Doxorubicin (DOX)-induced cardiotoxicity and sepsis-induced myocardial injury (SIMI) represent significant clinical challenges in patients undergoing chemotherapy, sharing a common pathological basis of oxidative stress and mitochondrial dysfunction. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has recently been shown to play a critical role in DOX-induced cardiotoxicity and lipopolysaccharide (LPS)-induced SIMI. This article systematically reviews the mechanisms underlying myocardial injury caused by DOX and sepsis, identifying ferroptosis as a central common pathway. DOX triggers a burst of reactive oxygen species within mitochondria and inhibits glutathione peroxidase 4 (GPX4) activity through redox cycling of its quinone group and high-affinity accumulation in mitochondrial cardiolipin. LPS, by activating pattern recognition receptors and related inflammatory signaling pathways, provokes a cytokine storm and mitochondrial dysfunction. Both can disrupt the core regulatory axis of cysteine-glutathione (GSH)-GPX4, synergistically promoting ferroptosis in cardiomyocytes. Moreover, epigenetic regulation plays a key role in DOX- and LPS-induced cardiomyocyte ferroptosis and may serve as a promising therapeutic target. A deeper understanding of the ferroptosis mechanism and its epigenetic regulatory network in the synergistic injury induced by DOX and sepsis is of great importance for developing novel strategies to mitigate chemotherapy-related cardiotoxicity and improve outcomes in cancer patients with concurrent infections.

Circulating fetal cells have been proven to contain complete cellular structures and comprehensive fetal genome information, enabling non-invasive prenatal diagnosis of aneuploidy diseases, chromosomal microdeletions, and monogenic diseases. However, due to the low abundance of these rare fetal cells in maternal peripheral blood, their isolation and detection remains challenging. In recent years, novel isolation and enrichment techniques, such as microfluidic technologies and novel nanomaterials, for circulating fetal cells enrichment have been continuously advancing.This review provides a comprehensive summary of two novel methodologies for the isolation and enrichment of circulating fetal cells. Their separation principles, advantages, limitations, as well as the separation efficiencies will also be described.

Diabetic chronic wounds are characterized by difficult healing, recurrent progression, and high rates of disability and mortality, which make their clinical treatment a medical challenge urgent to be addressed. However, the complex local microenvironment conditions of chronic wounds, such as high protease activity and persistent inflammatory responses, result in low bioavailability of exogenous cytokines (e.g., chemokine CXCL12) at the wound site, limiting their clinical application. In this study, we utilized Lactobacillus plantarum WCFS1 as the chassis to develop an efficient CXCL12 delivery system based on synthetic biology. Subsequently, we evaluated the role of the engineered probiotic strain in promoting the chronic wound healing in diabetic mice. Firstly, we fused the endogenous secretion signal peptide lp_3050 (SP_{lp_3050}) of L. plantarum WCFS1 and the commonly used secretion signal peptide usp45 (SP_usp45) of lactic acid bacteria with the reporter gene gusA and inserted them into the pTRK892-P_32(pgm) plasmid by molecular cloning. Then, we prepared the engineered strains and characterized the efficacy of the two signal peptides in driving the secretion of GusA. The results showed that SP_{lp_3050} efficiently drove the secretion of GusA in L. plantarum WCFS1, increasing the activity of GusA in the culture supernatant by nearly five times compared with that of SP_{lp_3050}. Further, we fused SP_{lp_3050} and codon-optimized CXCL12 gene to construct an engineered probiotic strain Lpw-CXCL12 for CXCL12 delivery. The results demonstrated that the content of CXCL12 in the culture supernatant reached (13.40±0.20) μg/mL. Finally, we found that the engineered probiotic strain Lpw-CXCL12 accelerated chronic wound healing in a diabetic mouse model. In conclusion, these results support an engineered probiotic strain in promoting diabetic chronic wound healing, providing a new strategy and technological foundation for the management of diabetic chronic wounds in the future.
Probiotics ; Animals ; Chemokine CXCL12/biosynthesis* ; Mice ; Wound Healing ; Lactobacillus plantarum/metabolism* ; Diabetes Mellitus, Experimental/complications* ; Male

