Hepatocellular carcinoma （HCC） is a malignant tumor with relatively high incidence and mortality rates worldwide， and its therapeutic resistance and recurrence mechanism are closely associated with liver cancer stem cells （LCSC）. This article systematically introduces the biological characteristics of LCSC and their key role in the progression of HCC， reviews the functional characteristics of the specific surface markers （such as EpCAM and CD133） and related signaling pathways （such as Wnt/β-catenin， TGF-β， and STAT3）， elaborates on the interaction between LCSC and tumor microenvironment， and summarizes the latest clinical treatment strategies targeting LCSC and the countermeasure for existing resistance mechanisms. The article points out that LCSC promote tumor development and progression through metabolic reprogramming and immune microenvironment remodeling， and it is proposed to establish a standardized detection system for LCSC specific markers and promote a triple synergistic therapeutic paradigm combining targeted therapy， immune regulation， and traditional chemotherapy， in order to provide new ideas for the clinical intervention of HCC.

Liver cirrhosis is the final stage of the progression of various chronic liver diseases， often accompanied by serious complications and high mortality rates. Recent studies have shown that the interaction between gut microbiota and bile acid metabolism （the gut microbiota-bile acid axis） is closely associated with liver cirrhosis. This article systematically reviews the mechanism of action of the gut microbiota-bile acid axis in the progression of liver cirrhosis， elaborates on the pathological features of liver cirrhosis and its harm to the body， and summarizes the association of the gut microbiota-bile acid axis with the development and progression of liver cirrhosis. It also analyzes the key regulatory role of this axis in the progression of liver cirrhosis and explores its potential application value as a therapeutic target for liver cirrhosis， in order to provide a theoretical basis for exploring more effective clinical intervention methods.

Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

Objective To investigate the current status of breastfeeding motivation in early post-partum women and analyze the influencing factors of breastfeeding motivation.Methods A conven-ience sampling method was used to select 205 hospitalized women within 48 to 72 hours postpartum as the study subjects.The women were surveyed using a general information questionnaire,a breastfeed-ing motivation scale,a breastfeeding knowledge questionnaire,and a short-form scale for breastfeed-ing self-efficacy.Multiple linear regression analysis was conducted to explore the influencing factors of breastfeeding motivation among the women.Results The average score for autonomous motivation to-wards breastfeeding among 205 women was(49.94±7.62),and the average score for controlled mo-tivation was(23.76±3.59).The results of multiple linear regression analysis showed that age,par-ticipation in breastfeeding-related courses during pregnancy,planned duration of breastfeeding,skill dimension score of the short-form scale for breastfeeding self-efficacy,and total score on the breast-feeding knowledge questionnaire were influencing factors for the autonomous motivation score towards breastfeeding(P＜0.05);participation in breastfeeding-related courses during pregnancy,skill di-mension score on the short-form breastfeeding self-efficacy,and total score on the breastfeeding knowledge questionnaire were influencing factors for the controlled motivation score towards breast-feeding(P＜0.05).Conclusion The level of breastfeeding motivation in early postpartum women needs to be improved.Healthcare providers should focus on maternal age and planned duration of breastfeeding,strengthen breastfeeding knowledge education,and enhance maternal breastfeeding self-efficacy to improve maternal breastfeeding motivation and breastfeeding rates.

Peroxynitrite anion(ONOO-),which is originated from the reaction of nitric oxide(NO)and superoxide anion(O2-),plays a pivotal role in immune defense and signal regulation.Excessive levels of ONOO-may induce the occurrence of various diseases such as Alzheimer's disease,inflammation,cardiovascular disease and cancer,etc.Existing detection methods for ONOO-have limitations such as complexity,time consumption,and low cell biocompatibility.In this study,a novel fluorescent probe QFPD was developed using quinoline and diphenylphosphinamide as fluorescent keleton and recognition group,respectively.The strong oxidizing property of ONOO-triggerd the cleavage of phosphoramide bond,leading to fluorescence quenching and a visible color change of the solution from yellow to purple,thereby enabling"ON-OFF"type recognition of ONOO-.QFPD exhibited excellent characteristics including good selectivity and high sensitivity in fluorescence detection(Limit of detection of 1.37 μmol/L),large Stokes shift(130 nm),rapid response(10 min),and strong anti-interference ability.Additionally,QFPD demonstrated good biocompatibility and could realize real-time dynamic monitoring of endogenous ONOO-.Furthermore,QFPD was successfully applied to environmental toxicology research by visualizing the oxidative stress effects induced by microplastics polymethyl methacrylate(PMMA)and Hg2+exposure,which might be a novel tool for the mechanism research on oxidative stress associated with microplastic pollution and heavy metal exposure.

AIM To explore the clinical effects of Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation on patients with mild to moderate bronchial asthma in chronic and persistent period.METHODS One hundred and eighteen patients were randomly assigned into control group(59 cases)for 4-week administration of Budesonide and Formoterol Fumarate Powder for Inhalation,and observation group(59 cases)for 4-week administration of both Jiawei Yanghe Decoction and Budesonide and Formoterol Fumarate Powder for Inhalation.The changes in clinical effects,ACT score,bronchial asthma control rate,pulmonary function indices(FEV1,PEF,FEV1％,PEF％),inflammatory indices(EOS,EOS％,FeNO),TCM syndrome score and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed increased bronchial asthma control rate,ACT score,PEF(P＜0.05),and decreased TCM syndrome score(P＜0.05),especially for the observation group(P＜0.05);the observation group exhibited increased FEV1,FEV1％,PEF％(P＜0.05),among which FEV1,PEF％were higher than those in the control group(P＜0.05);the observation group showed decreased inflammatory indices(P＜0.05),among which FeNO was lower than that in the control group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with mild to moderate bronchial asthma in chronic and persistent period,Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation can safely and effectively alleviate clinical symptoms,improve pulmonary functions,airway inflammatory reactions,and enhance bronchial asthma control rate.

