[This corrects the article DOI: 10.1016/j.apsb.2021.10.012.].

OBJECTIVE: In order to enhance the efficacy of anti-breast cancer, paclitaxel nanoparticles (PTX NPs) and polypyrrole nanoparticles (PPy NPs) were combined with photothermal therapy and chemotherapy. At the same time, the two dosage forms of PTX NPs and PTX NPs gel were compared. METHODS: PTX NPs were prepared by self-assembly method, and then the cytotoxicity in vitro was investigated by Methyl thiazolyl tetrazolium (MTT) and other methods, and the efficacy and side effects in vivo were further investigated. RESULTS: The average hydrated diameter, PDI and electric potential of PTX NPs were (210.20 ± 1.57) nm, (0.081 ± 0.003) mV and (15.80 ± 0.35) mV, respectively. MTT results showed that the IC₅₀ value of PTX NPs on 4 T1 cells was 0.490 μg/mL, while that of PTX injection was 1.737 μg/mL. The cell inhibitory effect of PTX NPs was about 3.5 times higher than that of PTX injection. The tumor inhibition rates of PTX NPs and gel were 48.64% and 56.79%, respectively. Together with local photothermal stimulation, the tumor inhibition rate of the PTX NPs reached 91.05%, surpassing that of the gel under the same conditions (48.98%), moreover, the organ index and H&E staining results of PTX NPs showed a decrease in toxicity. CONCLUSION This combination therapy can significantly enhance the effect of anti-breast cancer, and the synergistic effect of chemotherapy and light and heat provides a feasible and effective strategy for the treatment of tumor.

Diabetic cardiomyopathy (DCM) is a medical condition characterized by cardiac remodeling and dysfunction in individuals with diabetes mellitus. Sarcoplasmic reticulum (SR) and mitochondrial Ca²⁺ overload in cardiomyocytes have been recognized as biological hallmarks in DCM; however, the specific factors underlying these abnormalities remain largely unknown. In this study, we aimed to investigate the role of a cardiac-specific long noncoding RNA, D830005E20Rik (Trdn-as), in DCM. Our results revealed the remarkably upregulation of Trdn-as in the hearts of the DCM mice and cardiomyocytes treated with high glucose (HG). Knocking down Trdn-as in cardiac tissues significantly improved cardiac dysfunction and remodeling in the DCM mice. Conversely, Trdn-as overexpression resulted in cardiac damage resembling that observed in the DCM mice. At the cellular level, Trdn-as induced Ca²⁺ overload in the SR and mitochondria, leading to mitochondrial dysfunction. RNA-seq and bioinformatics analyses identified calsequestrin 2 (Casq2), a primary calcium-binding protein in the junctional SR, as a potential target of Trdn-as. Further investigations revealed that Trdn-as facilitated the recruitment of METTL14 to the Casq2 mRNA, thereby enhancing the m⁶A modification of Casq2. This modification increased the stability of Casq2 mRNA and subsequently led to increased protein expression. When Casq2 was knocked down, the promoting effects of Trdn-as on Ca²⁺ overload and mitochondrial damage were mitigated. These findings provide valuable insights into the pathogenesis of DCM and suggest Trdn-as as a potential therapeutic target for this condition.
Animals ; Diabetic Cardiomyopathies/pathology* ; RNA, Long Noncoding/genetics* ; Myocytes, Cardiac/metabolism* ; Mice ; Calsequestrin/genetics* ; Calcium/metabolism* ; Male ; Sarcoplasmic Reticulum/metabolism* ; Methyltransferases/metabolism* ; Mice, Inbred C57BL ; Mitochondria, Heart/metabolism* ; Disease Models, Animal ; Mitochondria/metabolism*

