Cuproptosis and ferroptosis， two recently identified metal ion-dependent forms of cell death， are triggered by homeostasis dysregulation of intracellular copper and iron， as well as oxidative stress. They demonstrate considerable potential in anti-tumor therapy. Cuproptosis arises from mitochondrial dysfunction and proteotoxic stress caused by copper overload， while ferroptosis is driven by iron-dependent lipid peroxidation. Although traditional Chinese medicine （TCM） exhibits regulatory effects on cuproptosis and ferroptosis， its clinical application is hindered by poor solubility and low bioavailability. Through physical nanonization or carrier-based delivery technologies adopted by nano-TCM， the targeting specificity， stability， and bioavailability of drugs are significantly improved. By integrating sustained-release and controlled-release properties， metal ion homeostasis and redox balance in the tumor microenvironment （TME） can be precisely modulated. Research demonstrates that nano-TCM， such as celastrol-copper nanocomplexes （Cel-Cu NPs）， induces cuproptosis by augmenting intracellular copper accumulation and suppressing glutathione （GSH） levels. Nano-systems encapsulating camptothecin or artemisinin trigger ferroptosis via Fenton reaction and GSH depletion. Synergistic strategies of nano-materials， including ferrum-based metal-organic frameworks （Fe-MOFs） combined with piperlongumine， further amplify antitumor efficacy. Despite advancements in targeting cuproptosis and ferroptosis， challenges persist in nano-TCM development， including complex fabrication processes， suboptimal dosage optimization， and insufficient integration with the holistic principles of TCM. Future research should focus on exploring the interaction between cuproptosis and ferroptosis， developing multi-targeted nanodelivery systems， and fostering deeper integration of TCM theory with nanomedicine to advance novel therapeutic strategies for oncology.

Cuproptosis and ferroptosis， two recently identified metal ion-dependent forms of cell death， are triggered by homeostasis dysregulation of intracellular copper and iron， as well as oxidative stress. They demonstrate considerable potential in anti-tumor therapy. Cuproptosis arises from mitochondrial dysfunction and proteotoxic stress caused by copper overload， while ferroptosis is driven by iron-dependent lipid peroxidation. Although traditional Chinese medicine （TCM） exhibits regulatory effects on cuproptosis and ferroptosis， its clinical application is hindered by poor solubility and low bioavailability. Through physical nanonization or carrier-based delivery technologies adopted by nano-TCM， the targeting specificity， stability， and bioavailability of drugs are significantly improved. By integrating sustained-release and controlled-release properties， metal ion homeostasis and redox balance in the tumor microenvironment （TME） can be precisely modulated. Research demonstrates that nano-TCM， such as celastrol-copper nanocomplexes （Cel-Cu NPs）， induces cuproptosis by augmenting intracellular copper accumulation and suppressing glutathione （GSH） levels. Nano-systems encapsulating camptothecin or artemisinin trigger ferroptosis via Fenton reaction and GSH depletion. Synergistic strategies of nano-materials， including ferrum-based metal-organic frameworks （Fe-MOFs） combined with piperlongumine， further amplify antitumor efficacy. Despite advancements in targeting cuproptosis and ferroptosis， challenges persist in nano-TCM development， including complex fabrication processes， suboptimal dosage optimization， and insufficient integration with the holistic principles of TCM. Future research should focus on exploring the interaction between cuproptosis and ferroptosis， developing multi-targeted nanodelivery systems， and fostering deeper integration of TCM theory with nanomedicine to advance novel therapeutic strategies for oncology.

ObjectiveTo systematically review the association between non-alcoholic fatty liver disease （NAFLD） and depression， and to provide a basis for synergistic management in clinical practice. MethodsThis study was conducted according to the PRISMA guidelines， with the PROSPERO registration number of CRD42023482013. PubMed， Embase， the Cochrane Library， Web of Science， CNKI， Wanfang Data， VIP， and CBM were searched for articles on the association between NAFLD and depression published up to November 1， 2024. The articles were screened according to the inclusion and exclusion criteria， and related data were extracted. RevMan 5.3 was used to perform the Meta-analysis. ResultsA total of 18 studies were included， involving 396 793 participants. Among these studies， 12 discussed the influence of NAFLD on depression， involving 224 269 participants， among whom there were 75 574 patients with NAFLD. The Meta-analysis showed that NAFLD was significantly associated with the risk of depression （odds ratio ［OR］=1.21， 95% confidence interval ［CI］： 1.12 — 1.30， P0.001）. Six studies examined the influence of depression on NAFLD， involving 172 524 participants， among whom there were 29 368 patients with depression. The meta-analysis showed that depression caused a significant increase in the risk of NAFLD （OR=1.13， 95%CI： 1.05 — 1.22， P=0.001）. ConclusionThere is a significant bidirectional association between NAFLD and depression. It is recommended to perform the screening for depression and enhance mental health monitoring in patients with NAFLD， and metabolic function assessment and exercise intervention should be performed for patients with depression.

Mitochondria are abundant in hepatocytes and play an important role in the normal operation of the liver. Mitochondrial division/fusion is two biological processes that maintain the dynamic balance of mitochondria， and it is closely associated with the change of cell function and the development and progression of diseases. Balance of mitochondrial division/fusion is of key significance in the treatment of many diseases. Recent studies have shown that abnormal mitochondrial division/fusion plays a significant role in fatty liver disease， hepatitis， liver fibrosis， and liver cancer， which are the four stages of the progression of liver diseases， and the therapeutic targets based on the regulation of such abnormalities are constantly being identified. By reviewing the role of mitochondrial division/fusion in different stages of liver disease， this article further demonstrates the role of mitochondrial division/fusion mechanism in chronic liver diseases and also provides a scientific basis for more ideas on the treatment， remission or even reversal of liver disease progression based on mitochondrial division/fusion.

