem of non-objective evaluation indicators and insufficient application of tongue and pulse assessment. ConclusionThe construction of existing HLP disease-syndrome combined animal models is still mainly based on Western medicine modeling methods and lacks adequate reflection of TCM syndromes. In the future， HLP animal models that conform to the clinical disease-syndrome characteristics of both TCM and Western medicine may be constructed through multifactor composite modeling strategies， intelligent tongue image analysis via robot learning， objective pulse detection， the establishment of objective evaluation systems for TCM syndromes through big data computing， and the application of cutting-edge technologies.

ObjectiveTo establish and evaluate a rat model of chronic obstructive pulmonary disease (COPD) associated with the traditional Chinese medicine (TCM) phlegm-dampness syndrome. MethodsEighteen SPF-grade 8-week-old male SD rats were randomly assigned to a control group (n=8) and a model group (n=10). The modeling procedure lasted for 19 weeks. Rats in the control group received no intervention. Lipopolysaccharide (LPS; 40 μg per rat per instillation) was instilled intratracheally into rats in the model group at 09:00 on the first day of weeks 1, 5, 9, 13, and 17, for a total of five instillations. Except for the instillation weeks, rats were exposed daily to cigarette smoke in a self-made high-humidity smoke exposure chamber (15 cigarettes/session before week 9 and 20 cigarettes/session from week 9 onward; 30 min/session/day). Body weight was recorded weekly, and general signs and manifestations of TCM phlegm-dampness syndrome were observed. On the day after modeling, rats were anesthetized for pulmonary ventilatory function testing. Tumor necrosis factor-α (TNF-α) and mucin 5AC (MUC5AC) levels in serum and bronchoalveolar lavage fluid (BALF) were measured using enzyme-linked immunosorbent assay (ELISA). Lung tissues were subjected to hematoxylin and eosin (HE) and alcian blue and periodic acid-Schiff staining (AB-PAS) to assess lung tissue morphology and goblet cell hyperplasia. Western blotting was performed to determine TNF-α and MUC5AC protein expression in lung tissue. ResultsGeneral signs and overall condition: Compared with the control group, body weight in the model group was significantly decreased from week 3 onward (P<0.01). Rats showed yellowish fur, sluggish activity, reduced movement, rapid/labored breathing, and increased oral/nasal secretions. Pulmonary ventilatory function: Compared with the control group, minute ventilation and tidal volume (both P<0.01) and dynamic compliance (P<0.05) were decreased, whereas elastic resistance was markedly increased (P<0.01) in the model group. Inflammatory factors and mucus-related proteins: Compared with the control group, TNF-α and MUC5AC levels in serum and BALF, as well as their protein levels in lung tissue, were significantly elevated in the model group (all P<0.01). Histopathology: HE staining showed obvious alveolar dilatation and rupture with partial coalescence into bullae, and inflammatory cell infiltration in bronchiolar lumens. AB-PAS staining revealed increased goblet cells in bronchiolar mucosal epithelium and mucus plug formation in the lumen. ConclusionThis protocol can reproduce a COPD rat model with manifestations consistent with TCM phlegm-dampness syndrome, reduced pulmonary ventilation function, and pathological features of emphysema, inflammation, and chronic bronchitis, thereby providing reliable support for subsequent studies on TCM treatment of COPD with phlegm-dampness syndrome.

Objective To analyze the characteristics of postoperative hospital-acquired infections and drug sensitivity in lung transplant recipients over the past 5 years in a single center. Methods A total of 724 lung transplant recipients at Wuxi People's Hospital from January 2019 to December 2023 were selected. Based on the principles of hospital-acquired infection diagnosis, a retrospective analysis was conducted on the hospital infection situation and infection sites of lung transplant recipients, and an analysis of the distribution of hospital-acquired infection pathogens and their antimicrobial susceptibility test status was performed. Results Among the 724 lung transplant recipients, 275 cases of hospital-acquired infection occurred, with an infection rate of 38.0%. The case-time infection rate decreased from 54.2% in 2019 to 22.8% in 2023, showing a downward trend year by year (Z=30.98, P<0.001). The main infection site was the lower respiratory tract, accounting for 73.6%. The pathogens were mainly Gram-negative bacteria, with the top four being Acinetobacter baumannii (37.1%), Pseudomonas aeruginosa (17.3%), Klebsiella pneumoniae (13.7%), and Stenotrophomonas maltophilia (13.4%), with imipenem resistance rates of 89%, 53%, 58% and 100%, respectively. Gram-positive bacteria were mainly Staphylococcus aureus (3.6%), with a methicillin resistance rate of 67%. Conclusions Over the past 5 years, the hospital-acquired infections in lung transplant recipients have shown a downward trend, mainly involving lower respiratory tract infections, with the main pathogens being Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae, all of which have high resistance rates to imipenem.