Chronic, unresolved inflammation correlates with persistent hepatic injury and fibrosis, ultimately progressing to hepatocellular carcinoma (HCC). Bisdemethoxycurcumin (BDMC) demonstrates therapeutic potential against HCC, yet its mechanism in preventing hepatic "inflammation-carcinoma transformation" remains incompletely understood. In the current research, clinical HCC specimens underwent analysis using hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC) to evaluate the expression of fibrosis markers, M2 macrophage markers, and CXCL12. In vitro, transforming growth factor-β1 (TGF-β1)-induced LX-2 cells and a co-culture system of LX-2, THP-1, and HCC cells were established. Cell functions underwent assessment through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and Transwell assays. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting and immunofluorescence evaluated the differential expression of molecules. The interaction between β-catenin/TCF4 and CXCL12 was examined using co-immunoprecipitation (Co-IP), dual luciferase, and chromatin immunoprecipitation (ChIP) assays. A DEN-induced rat model was developed to investigate BDMC's role in liver fibrosis-associated HCC (LFAHCC) development in vivo. Our results showed that clinical HCC tissues exhibited elevated fibrosis and enriched M2 macrophages. BDMC delayed liver fibrosis progression to HCC in vivo. BDMC inhibited the inflammatory microenvironment induced by activated hepatic stellate cells (HSCs). Furthermore, BDMC suppressed M2 macrophage-induced fibrosis and HCC cell proliferation and metastasis. Mechanistically, BDMC repressed TCF4/β-catenin complex formation, thereby reducing CXCL12 transcription in LX-2 cells. Moreover, CXCL12 overexpression reversed BDMC's inhibitory effect on macrophage M2 polarization and its mediation of fibrosis, as well as HCC proliferation and metastasis. BDMC significantly suppressed LFAHCC development through CXCL12 in rats. In conclusion, BDMC inhibited LFAHCC progression by reducing M2 macrophage polarization through suppressing β-catenin/TCF4-mediated CXCL12 transcription.
Animals ; Liver Neoplasms/etiology* ; Humans ; Carcinoma, Hepatocellular/immunology* ; Liver Cirrhosis/complications* ; Macrophages/drug effects* ; Male ; Rats ; Chemokine CXCL12/genetics* ; Diarylheptanoids/pharmacology* ; Rats, Sprague-Dawley ; beta Catenin/genetics*

ObjectiveTo analyze the psychological resilience characteristics of visually impaired adolescents. MethodsFrom February to May, 2023, 13 visually impaired adolescents (average age of 16.5 years) from Nanjing Normal University of Special Education, Yangzhou Special Education School and Nanjing School for the Blind in Jiangsu, China were selected for semi-structured interviews with phenomenological method, and the interview data were sorted by theme analysis method. ResultsFour themes and twelve sub-themes were obtained; namely multiple sources of difficulties, including travel difficulties, learning difficulties, social difficulties and difficulties in daily life; need for external support, including insufficient family support, school support needs to be improved, need for peer support and insufficient social support; negative and positive adaptation coexist, including negative adaptation and positive adaptation; and negative coping and positive coping coexist, including positive coping and negative coping. ConclusionThe psychological resilience of visually impaired adolescents is characterized by multiple sources of difficulties, insufficient external support, coexistence of positive and negative adaptation, and coexistence of positive and negative coping. A joint family-school-society support system should be formed to reduce the source of their difficulties, and help them establish positive adaptation and positive coping methods, to enhance their psychological resilience.