Objective:To analyze the diagnostic value of bedside capsule endoscopy in patients with acute or severe gastrointestinal bleeding.Methods:Clinical data from patients who underwent bedside capsule endoscopy due to acute or severe suspected gastrointestinal bleeding in Nanfang Hospital, Southern Medical University from June 2018 to September 2021 were analyzed retrospectively. The efficacy of capsule endoscopy in detecting upper gastrointestinal tract and small intestinal bleeding was evaluated.Results:A total of 74 patients underwent bedside capsule endoscopy for suspected acute or severe gastrointestinal bleeding. Five patients were excluded due to failure of examination due to retention of capsule endoscope in the gastric lumen, and 69 were included in the study, of whom 54 patients with a definitive diagnosis of gastrointestinal hemorrhage. The positive detection rate of the capsule endoscopy was 83.33% (45/54), including 17 cases of ulcer, 5 cases of erosion, 5 cases of vascular malformation, 4 protrusion mass, 4 diverticulum, 5 obscure gastrointestinal bleeding, 1 stenosis , 1 active mucosal blood exudation, 1 gastric retention, 1 mucosal swelling, and 1 mucosal wrinkle change. The sensitivity and specificity of capsule endoscopy in the diagnosis of upper gastrointestinal bleeding were 92.31% (12/13) and 75.00% (3/4) respectively. The sensitivity and specificity of capsule endoscopy for diagnosing small intestinal bleeding were 80.49% (33/41) and 90.91% (10/11) respectively.Conclusion:Bedside capsule endoscopy demonstrates high sensitivity and specificity in the diagnosis of gastrointestinal bleeding, showing potential advantages in bedside applications for acute and severe gastrointestinal bleeding.

As a classical inflammatory response pathway,the nuclear factor-kappa B(NF-κB)signaling pathway plays a critical role in various physiological and pathological processes.Ferroptosis is a new form of non-apoptotic cell death,and recent studies have shown that there is a strong link between the NF-κB signaling pathway and ferroptosis,which affects the development and progression of liver diseases.Therefore,regulation of ferroptosis by targeting the NF-κB signaling pathway has a great potential in the treatment of liver diseases.This article discusses the influence of the NF-κB signaling pathway on the critical links such as lipid metabolism and iron metabolism during ferroptosis,as well as its mechanism of action in the positive and negative regulation of ferroptosis.Meanwhile,this article reviews the research advances in the role of this signaling pathway in liver diseases such as liver injury,nonalcoholic fatty liver disease,alcoholic liver disease,and hepatocellular carcinoma through the regulation of ferroptosis,so as to provide a reference for further understanding of the pathogenesis of liver diseases and the development of new therapeutic strategies.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

As a classical inflammatory response pathway,the nuclear factor-kappa B(NF-κB)signaling pathway plays a critical role in various physiological and pathological processes.Ferroptosis is a new form of non-apoptotic cell death,and recent studies have shown that there is a strong link between the NF-κB signaling pathway and ferroptosis,which affects the development and progression of liver diseases.Therefore,regulation of ferroptosis by targeting the NF-κB signaling pathway has a great potential in the treatment of liver diseases.This article discusses the influence of the NF-κB signaling pathway on the critical links such as lipid metabolism and iron metabolism during ferroptosis,as well as its mechanism of action in the positive and negative regulation of ferroptosis.Meanwhile,this article reviews the research advances in the role of this signaling pathway in liver diseases such as liver injury,nonalcoholic fatty liver disease,alcoholic liver disease,and hepatocellular carcinoma through the regulation of ferroptosis,so as to provide a reference for further understanding of the pathogenesis of liver diseases and the development of new therapeutic strategies.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To analyze the diagnostic value of bedside capsule endoscopy in patients with acute or severe gastrointestinal bleeding.Methods:Clinical data from patients who underwent bedside capsule endoscopy due to acute or severe suspected gastrointestinal bleeding in Nanfang Hospital, Southern Medical University from June 2018 to September 2021 were analyzed retrospectively. The efficacy of capsule endoscopy in detecting upper gastrointestinal tract and small intestinal bleeding was evaluated.Results:A total of 74 patients underwent bedside capsule endoscopy for suspected acute or severe gastrointestinal bleeding. Five patients were excluded due to failure of examination due to retention of capsule endoscope in the gastric lumen, and 69 were included in the study, of whom 54 patients with a definitive diagnosis of gastrointestinal hemorrhage. The positive detection rate of the capsule endoscopy was 83.33% (45/54), including 17 cases of ulcer, 5 cases of erosion, 5 cases of vascular malformation, 4 protrusion mass, 4 diverticulum, 5 obscure gastrointestinal bleeding, 1 stenosis , 1 active mucosal blood exudation, 1 gastric retention, 1 mucosal swelling, and 1 mucosal wrinkle change. The sensitivity and specificity of capsule endoscopy in the diagnosis of upper gastrointestinal bleeding were 92.31% (12/13) and 75.00% (3/4) respectively. The sensitivity and specificity of capsule endoscopy for diagnosing small intestinal bleeding were 80.49% (33/41) and 90.91% (10/11) respectively.Conclusion:Bedside capsule endoscopy demonstrates high sensitivity and specificity in the diagnosis of gastrointestinal bleeding, showing potential advantages in bedside applications for acute and severe gastrointestinal bleeding.