Objective To explore the relationships of microRNA-125b(miR-125b),microR-NA-142-5p(miR-142-5p)and microRNA-140-3p(miR-140-3p)with sensitivity to programmed death receptor-1(PD-1)antibody therapy in patients with non-small cell lung cancer(NSCLC)and their clinical significance.Methods A total of 219 NSCLC patients were selected and divided into sensitive group(n=92)and non-sensitive group(n=127)based on their sensitivity to PD-1 anti-body therapy.Serum levels of miR-125b,miR-142-5p and miR-140-3p were compared between the two groups.A new combined predictor was constructed using miR-125b,miR-142-5p,and miR-140-3p through a Logistic regression model.The predictive performance was evaluated using the receiver operating characteristic(ROC)curve,and data were substituted into the equation forpredictive vali-dation.Results The serum level of miR-125b was higher in the non-sensitive group than that in the sensitive group,while the serum levels of miR-142-5pand miR-140-3p were lower in the non-sensitive group(P＜0.05).Logistic regression analysis showed that an increased level of miR-125b was an independent risk factor for sensitivity to PD-1 antibody therapy in NSCLC patients(P＜0.05),while increased levels of miR-142-5p and miR-140-3p were independent protective factors(P＜0.05).The optimal cut-off value for the combined predictor was 0.117,with a sensitivity of 90.22％,a specificity of 85.04％,and an accuracy of 87.21％.ROC curve analysis revealed that the area under the curve(AUC)for the combined predictor in predicting sensitivity to PD-1 antibod-y therapy was 0.928,which was significantly larger than the AUCs of 0.825,0.817 and 0.772 for miR-125b,miR-142-5p and miR-140-3p,respectively(P＜0.05).A new equation was obtained by transforming the original Logistic regression equation,and data from three randomly selected pa-tients were substituted into the equation for calculation,with predictive results being consistent with clinical reality.Conclusion The miR-125b,miR-142-5p and miR-140-3p are all associated with sensitivity to PD-1 antibody therapy in NSCLC patients and can serve as biomarkers for predicting sensitivity to PD-1 antibody therapy.The combined predictor based on these three microRNAs can further enhance predictive value and provide more reliable reference information for clinical treat-ment decisions.

Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans ; Cholangiocarcinoma/drug therapy* ; Immunotherapy/methods* ; Bile Duct Neoplasms/drug therapy* ; Molecular Targeted Therapy/methods*

