Objective To explore the feasibility and reference value of allogeneic lung transplantation and postoperative monitoring in miniature pigs for lung transplantation research. Methods Two miniature pigs (R1 and R2) underwent left lung allogeneic transplantation. Complement-dependent cytotoxicity tests and blood cross-matching were performed before surgery. The main operative times and partial pressure of arterial oxygen (PaO₂) after opening the pulmonary artery were recorded during surgery. Postoperatively, routine blood tests, biochemical blood indicators and inflammatory factors were detected, and pathological examinations of multiple organs were conducted. Results The complement-dependent cytotoxicity test showed that the survival rate of lymphocytes between donors and recipients was 42.5%-47.3%, and no agglutination reaction occurred in the cross-matching. The first warm ischemia times of D1 and D2 were 17 min and 10 min, respectively, and the cold ischemia times were 246 min and 216 min, respectively. Ultimately, R1 and R2 survived for 1.5 h and 104 h, respectively. Postoperatively, in R1, albumin (ALB) and globulin (GLB) decreased, and alanine aminotransferase increased; in R2, ALB, GLB and aspartate aminotransferase all increased. Urea nitrogen and serum creatinine increased in both recipients. Pathological results showed that in R1, the transplanted lung had partial consolidation with inflammatory cell infiltration, and multiple organs were congested and damaged. In R2, the transplanted lung had severe necrosis with fibrosis, and multiple organs had mild to moderate damage. The expression levels of interleukin-1β and interleukin-6 increased in the transplanted lungs. Conclusions The allogeneic lung transplantation model in miniature pigs may systematically evaluate immunological compatibility, intraoperative function and postoperative organ damage. The data obtained may provide technical references for subsequent lung transplantation research.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Objective: To investigate the characteristics of malignant tumor incidence and mortality in cancer registration areas of Sichuan Province in 2021. Methods: Cancer registration data from 142 registries in Sichuan Province in 2021 were collected via the China Cancer Registry Platform. Crude incidence and crude mortality were calculated. The Chinese population-standardized incidence and world population-standardized incidence were standardized using the age structure of the standard population from the Fifth National Population Census in 2000 and Segi's world standard population. Descriptive analyses examined the distribution of rates by genders, urban/rural areas, and ages, and the ranking of leading cancer sites. Results: In 2021, there were 248 600 new malignant tumor cases reported in Sichuan Province, with a crude incidence of 296.37/100 000. The Chinese population-standardized incidence and world population-standardized incidence were 164.67/100 000 and 160.47/100 000, respectively. There were 158 673 malignant tumor deaths, with a crude mortality of 189.16/100 000. The Chinese population-standardized mortality and world population-standardized mortality were 92.47/100 000 and 92.00/100 000, respectively. The Chinese population-standardized incidence and mortality in males were higher than in females (179.56/100 000 vs. 151.62/100 000, 125.09/100 000 vs. 60.35/100 000). The Chinese population-standardized incidence and mortality in urban areas were higher than in rural areas (175.74/100 000 vs. 157.54/100 000, 93.63/100 000 vs. 91.82/100 000). Both the crude incidence and crude mortality increased with age. The top ten malignant tumors by crude incidence were lung cancer, colorectal cancer, liver cancer, breast cancer, esophageal cancer, gastric cancer, cervical cancer, prostate cancer, thyroid cancer, and corpus uteri cancer, accounting for 76.33% of all new cases. The top ten by crude mortality were lung cancer, liver cancer, esophageal cancer, colorectal cancer, gastric cancer, breast cancer, pancreatic cancer, cervical cancer, prostate cancer, and brain tumors, accounting for 82.39% of all cancer deaths. Conclusions In registration areas of Sichuan Province, the incidence and mortality of malignant tumors are relatively low. Key populations such as males, urban residents, and the elderly require focused prevention and control efforts. Comprehensive measures should be prioritized for malignant tumors including lung cancer, liver cancer, esophageal cancer, gastric cancer, colorectal cancer, and breast cancer.