ObjectiveTo discuss the effects of Cistanches Herba phenylethanoid glycosides （CHPhGs） on the intestinal mucosal barrier and gut microbiota in alcoholic liver disease （ALD） mice were discussed. MethodThe 36 C57BL/6N female mice were randomly divided normal group， normal group of CHPhGs， model group， and low， medium， and high-dose groups （175， 350， 700 mg·kg^-1） of CHPhGs， with six mice in each group. The ALD mouse model was built using Lieber-Decarli alcohol liquid feed. The normal group and low， medium， and high-dose groups of CHPhGs were given CHPhGs by gavage daily. Serum aspartate aminotransferase aminotransferase （ALT）， alanine aminotransferase （AST）， triglycerides （TG）， and total cholesterol （TC） levels were detected by an automatic biochemical analyzer. Serum tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， lipopolysaccharide （LPS）， lipopolysaccharide-binding protein （LBP）， D-lactic acid （D-LA）， diamine oxidase （DAO）， and LBP of liver were detected by enzyme-linked immunosorbent assay （ELISA）. The levels of TG and TC in the liver were detected by colorimetry. Liver tissue was treated by oil red O and hematoxylin-eosin （HE） staining. The microstructure of jejunum epithelial cells was observed by electron microscope. Jejunum and colon were treated by HE staining and alcian blue-periodate-scheff (AB-PAS) staining staining， and mucin 2 （Muc2） was treated by immunohistochemistry. The intestinal contents of the normal group， normal group of CHPhGs， model group， and high-dose group of CHPhGs were collected and sequenced. ResultThe ALD model was established successfully. Compared with the normal group， the levels of serum ALT， AST， and TG， as well as the levels of liver TG and TC in the model group were significantly increased （P<0.05）. Histopathology showed that compared with the normal group， the liver cells in the model group showed obvious steatosis. Compared with the model group， the levels of serum TG and liver TG and TC in the low， medium， and high-dose groups of CHPhGs decreased significantly （P<0.05）. The serum ALT， AST， TNF-α， IL-1β， LPS， and LBP in the high-dose group of CHPhGs were also significantly decreased （P<0.05）. The number of liver cells with steatosis in the high-dose group of CHPhGs was significantly reduced， and the microvilli structure of jejunum epithelial cells was basically intact. The expression of Muc2 was reduced in the colon， and the gut microbiota of the high-dose group of CHPhGs changed significantly （P<0.05）. Compared with the normal group， the Allobaculum was significantly up-regulated in the model group （P<0.05）. Compared with the model group， the abundance of Akkermansia in the high-dose group of CHPhGs was significantly increased （P<0.01）. The abundance of Akkermansia was negatively correlated with that of Allobaculum （r=-0.701， P<0.01）. ConclusionCHPhGs can reduce the intestinal barrier injury caused by ALD， which may play a protective role by regulating the abundance and structure of Akkermansia and Allobaculum and affecting the homeostasis of intestinal mucus.

Melanoma is a malignant skin tumor characterized by a propensity for early metastasis and high mortality rates. Immune checkpoint inhibitors have significantly improved the prognosis for melanoma patients, however, some individuals remain unresponsive to immunotherapy, primarily due to the immunosuppressive characteristics of the tumor microenvironment. This review summarizes recent research on the melanoma tumor microenvironment and analyzes how dynamic changes in its components influence melanoma development and the efficacy of immunotherapy. Additionally, it outlines immunotherapy strategies focused on immune checkpoint inhibitors, examines their mechanisms of action and limitations, and further investigates the effects of combining immune checkpoint inhibitors with various therapeutic modalities, including radiotherapy, chemotherapy, and targeted therapies. This study aims to provide new insights into the melanoma tumor microenvironment and the advancement of personalized precision immunotherapy.

Background::The potential impact of pre-existing coronary artery stenosis (CAS) on acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and the elevation of high-sensitivity cardiac troponin I (hs-cTnI) levels in patients with PE.Methods::In this multicenter, prospective case-control study, 88 cases and 163 controls matched for age, sex, and study center were enrolled. Cases were patients with PE with elevated hs-cTnI. Controls were patients with PE with normal hs-cTnI. Coronary artery assessment utilized coronary computed tomographic angiography or invasive coronary angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression was used to evaluate the association between CAS and hs-cTnI elevation.Results::The percentage of CAS was higher in the case group compared to the control group (44.3% [39/88] vs. 30.1% [49/163]; P = 0.024). In multivariable conditional logistic regression model 1, CAS (adjusted odds ratio [OR], 2.680; 95% confidence interval [CI], 1.243–5.779), heart rate >75 beats/min (OR, 2.306; 95% CI, 1.056–5.036) and N-terminal pro-B type natriuretic peptide (NT-proBNP) >420 pg/mL (OR, 12.169; 95% CI, 4.792–30.900) were independently associated with elevated hs-cTnI. In model 2, right CAS (OR, 3.615; 95% CI, 1.467–8.909) and NT-proBNP >420 pg/mL (OR, 13.890; 95% CI, 5.288–36.484) were independently associated with elevated hs-cTnI. Conclusions::CAS was independently associated with myocardial injury in patients with PE. Vigilance towards CAS is warranted in patients with PE with elevated cardiac troponin levels.