Geminiviruses cause substantial crop yield losses worldwide. The replication initiator protein (Rep) encoded by geminiviruses is indispensable for geminiviral replication. The Rep protein encoded by beet severe curly top virus (BSCTV, genus Curtovirus, family Geminiviridae) induces VARIANT IN METHYLATION 5 (VIM5) expression in Arabidopsis leaves upon BSCTV infection. VIM5 functions as a ubiquitination-related E3 ligase to promote the proteasomal degradation of methyltransferases, resulting in reduction of methylation levels in the BSCTV C2-3 promoter. However, the specific domains of Rep responsible for VIM5 induction remain poorly characterized. Although Rep proteins from several geminiviruses act as viral suppressors of RNA silencing (VSRs), whether BSCTV Rep also possesses VSR activity remains to be illustrated. In this study, we employed a transient expression system in the 16c-GFP transgenic and the wild-type Nicotiana benthamiana plants to analyze the VSR and the VIM5-inducing activities of different truncated Rep proteins haboring distinct domains. We found that the N-terminal domain (amino acids 1-180) of Rep suppressed GFP silencing in 16c-GFP transgenic N. benthamiana leaves. The minimal N-terminal fragment (amino acids 1-104) induced VIM5 expression upon co-infiltration, while C-terminal truncations lacked VIM5-inducing activity. Our results indicate that the N-terminal domain of Rep encoded by BSCTV mediates the suppression of RNA silencing and induces VIM5 expression. Thus, our findings contribute to a better understanding of interactions between geminiviral Rep and plant hosts.
Geminiviridae/genetics* ; Nicotiana/metabolism* ; Arabidopsis/metabolism* ; RNA Interference ; Viral Proteins/metabolism* ; Arabidopsis Proteins/metabolism* ; Plants, Genetically Modified/metabolism* ; Protein Domains ; Plant Diseases/virology* ; Methyltransferases/metabolism* ; Ubiquitin-Protein Ligases/metabolism* ; DNA Helicases/genetics*

Objective To explore the risk factors for healthcare-associated infection(HAI)in lung transplant re-cipients(LTRs),and construct a predictive nomogram model.Methods Clinical data of patients who underwent lung transplant in Wuxi People's Hospital from January 2019 to December 2023 were analyzed retrospectively.The patients were divided into a training set(n=506)and a validation set(n=218).Independent risk factors were screened through LASSO regression,and multivariate logistic regression was included to construct a nomogram pre-diction model.The discrimination,calibration,and clinical applicability of the model were evaluated using receiver operating characteristic(ROC)curves,Hosmer-Lemeshow goodness-of-fit,and decision curves.Results Among the 506 LTRs,201 developed HAIs,with an incidence of 39.72％.The major infection site was lower respiratory tract,and the major pathogen were Gram-negative bacilli(Acinetobacter baumannii).Older age,use of extracorpo-real membrane oxygenation(ECMO),double-lung transplant,surgery duration＞3 hours,long duration of contin-uous fever,frequent abnormal blood routine examination,and long duration of combined use of antimicrobial agents were identified as independent risk factors for HAI after lung transplant.The ROC curve analysis results showed that the areas under the curve(AUCs)of the training set and the validation set were 0.74(95％CI:0.70-0.78)and 0.71(95％CI:0.64-0.78),respectively.The Hosmer-Lemeshow test results showed that there was no sta-tistically significant difference between the predictive and actual probability of HAI(P＞0.05).The clinical decision curve results indicated that the model had clinical benefits at a threshold probability value of 7％-71％.Conclusion The nomogram prediction model constructed in this study can effectively evaluate the risk of postoperative infection in LTRs.The model is stable and has high clinical application value,providing scientific reference for postoperative infection prevention and control.