Objective:To investigate the effect of COX6C on the proliferation of multiple myeloma(MM)cells and its mechanism of action.Methods:The expression of COX6C in MM cell lines were detected by RT-PCR.siRNA technology was used to knockdown COX6C expression in OPM2 cells.MTT assay and flow cytometry were employed to assess the effect of COX6C knockdown by siRNA on cell proliferation,mitochondrial membrane potential(Δ Ψm),and intracellular adenosine triphosphate(ATP)levels.The mitochondrial morphological changes in OPM2 cells pre-and post-siRNA-mediated COX6C knockdown were observed by transmission electron microscopy(TEM).Results:The relative expression level of COX6C was significantly increased in MM cell lines(P＜0.01).Following siRNA-mediated COX6C knockdown,OPM2 cell proliferation was inhibited,with viable cells accounting for 62.32％±3.43％and 47.01％±5.12％after 48 and 72 hours of culture,respectively.siRNA-mediated COX6C knockdown also caused significant reductions in mitochondrial membrane potential and intracellular ATP levels(P＜0.05),accompanied by mitochondrial shortening,swelling,and incomplete cristae structures.Conclusion:COX6C may promote the proliferation of MM cells by altering the mitochondrial structure and elevating intracellular ATP levels.

Objective:To investigate the effect of COX6C on the proliferation of multiple myeloma(MM)cells and its mechanism of action.Methods:The expression of COX6C in MM cell lines were detected by RT-PCR.siRNA technology was used to knockdown COX6C expression in OPM2 cells.MTT assay and flow cytometry were employed to assess the effect of COX6C knockdown by siRNA on cell proliferation,mitochondrial membrane potential(Δ Ψm),and intracellular adenosine triphosphate(ATP)levels.The mitochondrial morphological changes in OPM2 cells pre-and post-siRNA-mediated COX6C knockdown were observed by transmission electron microscopy(TEM).Results:The relative expression level of COX6C was significantly increased in MM cell lines(P＜0.01).Following siRNA-mediated COX6C knockdown,OPM2 cell proliferation was inhibited,with viable cells accounting for 62.32％±3.43％and 47.01％±5.12％after 48 and 72 hours of culture,respectively.siRNA-mediated COX6C knockdown also caused significant reductions in mitochondrial membrane potential and intracellular ATP levels(P＜0.05),accompanied by mitochondrial shortening,swelling,and incomplete cristae structures.Conclusion:COX6C may promote the proliferation of MM cells by altering the mitochondrial structure and elevating intracellular ATP levels.

AIM To explore the clinical effects of Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation on patients with mild to moderate bronchial asthma in chronic and persistent period.METHODS One hundred and eighteen patients were randomly assigned into control group(59 cases)for 4-week administration of Budesonide and Formoterol Fumarate Powder for Inhalation,and observation group(59 cases)for 4-week administration of both Jiawei Yanghe Decoction and Budesonide and Formoterol Fumarate Powder for Inhalation.The changes in clinical effects,ACT score,bronchial asthma control rate,pulmonary function indices(FEV1,PEF,FEV1％,PEF％),inflammatory indices(EOS,EOS％,FeNO),TCM syndrome score and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed increased bronchial asthma control rate,ACT score,PEF(P＜0.05),and decreased TCM syndrome score(P＜0.05),especially for the observation group(P＜0.05);the observation group exhibited increased FEV1,FEV1％,PEF％(P＜0.05),among which FEV1,PEF％were higher than those in the control group(P＜0.05);the observation group showed decreased inflammatory indices(P＜0.05),among which FeNO was lower than that in the control group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with mild to moderate bronchial asthma in chronic and persistent period,Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation can safely and effectively alleviate clinical symptoms,improve pulmonary functions,airway inflammatory reactions,and enhance bronchial asthma control rate.

Purpose::Vibrio vulnificus ( V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body's infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistant V. Vulnificus and the protection of their vital organs. Methods::An increasing concentration gradient method was used to induce multidrug-resistant V. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistant V. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues and in human hepatocellular carcinomas-2 and human kidney-2 cell lines was used to evaluate the effect of bergamottin on the nuclear factor kappa-B signaling pathway. One-way ANOVA and Kaplan-Meier analysis were used for statistical analysis. Results::In mice infected with multidrug-resistant V. Vulnificus, bergamottin prolonged survival ( p = 0.014), reduced the serum creatinine ( p = 0.002), urea nitrogen ( p = 0.030), aspartate aminotransferase ( p = 0.029), and alanine aminotransferase ( p = 0.003) levels, and protected the cellular morphology of liver and kidney tissues. Bergamottin inhibited interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α expression in serum (IL-1β: p = 0.010, IL-6: p = 0.029, TNF-α: p = 0.025) and inhibited the protein expression of the inflammatory factors IL-1β, IL-6, TNF-α in liver (IL-1β: p = 0.010, IL-6: p = 0.011, TNF-α: p = 0.037) and kidney (IL-1β: p = 0.016, IL-6: p = 0.011, TNF-α: p = 0.008) tissues. Bergamottin did not affect the proliferation of multidrug-resistant V. Vulnificus or the bacterial load in the mouse peritoneal lavage fluid ( p = 0.225), liver ( p = 0.186), or kidney ( p = 0.637). Conclusion::Bergamottin enhances the tolerance of mice to multidrug-resistant V. Vulnificus infection. This study can serve as a reference and guide the development of novel clinical treatment strategies for V. Vulnificus.