Objective To explore the application value of high-flow nasal oxygen therapy combined with non-invasive positive pressure ventilation in very low birth weight infants after weaning from invasive mechanical ventilation.Methods From February 2022 to May 2024,80 cases of very low birth weight infants who were weaned from invasive mechanical ventilation in Second Affiliated Hospital of Wenzhou Medical University were selected and divided into single ventilation group and combined oxygen therapy group according to the random number table method,with 40 cases in each group.Single ventilation group was intervened with non-invasive positive pressure ventilation,while combined oxygen therapy group was intervened with high-flow nasal oxygen therapy combined with non-invasive positive pressure ventilation.The disappearance time of clinical symptoms,the score of neonatal behavioral neurological assessment(NBNA),vitamin D and blood gas indicators of two groups of premature infants were compared.And the degree of broncho pulmonary dysplasia(BPD)in premature infants was evaluated.Results The disappearance time of clinical symptoms,non-invasive positive pressure ventilation time and total oxygen requirement time of preterm infants in combined oxygen therapy group were significantly shorter than those in single ventilation group(P＜0.05).After 14 days of intervention,the NBNA scores,vitamin D,oxygenation index and blood oxygen saturation of premature infants in both groups were significantly higher than those before intervention in this group(P＜0.05).The NBNA score,vitamin D,oxygenation index and blood oxygen saturation of preterm infants in combined oxygen therapy group were significantly higher than those in single ventilation group(P＜0.05).The degree of BPD in combined oxygen therapy group was significantly milder than that in single ventilation group(x2=8.571,P=0.003).Conclusion After weaning from invasive mechanical ventilation in very low birth weight infants,high-flow nasal oxygen therapy combined with non-invasive positive pressure ventilation intervention can help reduce inflammatory responses and brain damage,improve blood gas indicators,and lower the degree of BPD.

ObjectiveTo investigate the accuracy of multiple discriminant analysis （MDA） versus fibrosis-4 （FIB-4） in assessing liver fibrosis degree in patients with HBV infection， as well as the possibility of MDA as an indicator for disease progression. MethodsA total of 263 patients with HBV infection who underwent liver biopsy in The First Affiliated Hospital of Guangxi Medical University from April 2010 to April 2024 were included， and their clinical data were collected. According to the results of pathological examination， they were divided into non-significant fibrosis group （F<2） with 126 patients and significant fibrosis group （F≥2） with 137 patients. The correlation of MDA and FIB-4 with liver fibrosis degree was analyzed， and MDA and FIB-4 were compared in terms of their accuracy in assessing significant liver fibrosis. A total of 62 patients completed follow-up， and according to the presence or absence of progression to liver cirrhosis at the last follow-up visit， they were divided into progressive group with 21 patients and non-progressive group with 41 patients； the efficacy of MDA and FIB-4 in diagnosing disease progression was analyzed and compared. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups； the Kruskal-Wallis H test was used for comparison between multiple groups， and the Bonferroni method was used for further comparison between two groups. The chi-square test was used for comparison of categorical data. The Spearman’s correlation coefficient was used for correlation analysis. The Wilcoxon signed rank sum test was used for the analysis of baseline data and data at the end of follow-up， and the binary Logistic regression analysis was used to investigate the influencing factors for progression to liver cirrhosis. The receiver operating characteristic （ROC） curve was used to investigate the diagnostic efficacy of indicators， the Z-test was used for comparison of the area under the ROC curve （AUC）， and the paired chi-square test was used for comparison of the sensitivity， specificity， and accuracy of the two indicators. ResultsThe correlation coefficient between FIB-4 and liver fibrosis degree was 0.378， while the correlation coefficient between MDA and liver fibrosis degree was -0.325 （both P<0.001）. FIB-4 had an AUC of 0.688， a sensitivity of 64.96%， a specificity of 68.87%， a positive predictive value of 67.42%， a negative predictive value of 63.36%， an accuracy of 65.40%， and a cut-off value of 1.01， while MDA had an AUC of 0.653， a sensitivity of 52.55%， a specificity of 78.57%， a positive predictive value of 72.73%， a negative predictive value of 60.37%， an accuracy of 65.02%， and a cut-off value of 0.29， suggesting that compared with FIB-4， MDA had a lower sensitivity （P=0.004） and a higher specificity （P=0.001）. The progressive group had a significantly higher age than the non-progressive group at baseline （t=2.611， P=0.011）. For the progressive group， there was an increase in FIB-4 and a reduction in MDA from baseline to the end of follow-up （both P<0.001）， while the non-progressive group showed no significant changes （both P>0.05）. The multivariate Logistic regression analysis showed that aspartate aminotransferase （odds ratio ［OR］=0.940， 95% confidence interval ［CI］： 0.885‍ ‍—‍ ‍0.998， P<0.05） and MDA （OR=0.445， 95%CI： 0.279‍ ‍—‍ ‍0.710， P<0.001） were independent influencing factors for disease progression. MDA had an AUC of 0.893 and an optimal cut-off value of -0.01 in diagnosing the disease progression of liver cirrhosis. ConclusionMDA has a comparable accuracy to FIB-4 in the diagnosis of significant liver fibrosis， and MDA<-0.01 has a high accuracy in diagnosing the progression of liver fibrosis to liver cirrhosis， which can help to reduce the need for liver biopsy in clinical practice.