Objectives:To investigate the physical growth status of pediatric patients with transfusion-dependent thalassemia (TDT) and analyze the effects of treatment-related and socioeconomic factors on physical growth.Methods:Based on the specialized thalassemia database from gene therapy clinical research at the Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, we collected data on height and weight development, family economic status, and medical records of 338 pediatric patients with TDT from October 2023 to May 2024. The length/height-for-age and body mass index (BMI) -for-age were classified based on the Growth Standard for Children under 7 Years of Age, Standard for Height Level Classification among Children and Adolescents Aged 7-18 Years, and Dietary Guidelines for Chinese Residents. Logistic regression analysis was conducted to assess the effects of family economic status and disease-related treatment on length/height-for-age and BMI-for-age.Results:Among the 338 patients, 118 were children and 220 were adolescents (192 males and 146 females), with a median age of 12 years (range: 0.8-18) and a median diagnosis duration of 10.3 years (range: 0.5-17.9). Subtypes included α-thalassemia [21 cases (6.2%) ], β-thalassemia [288 cases (85.2%) ], and combined αβ-thalassemia[29 cases (8.6%) ]. The monthly household income of patients was concentrated in 3 000-5 000 yuan (39.9%) and 5 001-10 000 yuan (34.9%), whereas 67.2% of the families had monthly medical expenses of <3 000 yuan. Of the patients, 75.5% received their first transfusion before 1 year of age. The proportions of children and adolescents with pretransfusion hemoglobin (HGB) of ≤70 g/L were 4.2% and 6.4%, respectively. Adolescents demonstrated significantly higher rates of transfusion frequency of <4 weeks/session, monthly red blood cell infusion of >2 U, serum ferritin (SF) of ≥5 000 μg/L, iron chelation therapy, and splenectomy compared with children (all P<0.05). Of the 338 patients, 26.0%, 22.8%, and 8.9% demonstrated stunted growth, underweight, and concurrent stunted growth with underweight, respectively. No significant difference was observed in the stunted growth rates between children (22.9%) and adolescents (27.7%) ( P=0.402). However, the underweight rate in adolescents (26.8%) was significantly higher than that in children (15.3%) ( P=0.023). The multivariate analysis determined the following risk factors for stunted growth: monthly household income of <10 000 yuan (5 001-10 000 yuan: OR=5.49, 95% CI: 1.48-35.76; 3 000-5 000 yuan: OR=6.87, 95% CI: 1.88-44.60; <3 000 yuan: OR=9.29, 95% CI: 2.20-64.77), pretransfusion HGB of ≤70 g/L ( OR=3.25, 95% CI: 1.07-10.18), and SF of ≥5 000 μg/L ( OR = 3.04, 95% CI: 1.20-7.70). Longer diagnostic duration was associated with underweight ( OR=1.10, 95% CI: 1.01-1.20) . Conclusions:Children and adolescents with TDT with pretransfusion SF of ≥5 000 μg/L, HGB of ≤70 g/L, low monthly household income, or longer diagnosis duration were significantly more likely to experience delayed physical growth.

Objective:To explore the correlation between abnormal vital signs (e.g., heart rate, oxygen saturation, and body temperature) and acute exacerbations in patients with chronic obstructive pulmonary disease (COPD), as well as to evaluate the clinical value of continuous monitoring via wearable devices for the early warning and intervention.Methods:A multicenter cross-sectional study enrolled 335 patients with stable chronic obstructive pulmonary disease (COPD) from 12 community health centers in Beijing and Chengdu between June 2023 and May 2024. General demographic and clinical data were collected, and each participant underwent continuous monitoring of resting heart rate, oxygen saturation, and body temperature using wearable devices for 21 days. Based on whether participants had experienced acute exacerbations requiring outpatient, emergency, or inpatient treatment within the previous year, they were categorized into the acute exacerbation group and the non-exacerbation group. Differences in physiological parameters between the acute exacerbation group and non-exacerbation group were analyzed, and contributing factors were assessed using logistic regression analysis.Results:A total of 335 patients with stable COPD were enrolled, including 252 cases (75.22%) in the acute exacerbation group and 83 cases (24.78%) in the non-acute exacerbation group. There were no statistically significant differences in age, sex distribution, comorbidities, or baseline lung function between the two groups (all P>0.05). Compared with the non-acute exacerbation group, patients in the acute exacerbation group had a faster resting heart rate((76.01 ± 7.78) beats/min vs. (72.72 ± 7.35) beats/min, t=3.126, P=0.002), a higher proportion of patients with decreased oxygen saturation (1.75% (0.97%, 3.03%) vs. 0.86% (0.44%, 1.65%), Z=11.086, P=0.001), and a higher proportion of patients with elevated body temperature (0.60% (0.39%, 1.03%) vs. 0.31% (0.17%, 0.54%), Z=7.314, P=0.007). Logistic regression analysis showed that advanced age ( OR=1.051, 95% CI: 1.023-1.080), increased heart rate ( OR=1.055, 95% CI:1.013-1.098), decreased oxygen saturation ( OR=1.197, 95% CI:1.023-1.400), and elevated body temperature ( OR=1.777, 95% CI:1.148-2.752) were positively associated factors for acute exacerbation of COPD. Conclusions:Abnormalities in physiological indicators such as heart rate, oxygen saturation, and body temperature are associated with acute exacerbations in COPD patients. Continuous monitoring using wearable devices may provide a new method for early warning and timely intervention in COPD exacerbations.