Objective To investigate the predictive value of serum Actinin-4 and N-myc downscream regu-lated gene 4(NDRG4)for recurrence and metastasis in early stage lung cancer patients.Methods A total of 110 patients who underwent early lung cancer radical surgery in the hospital from January 2020 to January 2022 were collected as the study subjects.They were separated into a recurrence group of 62 patients and a non recurrence group of 48 patients based on whether they experienced recurrence or metastasis during a one-year follow-up.Enzyme-linked immunosorbnent assay(ELISA)method was applied to detect serum Actinin-4 and NDRG4 levels.Pearson and Spearman methods were used for correlation analysis.Logistic regression was applied to analyze the influencing factors of recurrence and metastasis in early stage lung cancer patients after radical surgery.Receiver operating characteristic(ROC)curve was applied to analyze the predictive value of serum Actinin-4 and NDRG4 levels for recurrence and metastasis in early stage lung cancer patients after radi-cal surgery.Results Compared with the non recurrence group,the serum Actinin-4 level in the recurrence group was obviously increased,while the NDRG4 level was obviously reduced,and there was a obvious differ-ence in TNM staging and lymph node metastasis between the two groups(P＜0.05).Pearson analysis showed that there was a negative correlation between serum Actinin-4 and NDRG4 levels in the recurrence group(r=-0.566,P＜0.05).Spearman analysis showed that Actinin-4 was positively correlated with lymph node me-tastasis and clinical staging(r=0.429,0.396,P＜0.05),while NDRG4 was negatively correlated with lymph node metastasis and clinical staging(r=-0.411,-0.431,P＜0.05).Logistic regression analysis showed that lymph node metastasis,clinical staging,Actinin-4,and NDRG4 levels could all be used as influencing fac-tors for postoperative recurrence and metastasis in early stage lung cancer patients after radical surgery(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of serum Actinin-4 and NDRG4 in predicting postoperative recurrence and metastasis in early stage lung cancer patients after radical surgery was 0.857 and 0.848,respectively,and the AUC of combined prediction was 0.950,which was better than those of the two single predictions(P＜0.05).Conclusion Serum Actinin-4 level increases and NDRG4 level decrea-ses in early stage lung cancer patients with postoperative recurrence and metastasis after radical surgery.The combined detection of the two could serve as an auxiliary indicator for predicting postoperative recurrence and metastasis in early stage lung cancer patients after radical surgery.

Melanoma is a malignant skin tumor characterized by a propensity for early metastasis and high mortality rates. Immune checkpoint inhibitors have significantly improved the prognosis for melanoma patients, however, some individuals remain unresponsive to immunotherapy, primarily due to the immunosuppressive characteristics of the tumor microenvironment. This review summarizes recent research on the melanoma tumor microenvironment and analyzes how dynamic changes in its components influence melanoma development and the efficacy of immunotherapy. Additionally, it outlines immunotherapy strategies focused on immune checkpoint inhibitors, examines their mechanisms of action and limitations, and further investigates the effects of combining immune checkpoint inhibitors with various therapeutic modalities, including radiotherapy, chemotherapy, and targeted therapies. This study aims to provide new insights into the melanoma tumor microenvironment and the advancement of personalized precision immunotherapy.