[Objective]To explore the relationships between the specifications of pills and medication and syndrome treatment in Jingui Yaolue,summarize ZHANG Zhongjing's academic thoughts of flexibly using pills.[Methods]Through studying Jingui Yaolue,combining the annotations of past generations and modern researches,this study summarized the specifications of the pills involved in the whole book based on the"quantity",interpreted the meaning of the specifications,analyzed the selection basis of different pill specifications from the two dimensions of medication and syndrome treatment,and summarized the academic thoughts of pills and its modern clinical significance.[Results]ZHANG Zhongjing established a two-dimensional specification system of"size-amount"of pills.The size of the pill was standardized by the quantitative unit and the amount of medicine was determined according to the single dosage and the frequency of medication.He emphasized that the amount of medicine was led through medication,paid attention to the unification of"medicinal properties-medicine quantity"and the balance of efficacy and poison.Moreover,he advocated clarifying the amount according to the syndrome treatment,flexibly adjusted the specifications of pills in terms of medicinal methods,objects and time of taking,and built a dynamic balance system of"specifications-medicine efficacy".This academic thoughts of using pills was based on specifications and deeply guided modern clinical practice.[Conclusion]ZHANG Zhongjing's academic thoughts of using pills takes"amount"as the core realized the unification of individualized medication and maximum therapeutic effect through specification selection.Based on the specifications of pills,focusing on"amount-effect"research,and integrating modern research results,it was expected to provide more accurate guidance for the clinical application of pills and promote its modern application.

[Objective]To explore the relationships between the specifications of pills and medication and syndrome treatment in Jingui Yaolue,summarize ZHANG Zhongjing's academic thoughts of flexibly using pills.[Methods]Through studying Jingui Yaolue,combining the annotations of past generations and modern researches,this study summarized the specifications of the pills involved in the whole book based on the"quantity",interpreted the meaning of the specifications,analyzed the selection basis of different pill specifications from the two dimensions of medication and syndrome treatment,and summarized the academic thoughts of pills and its modern clinical significance.[Results]ZHANG Zhongjing established a two-dimensional specification system of"size-amount"of pills.The size of the pill was standardized by the quantitative unit and the amount of medicine was determined according to the single dosage and the frequency of medication.He emphasized that the amount of medicine was led through medication,paid attention to the unification of"medicinal properties-medicine quantity"and the balance of efficacy and poison.Moreover,he advocated clarifying the amount according to the syndrome treatment,flexibly adjusted the specifications of pills in terms of medicinal methods,objects and time of taking,and built a dynamic balance system of"specifications-medicine efficacy".This academic thoughts of using pills was based on specifications and deeply guided modern clinical practice.[Conclusion]ZHANG Zhongjing's academic thoughts of using pills takes"amount"as the core realized the unification of individualized medication and maximum therapeutic effect through specification selection.Based on the specifications of pills,focusing on"amount-effect"research,and integrating modern research results,it was expected to provide more accurate guidance for the clinical application of pills and promote its modern application.

