Idiopathic pulmonary fibrosis （IPF） is a chronic interstitial lung disease characterized by dyspnea and progressive deterioration of lung function， which significantly impacts patients' quality of life and imposes a major burden on society. Although modern medicine has increasingly enriched the treatment options for pulmonary fibrosis， unfavorable factors such as high costs and significant side effects contribute to the persistently low survival rate of patients. Studies have shown that the occurrence and development of pulmonary fibrosis are closely related to abnormalities in multiple pathways. Among these， Rho/Rho-associated coiled-coil protein kinase （ROCK） plays a key role in the disease progression of IPF by regulating the cytoskeleton. This pathway not only transmits biochemical molecular signals that promote the progress of fibrosis but also responds to the biomechanical environment， such as the increased lung tissue stiffness caused by the deposition of extracellular matrix （ECM） during the process of pulmonary fibrosis. Therefore， research on this pathway is of great significance for the prevention and treatment of IPF. In recent years， traditional Chinese medicine （TCM） has shown remarkable effects in preventing and treating IPF. Many TCM compounds and active components can reduce the production of α-smooth muscle actin （α-SMA）， CollagenⅠ （ColⅠ）， ColⅢ， and inflammatory factors in lung tissue by regulating the Rho/ROCK signaling pathway. These compounds inhibit the transformation of fibroblasts （FBs） into myofibroblasts （MyoFBs）， intervening in the process of pulmonary fibrosis. Based on this， the article briefly reviews relevant research from recent years， discusses the key role of the Rho/ROCK pathway in pulmonary fibrosis from an interdisciplinary perspective， and summarizes the mechanisms through which TCM regulates Rho/ROCK to prevent and treat IPF， based on resources from PubMed， CNKI， and other databases， in order to provide important references for the broader clinical application of TCM in the prevention and treatment of IPF.

Cancer represents a major worldwide disease burden marked by escalating incidence and mortality. While therapeutic advances persist, developing safer and precisely targeted modalities remains imperative. Nanomedicines emerges as a transformative paradigm leveraging distinctive physicochemical properties to achieve tumor-specific drug delivery, controlled release, and tumor microenvironment modulation. By synergizing passive enhanced permeation and retention effect-driven accumulation and active ligand-mediated targeting, nanoplatforms enhance pharmacokinetics, promote tumor microenvironment enrichment, and improve cellular internalization while mitigating systemic toxicity. Despite revolutionizing cancer therapy through enhanced treatment efficacy and reduced adverse effects, translational challenges persist in manufacturing scalability, longterm biosafety, and cost-efficiency. This review systematically analyzes cutting-edge nanoplatforms, including polymeric, lipidic, biomimetic, albumin-based, peptide engineered, DNA origami, and inorganic nanocarriers, while evaluating their strategic advantages and technical limitations across three therapeutic domains: immunotherapy, chemotherapy, and radiotherapy. By assessing structure-function correlations and clinical translation barriers, this work establishes mechanistic and translational references to advance oncological nanomedicine development.
Humans ; Neoplasms/radiotherapy* ; Immunotherapy/methods* ; Nanoparticles/chemistry* ; Animals ; Nanomedicine/methods* ; Drug Delivery Systems/methods* ; Drug Carriers/chemistry* ; Radiotherapy/methods*