Ferroptosis is a form of programmed cell death characterized by overwhelmed lipid oxidation, and it has emerged as a promising strategy for cancer therapy. Enhanced ferroptosis could overcome the limitations of conventional therapeutic modalities, particularly in difficult-to-treat tumors. In this study, we developed a dual-modality therapy in nanomedicine by combining paclitaxel (PTX) chemotherapy and pyropheophorbide-a (Ppa) phototherapy. Heparin (HP) was grafted with poly(N-(2'-hydroxy) propyl methacrylamide) (pHPMA) using reversible addition-fragmentation chain transfer polymerization to form HP-pHPMA (HH), which was utilized to deliver Ppa and PTX, yielding HP-pHPMA-Ppa (HH-Ppa) and HP-pHPMA-PTX (HH-PTX), respectively. The prodrug-based combinational nanomedicine (HH-PP) was formed by co-assembly of HH-PTX and HH-Ppa. It was found that HH-PP treatment significantly disrupted lipid metabolism in triple-negative breast cancer (TNBC) cells, induced extensive lipid oxidation, and promoted ferroptosis. In vivo, HH-PP intervention achieved a tumor growth inhibition rate of 86.63% and activated adaptive immunity with an elevated CD8⁺ cytotoxic T cell infiltration level. This combinational nanomedicine offers a promising platform for co-delivery of multiple therapeutic agents. It exerts a promising anti-tumor effect via enhanced ferroptosis and ferroptosis-induced immune activation by disrupting lipid metabolism in TNBC cancer cells.

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OBJECTIVE: Baicalein has been reported to have wide therapeutic effects that act through its anti-inflammatory activity. This study examines the effect and mechanism of baicalein on sepsis-induced cardiomyopathy (SIC). METHODS: A thorough screening of a small library of natural products, comprising 100 diverse compounds, was conducted to identify the most effective drug against lipopolysaccharide (LPS)-treated H9C2 cardiomyocytes. The core target proteins and their associated signaling pathways involved in baicalein's efficacy against LPS-induced myocardial injury were predicted by network pharmacology. RESULTS: Baicalein was identified as the most potent protective agent in LPS-exposed H9C2 cardiomyocytes. It exhibited a dose-dependent inhibitory effect on cell injury and inflammation. In the LPS-induced septic mouse model, baicalein demonstrated a significant capacity to mitigate LPS-triggered myocardial deficits, inflammatory responses, and ferroptosis. Network pharmacological analysis and experimental confirmation suggested that hypoxia-inducible factor 1 subunit α (HIF1-α) is likely to be the crucial factor in mediating the impact of baicalein against LPS-induced myocardial ferroptosis and injury. By combining microRNA (miRNA) screening in LPS-treated myocardium with miRNA prediction targeting HIF1-α, we found that miR-299b-5p may serve as a regulator of HIF1-α. The reduction in miR-299b-5p levels in LPS-treated myocardium, compared to the control group, was reversed by baicalein treatment. The reverse transcription quantitative polymerase chain reaction, Western blotting, and dual-luciferase reporter gene analyses together identified HIF1-α as the target of miR-299b-5p in cardiomyocytes. CONCLUSION Baicalein mitigates SIC at the miRNA level, suggesting the therapeutic potential of it in treating SIC through the regulation of miR-299b-5p/HIF1-α/ferroptosis pathway. Please cite this article as: Zhou WY, Du JK, Liu HH, Deng L, Ma K, Xiao J, Zhang S, Wang CN. Baicalein attenuates lipopolysaccharide-induced myocardial injury by inhibiting ferroptosis via miR-299b-5p/HIF1-α pathway. J Integr Med. 2025; 23(5):560-575.
Flavanones/pharmacology* ; Animals ; MicroRNAs/genetics* ; Lipopolysaccharides ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Ferroptosis/drug effects* ; Mice ; Myocytes, Cardiac/metabolism* ; Signal Transduction/drug effects* ; Rats ; Male ; Mice, Inbred C57BL ; Cardiomyopathies/etiology* ; Cell Line ; Sepsis/complications*

Objective: To analyze the effects of blue light on the formation of kidney stones. Methods: A total of 40 rats were randomly divided into 4 groups：A，B，C，and D，with 10 rats in each group.Rats in groups C and D were administered with a mixture of 10 g/L ethylene glycol，20 g/L ammonium chloride，and 100 g/L calcium gluconate via gavage (2 mL per mouse)，while rats in groups A and B received an equal volume of physiological saline via gavage.From the second day after gavage，rats in groups A and C were subjected to twice-daily blue light irradiation (one hour per session) as an intervention，while rats in groups B and D were subjected to fluorescent lamp irradiation using the same method.After 4 weeks of intervention，the 24-hour urine samples were collected，and the rats were then euthanized for the collection of blood and kidney tissue samples.Serum levels of antidiuretic hormone (ADH)，urinary Ca ，and urinary oxalate (Oxa) were measured.Levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in kidney tissues were detected using ELISA.Von Kossa staining was performed to observe pathological changes in kidney tissues and the presence of calcium salt crystals in the kidneys. Results: Compared with groups A and B，groups C and D showed higher accumulation of calcium salt crystals in renal tissues，as well as elevated levels of ADH，urinary Ca ，urinary Oxa，and MDA in renal tissues, additionally，the SOD level in renal tissues was lower (P<0.05).Compared with group D，group C exhibited higher accumulation of calcium salt crystals in renal tissues，along with increased levels of ADH，urinary Ca ，urinary Oxa，and MDA in renal tissues；conversely，the SOD level in renal tissues was lower (P<0.05). Conclusion: Blue light may increase the formation of kidney stones in rats by promoting the secretion of ADH in serum and oxidative stress in kidney tissues through the brain-kidney axis.