Objective To explore the application value of high-flow nasal oxygen therapy combined with non-invasive positive pressure ventilation in very low birth weight infants after weaning from invasive mechanical ventilation.Methods From February 2022 to May 2024,80 cases of very low birth weight infants who were weaned from invasive mechanical ventilation in Second Affiliated Hospital of Wenzhou Medical University were selected and divided into single ventilation group and combined oxygen therapy group according to the random number table method,with 40 cases in each group.Single ventilation group was intervened with non-invasive positive pressure ventilation,while combined oxygen therapy group was intervened with high-flow nasal oxygen therapy combined with non-invasive positive pressure ventilation.The disappearance time of clinical symptoms,the score of neonatal behavioral neurological assessment(NBNA),vitamin D and blood gas indicators of two groups of premature infants were compared.And the degree of broncho pulmonary dysplasia(BPD)in premature infants was evaluated.Results The disappearance time of clinical symptoms,non-invasive positive pressure ventilation time and total oxygen requirement time of preterm infants in combined oxygen therapy group were significantly shorter than those in single ventilation group(P＜0.05).After 14 days of intervention,the NBNA scores,vitamin D,oxygenation index and blood oxygen saturation of premature infants in both groups were significantly higher than those before intervention in this group(P＜0.05).The NBNA score,vitamin D,oxygenation index and blood oxygen saturation of preterm infants in combined oxygen therapy group were significantly higher than those in single ventilation group(P＜0.05).The degree of BPD in combined oxygen therapy group was significantly milder than that in single ventilation group(x2=8.571,P=0.003).Conclusion After weaning from invasive mechanical ventilation in very low birth weight infants,high-flow nasal oxygen therapy combined with non-invasive positive pressure ventilation intervention can help reduce inflammatory responses and brain damage,improve blood gas indicators,and lower the degree of BPD.

Circulating fetal cells have been proven to contain complete cellular structures and comprehensive fetal genome information, enabling non-invasive prenatal diagnosis of aneuploidy diseases, chromosomal microdeletions, and monogenic diseases. However, due to the low abundance of these rare fetal cells in maternal peripheral blood, their isolation and detection remains challenging. In recent years, novel isolation and enrichment techniques, such as microfluidic technologies and novel nanomaterials, for circulating fetal cells enrichment have been continuously advancing.This review provides a comprehensive summary of two novel methodologies for the isolation and enrichment of circulating fetal cells. Their separation principles, advantages, limitations, as well as the separation efficiencies will also be described.

ObjectiveTo investigate the performance of fibrosis-4 （FIB-4） versus aspartate aminotransferase-to-platelet ratio index （APRI） in predicting advanced liver fibrosis and disease progression in patients with chronic HBV infection. MethodsA total of 497 patients with chronic HBV infection who underwent liver biopsy in The First Affiliated Hospital of Guangxi Medical University from February 2013 to December 2022 were enrolled， among whom 404 were enrolled in a retrospective study and 75 were enrolled in a prospective study. Related indicators were collected， including demographic features （sex and age）， biochemical indices （alanine aminotransferase ［ALT］ and aspartate aminotransferase ［AST］）， and platelet count， and FIB-4 and APRI were calculated. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups； the chi-square test was used for comparison of categorical data between groups. The area under the ROC curve （AUC） was used to assess the ability of APRI and FIB-4 in evaluating liver fibrosis degree and disease progression in patients with chronic HBV infection. ResultsIn the retrospective analysis， compared with the FIB-4<2.67 group， the FIB-4≥2.67 group had a significantly higher proportion of the patients who were diagnosed with liver cirrhosis or hepatocellular carcinoma （66.19% vs 47.54%， χ²=12.75， P<0.001）. The medians of FIB-4 and APRI increased significantly with liver fibrosis degree from F0 to F4 （H=42.5 and 35.9， both P<0.001）. As for the fibrosis stage of F0-F4， the median of FIB-4 was significantly higher than that of APRI in the patients with the same fibrosis stage （H=59.71， P<0.001）. FIB-4 and APRI had a similar AUC for predicting stage F3 fibrosis （0.67 vs 0.65， Z=0.71， P=0.480）， while FIB-4 had a higher AUC for predicting stage F4 fibrosis than APRI （0.72 vs 0.64， Z=10.50， P<0.001）. In the prospective study cohort， FIB-4 and APRI showed an increasing trend over time in predicting disease progression （chronic hepatitis B to liver cirrhosis）， with an AUC of 0.718 （95% confidence interval ［CI］： 0.476‍ ‍—‍ ‍0.760） and 0.555 （95%CI： 0.408‍ ‍—‍ ‍0.703）， respectively， and FIB-4 had a significantly higher accuracy than APRI in predicting disease progression （χ²=12.44， P<0.001）. ConclusionFIB-4 and APRI can be used to evaluate advanced liver fibrosis （F3 and F4） and predict disease progression， and FIB-4 is superior to APRI in certain aspects.