OBJECTIVES: To investigate the association of HOTAIR gene rs920778 single nucleotide polymorphism (SNP) with breast cancer susceptibility and response to HER2-targeted therapy in a Chinese population. METHODS: TaqMan probe-based real-time quantitative PCR was used for genotyping of the rs920778 locus (chr12:54,376,218) in peripheral blood genomic DNA from 287 breast cancer patients and 260 healthy individuals from northern Anhui Province. The genotype (GG, GT and TT) and allele (G/T) distribution frequencies were compared between the two groups to evaluate their association with breast cancer risk. Multivariate logistic regression analysis was conducted to assess the relationship between SNP at this locus and aggressive clinicopathological features (including tumor size, lymph node metastasis, ER/PR/HER2 status, and molecular subtypes) of breast cancer. For the HER2-positive subgroup, the association between rs920778 genotype and responses to dual-targeted therapy (trastuzumab [6 mg/kg q3w]+pertuzumab [420 mg q3w] + docetaxel [75 mg/m²]) was analyzed. The primary endpoints included pathological complete response rate (pCR), objective response rate (ORR), and progression-free survival (PFS). RESULTS: The TT genotype of rs920778 was associated with a significantly increased breast cancer susceptibility (OR=1.54, 95% CI: 1.09-2.19; P=0.017), an advanced tumor stage (P<0.001), lymph node metastasis (P<0.001), and the triple-negative subtype (P<0.001). In HER2-positive patients, TT genotype carriers had a markedly reduced objective response rate to dual HER2-targeted therapy (33.3% vs 89.3%, P=0.001) and a lower pathological complete response rate after neoadjuvant therapy (P=0.018). CONCLUSIONS The TT genotype of HOTAIR rs920778 serves as an independent risk factor for breast cancer susceptibility and aggressive progression in Chinese population and may predict the resistance to HER2-targeted therapies, suggesting its potential as a prognostic biomarker for precision oncology.
Adult ; Aged ; Female ; Humans ; Middle Aged ; Breast Neoplasms/drug therapy* ; Case-Control Studies ; China ; Drug Resistance, Neoplasm/genetics* ; Genetic Predisposition to Disease ; Genotype ; Polymorphism, Single Nucleotide ; Receptor, ErbB-2 ; RNA, Long Noncoding/genetics* ; East Asian People/genetics*

Objective To explore the roles of transcription factor E26 transformation-specific 1(ETS1)and F-box protein 45(FBXO45)in invasion and metastasis in hepatocellular carcinoma cells and the potential molecular mechanism.Methods Jaspar,hTFtarget and Cistrome transcription factor database prediction websites were used to predict the transcription factors of FBXO45.According to the intersection of the predicted results of each database,the expression of FBXO45 was detected after the candidate transcription factors were knockdown in HCCLM3 and Huh7 liver cancer cells,respectively.The most significant influence on FBXO45 expression was selected for further analysis,and chromatin immunoprecipitation assay(ChIP)was used to verify the binding to the FBXO45 promoter.Finally,the potential transcription factor of FBXO45 was identified.The effect of ETS1 overexpression on invasion and migration in HCCLM3 and Huh7 cells was detected by Transwell assay,and the expression levels of epithelial-mesenchymal transition(EMT)pathway proteins were detected by Western blot assay.The effects of FBXO45 knockdown on the invasion and migration under the condition of overexpression of ETS1 were also studied.Results Intersection of FBXO45 transcription factors identified 3 candidate transcription factors,ETS1,SPI1 and YY1.When the 3 transcription factors were knocked down in HCCLM3 and Huh7 cells,respectively,ETS1 knockdown significantly reduced the expression of FBXO45.According to the analysis of The Cancer Genome Atlas(TCGA)data and the Gene Expression Omnibus(GEO)data,the expression levels of ETS1 and FBXO45 were significantly positively correlated(R=0.31,P<0.000 1;R=0.40,P=0.021 9).ChIP suggested that ETS1 could specifically bind to FBXO45 promoter sequence to regulate its expression,confirming that ETS1 was a potential transcription factor of FBXO45.After overexpression of ETS1 in HCCLM3 and Huh7 cells,the invasion and migration abilities of cells were significantly enhanced,and the expression of N-cadherin and Snail was up-regulated(P<0.01).In addition,in the case of ETS1 overexpression,FBXO45 knockdown significantly inhibited the invasion and migration(P<0.01).Conclusion ETS1 activates the transcription of FBXO45 and leads its high expression,which enhances the invasion and migration of HCC cells via EMT pathway and promotes the progression of hepatocellular carcinoma.

