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.

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 report a case of hepatitis B virus （HBV） reactivation induced by iparomlimab and tuvonralimab， summarize the clinical characteristics and potential mechanisms of such adverse reactions induced by immune-checkpoint inhibitors （ICIs）， and provide references for clinical application. METHODS From the perspective of a clinical pharmacist， a retrospective analysis was conducted on the treatment course of a patient with metastatic cervical cancer who experienced HBV reactivation after receiving iparomlimab and tuvonralimab. Additionally， an analysis of the correlation with adverse reactions was performed， and the clinical characteristics， risk factors， potential mechanisms， key points of treatment approaches and pharmaceutical care associated with HBV reactivation induced by ICIs were summarized. RESULTS & CONCLUSIONS The patient developed HBV reactivation and severe liver injury after using iparomlimab and tuvonralimab. The condition improved following drug discontinuation， and symptomatic treatment such as glucocorticoids. According to Naranjo’s Assessment Scale and China’s Measures for the Reporting and Monitoring of Adverse Drug Reactions， the association between iparomlimab and tuvonralimab and HBV reactivation was judged as “highly probable”， and it was identified as a new adverse reaction； the correlation between iparomlimab and tuvonralimab， paclitaxel and liver injury was “highly probable”. HBV reactivation in hepatitis B patients receiving standardized antiviral therapy is very rare after ICIs treatment； HBV reactivation is related to the overactivation of the immune system and disruption of immune balance induced by ICIs. For such patients， glucocorticoids should be administered for treatment， accompanied by pharmaceutical care， including pre- medication risk assessment and monitoring of relevant indicators during treatment.

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.

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.

BACKGROUND:The imbalance between proliferation and apoptosis of chondrocytes plays an important role in the occurrence and development of osteoarthritis. Previous studies have found that hsa-miR-3202 is involved in regulating the proliferation and apoptosis of various cells. However,no studies have explored the correlation between hsa-miR-3202 and osteoarthritis.OBJECTIVE:To investigate the expression of hsa-miR-3202 in osteoarthritic chondrocytes and its effect on the proliferation and apoptosis of chondrocytes. METHODS:(1) MicroRNAs differentially expressed in osteoarthritic chondrocytes were screened by biogenic analysis. Based on the current research situation at home and abroad,hsa-miR-3202 was selected for follow-up studies,and its target genes were predicted by gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. (2) Human normal chondrocyte cell lines C28/I2 in logarithmic growth phase were selected and randomly divided into four groups for culture:in normal group,cells were cultured in normal medium for 24 hours,the medium was then changed to normal medium for another 6 hours of culture,and changed to normal medium for subsequent culture;in lipopolysaccharide group,cells were cultured in lipopolysaccharide-containing medium for 24 hours,the medium was then changed to normal medium for another 6 hours,and changed to normal medium for subsequent culture;in lipopolysaccharide+NC group,cells were cultured in lipopolysaccharide-containing medium for 24 hours,and then transfected with has-miR-3202 mimics control for 6 hours,and the medium was change to normal medium for subsequent culture;in lipopolysaccharide+hsa-miR-3202 mimics group,cells were cultured in lipopolysaccharide-containing medium for 24 hours and then transfected with has-miR-3202 mimics for 6 hours,and the medium was changed to normal medium for subsequent culture. After further 48 hours of culture,the expression level of hsa-miR-3202 was detected by fluorescence quantitative PCR and cell apoptosis was detected by flow cytometry. After further culture of 0-72 hours,cell proliferation activity was detected by cell counting kit-8. RESULTS AND CONCLUSION:Bioinformatics analysis results indicated that hsa-miR-3202 was significantly down-regulated in osteoarthritic chondrocytes. GO functional enrichment and KEGG pathway enrichment showed that the function of hsa-miR-3202 target gene was closely related to cell growth and apoptosis. The results of in vitro cell experiments showed that compared with the normal group,the expression level of hsa-miR-3202 and proliferation ability of chondrocytes were significantly decreased in the lipopolysaccharide group (P<0.05),while the apoptotic rate was significantly increased (P<0.05). Compared with the lipopolysaccharide group,the expression level of hsa-miR-3202 and proliferation ability of chondrocytes were significantly increased in the lipopolysaccharide+hsa-miR-3202 mimics group (P<0.05),while the apoptotic rate was significantly decreased (P<0.05). To conclude,the expression of hsa-miR-3202 is down-regulated in osteoarthritic chondrocytes to inhibit cell proliferation and promote cell apoptosis,thus affecting the occurrence and development of osteoarthritis.

Prostate cancer is a malignant tumor that primarily arises from the epithelial tissue of the prostate in men. With the aggravation of population aging in China， the incidence rate of this disease has been continuously rising. Although the exact cause of prostate cancer remains unclear， it has been proven to be closely related to various factors， including individual genetic susceptibility， genetic mutations， dietary habits， and lifestyle. Research has shown that abnormal activation of the Wnt/β-catenin signaling pathway also plays an important role in the occurrence and development of prostate cancer. Multiple experimental results have revealed that traditional Chinese medicine （TCM）， with its multi-target and multi-stage mechanisms of action， exerts significant regulatory effects on key biological processes such as proliferation， migration， invasion， angiogenesis， and epithelial-mesenchymal transition （EMT） of prostate cancer cells. TCM has shown excellent potential in preventing prostate cancer progression and improving patient prognosis and has become a research focus in prostate cancer treatment in recent years. Based on this， this study reviewed the research on the regulation of the Wnt/β-catenin signaling pathway by TCM in the treatment of prostate cancer at home and abroad. It analyzed the mechanisms by which TCM intervention exerts anti-prostate cancer effects via this signaling pathway， identifying 29 different types of active ingredients in TCM， including alkaloids （e.g.， capsaicin， berberine）， flavonoids （e.g.， icariin and hyperoside）， polyphenols （e.g.， gastrodin and honokiol）， terpenes （e.g.， oridonin）， quinones （e.g.， aloe-emodin）， coumarins （e.g.， agrimonolide）， and saponins （e.g.， saikosaponin-d）. Additionally， one TCM medicinal substance （arsenic）， one drug pair （Danggui - Qieyi combination）， and two TCM formulae （Yishen Tonglong Tang and Guben Qingyuan Formula） were included. The study aims to deepen the understanding of the pathological mechanism of prostate cancer and to explore possible therapeutic targets， thereby providing new perspectives and approaches for clinical research and new drug development， and ultimately promoting the advancement and innovation of prostate cancer treatment strategies.