Objective To investigate the effects of Caenorhabditis elegans(C.elegans)endogenous U6 promoters on dpy-10 gene editing efficiency.Methods We screened endogenous U6 small nuclear RNA(snRNA)genes of C.elegans from the WormBase database and constructed 14 editing plasmids targeting dpy-10 by replacing the U6r07e5.16 promoter in the pSX524 plasmid(Peft-3::cas9::tbb-2 terminator::U6 r07e5.16::dpy-10 sgRNA)through molecular cloning.Gene editing was performed in wild-type C.elegans using a standardized microinjection protocol.Gene editing efficiency and the high-efficiency gene editing index were quantified based on the screening of dpy-10 mutant phenotypes in the F1 progeny.Results A total of 15 U6 snRNA genes(r07e5.16,f35c11.9,t20d3.13,k09b11.15,k09b11.16,w05b2.8,c28a5.7,f54c8.9,k09b11.11,k09b11.12,k09b11.14,t20d3.12,f54c8.8,f54c8.10,and k09b11.13)were identified from the WormBase database.Based on the editing efficiency and high-efficiency gene editing index,the activity of these promoters was evaluated,and 4 U6 promoters(w05b2.8,c28a5.7,f54c8.9,and k09b11.11)were found to have significantly enhanced gene editing success rates,outperforming other promoters,including U6r07e5.16 and U6k09b11.12,which are commonly used in the C.elegans research community.Notably,the gRNAF+E scaffold did not show superior editing efficiency over the gRNA scaffold when paired with the optimal U6w05b2.8 promoter.Conclusion In this study,U6 promoters that significantly improve gene editing efficiency in C.elegans are identified and the critical role of promoter optimization in CRISPR-Cas9 systems is highlighted.These findings provide a valuable foundation for improving genome editing strategies and offer new ideas for optimizing the CRISPR technology applied in nematode research.

Objective To optimize the real-time quantitative polymerase chain reaction(RT-qPCR)data analysis process through mathematical principles by replacing the biased 2-??CT method with a more rigorous 2-CT method,thereby improving the accuracy of gene expression quantification analysis.Methods Essentially,the CT value serves as the exponent in a base-2 exponential equation within the logic of comparative CT method.In the traditional 2-??CT method,the arithmetic means of raw CT and ΔCT values are directly calculated and the exponential nature of CT data is overlooked,which may introduce systematic bias to the calculation results.We propose a new method,entitled the 2-CT method,in which all calculations are based on the transformation of CT values into 2-CT.This includes computing the relative initial expression levels of target and reference genes within each sample,the relative abundance of the target gene,and its fold change across groups.Statistical comparisons are then performed based on fold change values.By strictly adhering to the exponential nature of of CT values,the biases introduced by arithmetic averaging at the CT or ΔCT level are avoided.We applied this method to multiple RT-qPCR datasets to evaluate the differences between the traditional 2-??CT and the proposed 2-CT methods in gene expression quantification,as well as the effect of the differences.Results In the original dataset from LIVAK and SCHMITTGEN,the two methods produced similar results.However,in the cadmium exposure experiment,findings from the 2-??CT method indicated that 8-hour cadmium exposure caused an increase of irg-6 gene expression in Caenorhabditis elegans from 1.314-fold to 7.125-fold(P=0.000 2).In contrast,findings from the 2-CT method showed a fold change from 1.0 to 4.124(P=0.001 5),a 70%difference between the two methods.Conclusion The2-CT method provides a mathematically more rigorous approach that more accurately reflects gene expression changes,particularly in experiments with high CT variability.It offers a more reliable computational paradigm for quantitative gene expression analysis.