Objective To investigate the bacterial community diversity in human Demodex mites, so as to provide insights into unraveling the role of human Demodex mites in them caused infectious diseases. Methods From June to July 2023, Demodex mites were collected from the faces of college students in a university in Wuhu City using the adhesive tape method, and the V4 region of 16S ribosomal RNA (16S rRNA) gene and the internal transcribed spacer (ITS) gene of nuclear ribosomal DNA were amplified on an Illumina PE250 high-throughput sequencing platform. Sequencing data were spliced according to the overlapping relations and filtered to yield effective sequences, and operational taxonomic units (OTUs) was clustered. The diversity index of obtained OUTs was analyzed, and the structure of the bacterial community was analyzed at various taxonomic levels. Results A total of 57 483 valid sequences were obtained using 16S rRNA gene sequencing, and 159 OUTs were classified according to similarity. Then, OUTs at a 97% similarity were included for taxonomic analyses, and the bacteria in Demodex mites belonged to 14 phyla, 20 classes, 51 orders, 72 families, and 94 genera. Proteobacteria was the dominant phylum, and Vibrio, Bradyrhizobium and Variovorax were dominant genera. A total of 56 362 valid sequences were obtained using ITS gene sequencing, and 147 OTUs were obtained, which belonged to 5 phyla, 17 classes, 34 orders, 68 families, and 93 genera and were annotated to Ascomycota, Basidiomycota and Chytridiomycota, with Ascomycota as the dominant phylum, and Alternaria alternata, Epicoccum, Penicillium, and Sarocladium as dominant genera. Conclusions There is a high diversity in the composition of bacterial communities in human Demodex mites, with multiple types of microorganisms and high species abundance.

ObjectiveTo investigate the effects of maltol aluminum exposure on miR-193a-3p, demethylase AlkB homolog 5 (ALKBH5), phosphatase and tensin homolog deleted on chromosome ten (PTEN) and protein kinase B (AKT), and whether miR-193a-3p is involved in aluminum-induced cognitive impairment by regulating ALKBH5/PTEN/AKT signaling pathway. Methods Specific pathogen-free male SD rats were randomly divided into control group and low-, medium- and high- dose groups according to their body weight, with eight rats in each group. Rats in the low-, medium-, and high- dose groups were intraperitoneally injected with maltol aluminum solution at concentrations of 10.00, 20.00, and 40.00 μmol/kg body weight, respectively, while the rats in control group were given an equal volume of 0.9% sodium chloride solution. Rats were injected for five days every week for three months. After injection, the novel object recognized test was used to assess the learning and memory ability of the rats. The relative expression of miR-193a-3p and B-cell lymphocytoma-2 (Bcl-2), Bcl-2 associated X protein (Bax) and cysteine aspartate protease-3 (Caspase-3) mRNA in rat hippocampus was detected using the real-time quantitative polymerase chain reaction. The relative protein expression of ALKBH5, PTEN, and AKT2 in the rat hippocampus was detected using Western blot. Results The discrimination index and the preference index of the new object recognition test of the rats in high-dose group were lower than those in control group and low-dose group (all P<0.05). The relative expression of miR-193a-3p and Bcl-2 mRNA in the hippocampus of the rats in high-dose group was lower than those in control group and low-dose group (all P<0.05). The relative mRNA expression of Bax in the high-dose group was higher than those in the control group and low-dose group (both P<0.05). The relative mRNA expression of Caspase-3 of the rats in the high-dose group was higher than that in the other three groups (both P<0.05). The relative protein expression of ALKBH5 in the hippocampus of the rats in the high-dose group was lower than that in the control group (P<0.05). The relative expression of PTEN protein was higher than those in the control group and low-dose group (both P<0.05). The relative protein expression of AKT2 was lower than those in the control group and low-dose group (both P<0.05). Conclusion Sub-chronic aluminum exposure can inhibit the expression of miR-193a-3p in the hippocampus of rats, which may disrupt the ALKBH5/PTEN/AKT pathway and affect normal neuronal homeostasis and cellular function. This pathway may play an important role in aluminum-induced cognitive impairment.

Objective To investigate the application value of neutrophil count(N),neutrophil percentage(N％),neutrophil to lymphocyte ratio(NLR)and neutrophil to albumin ratio(NAR)in the evaluation of ul-cerative colitis(UC)patients.Methods A total of 87 UC patients admitted to the hospital from May 2022 to July 2023 were collected as the UC group,and 42 healthy people in the same hospital during the same period were selected as the control group.Blood routine and biochemical routine related inflammatory indicators in-cluding lymphocyte count(L),N,lymphocyte percentage(L％),N％,C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),albumin(ALB)were collected,NLR and NAR were calculated.The clinical data of UC patients were collected.According to medical history,modified Mayo scoring system and Montreal classifi-cation criteria,UC patients were divided into clinical types,disease activity and lesion extent.The levels of N,N％,NLR and NAR in the control group and UC group and different subgroups of UC were evaluated.Spearman correlation analysis was used to analyze the correlation between the four indexes and ESR and CRP.The receiver operating characteristic curve was drawn to test the diagnostic efficacy of the four indicators a-lone and in combination in the detection of UC patients,and the best cut-off value,sensitivity and specificity were calculated.Results The levels of N,N％,NLR and NAR in UC group were higher than those in control group,and the differences were statistically significant(P＜0.05).There were significant differences in N,N％,NLR and NAR levels between UC patients with different activity and lesion range(P＜0.05).Spearman correlation analysis showed that CRP level was positively correlated with N,N％,NLR and NAR in UC pa-tients(r=0.392,0.343,0.354,0.503,P＜0.001).ESR level was positively correlated with N,NLR and NAR(r=0.383,0.233,0.475,P＜0.05).The area under the curve of N,N％,NLR and NAR alone and in combi-nation were 0.668,0.702,0.723,0.741 and 0.882,respectively.The sensitivity and specificity of the combina-tion of the four were higher(80.5％and 88.1％,respectively).Conclusion N,N％,NLR and NAR have cer-tain clinical value in the diagnosis,disease activity and lesion extent prediction of UC patients.

The kidney is the body's most important organ and the protein components in urine could be detected for diagnosing certain diseases. The amount of IgG protein in urine could be used to determine the degree of kidney function damage. IgG protein in human urine was detected by vertical flow paper-based microfluidic chip, double-antibody sandwich immunoreaction, and cell phone image processing. The results showed that using an IgG antibody concentration of 500 μg/mL and a gold standard antibody concentration of 100 μg/mL, the image signal showed a good linear relationship in the range of IgG concentration of 0.2-3.2 μg/mL, with R²=0.973 3 achieved. A complete set of detection devices were designed and the detection method showed good non-specificity.
Humans ; Microfluidics ; Immunoglobulin G ; Kidney ; Microfluidic Analytical Techniques

Objective: To explore the relationship between adolescents physical fitness and depressive symptoms, and to provide reference for the early prevention and intervention of depressive symptoms and improvement of physical fitness in Chinese adolescents. Methods: From September to December 2021, a total of 8 102 adolescents were selected by random cluster sampling method in Shanghai, Urumqi, Changsha and Kunming. The Center for Epidemiologic Studies Depression Scale(CES-D) was used to investigate the depressive symptoms, and completed grip strength, standing long jump, 50 m running, modified sitting forward flexion, 20 s repeated traverse, 30 s sit ups, 20 m round trip running (20 m SRT) test. χ 2 test, Goodman Kruskal Gamma and Logistic regression analysis were used to analyze the relationship between physical fitness index(PFI) and depressive symptoms. Results: The overall detection rate of depressive symptoms in adolescents with high level PFI was 23.4%, and the detection rate of low level adolescents was 26.3%, with a statistically significant difference ( χ 2=6.73, P =0.01). There was a significant positive correlation between PFI and depressive symptoms in the high school group ( G=0.09, P <0.05) and the boy group ( G=0.12, P < 0.05 ), and there was no significant association between PFI and depressive symptoms in the junior high school group and the girl group ( P >0.05). After adjusting for gender and age in the Logistic regression model, compared with those with high PFI, the risk of depressive symptoms in those with low PFI was 1.18 times (95% CI =1.05-1.33). Conclusion There is a correlation between physical fitness and depressive symptoms in adolescents. Adolescents with low PFI are at higher risk of developing depressive symptoms than those with high PFI.

Autapses selectively form in specific cell types in many brain regions. Previous studies have also found putative autapses in principal spiny projection neurons (SPNs) in the striatum. However, it remains unclear whether these neurons indeed form physiologically functional autapses. We applied whole-cell recording in striatal slices and identified autaptic cells by the occurrence of prolonged asynchronous release (AR) of neurotransmitters after bursts of high-frequency action potentials (APs). Surprisingly, we found no autaptic AR in SPNs, even in the presence of Sr²⁺. However, robust autaptic AR was recorded in parvalbumin (PV)-expressing neurons. The autaptic responses were mediated by GABA_A receptors and their strength was dependent on AP frequency and number. Further computer simulations suggest that autapses regulate spiking activity in PV cells by providing self-inhibition and thus shape network oscillations. Together, our results indicate that PV neurons, but not SPNs, form functional autapses, which may play important roles in striatal functions.
Parvalbumins/metabolism* ; Corpus Striatum/metabolism* ; Interneurons/physiology* ; Neurons/metabolism* ; Neostriatum