OBJECTIVE: To investigate the effect of acupuncture on advanced cancer patients by meta-analysis. METHODS: Nine databases (the Cochrane Central Register of Controlled Trials, MEDLINE, Web of Science, Embase, China National Knowledge Infrastructure, the Cumulative Index to Nursing and Allied Health Literature, Chinese Biomedical Literature Database, China Science and Technology Journal Database, and WanFang Data) were searched for randomized controlled trials (RCTs) on acupuncture in advanced cancer patients published from inception to February 13, 2023 and updated to June 1, 2023. Primary outcomes were quality of life (QOL), while secondary outcomes were pain, fatigue, and adverse events (side effects). Data synthesis was performed using RevMan V.5.3 to calculate pooled effect sizes. RoB-2 was used for the risk of bias, and the quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. RESULTS: Totally 17 RCTs involving 1,178 participants were included, 15 of which were pooled for meta-analysis. Most studies demonstrated some concern for the overall risk of bias. The pooled data indicated that acupuncture was associated with improved QOL [mean difference (MD)=6.67, 95% confidence interval (CI): 5.09 to 8.26], pain (MD=-1.18, 95% CI -2.28 to -0.08), and adverse events (risk ratio=0.30, 95% CI: 0.26 to 0.57) compared with control groups. Fatigue outcome was not included. Heterogeneity was substantial, and GRADE evidence was very low for both QOL and pain. CONCLUSIONS Acupuncture could benefit patients with advanced cancer and is considered safe compared with usual care. However, the evidence regarding QOL and pain outcomes requires further validation. It is crucial to encourage the development of high-quality studies to strengthen this evidence. (Registry No. CRD42023423539).
Humans ; Acupuncture Therapy ; Neoplasms/therapy* ; Quality of Life ; Randomized Controlled Trials as Topic ; Treatment Outcome

Delirium is a common cause and complication of hospitalization in the elderly and is associated with higher risk of future dementia and progression of existing dementia, of which 70% is Alzheimer's disease (AD). AD and delirium, which are known to be aggravated by one another, represent significant societal challenges, especially in light of the absence of effective treatments. The intricate biological mechanisms have led to numerous clinical trial setbacks and likely contribute to the limited efficacy of existing therapeutics. Artificial intelligence (AI) presents a promising avenue for overcoming these hurdles by deploying algorithms to uncover hidden patterns across diverse data types. This review explores the pivotal role of AI in revolutionizing drug discovery for AD and delirium from target identification to the development of small molecule and protein-based therapies. Recent advances in deep learning, particularly in accurate protein structure prediction, are facilitating novel approaches to drug design and expediting the discovery pipeline for biological and small molecule therapeutics. This review concludes with an appraisal of current achievements and limitations, and touches on prospects for the use of AI in advancing drug discovery in AD and delirium, emphasizing its transformative potential in addressing these two and possibly other neurodegenerative conditions.

Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case-control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk. Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis. Results After Bonferroni correction,the case-control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population. Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.

Humans ; Osteoblastoma/surgery* ; Neck/surgery* ; Spinal Neoplasms ; Cervical Vertebrae

Objective To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/-mice.Methods The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/-mice.Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers.Results Proteomic analysis showed that there were 43 significantly up-regulated and 58 sig-nificantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group.Among them,GBP2,TAOK3,TFR1 and UCP1 were biomarkers with great diagnostic potential.KEGG pathway enrichment analysis indicated that fer-roptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model.The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model.Conclusion Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferrop-tosis.Four potential biomarkers are selected for myocardial injury diagnosis,providing a new direction for sudden cardiac death(SCD)caused by hyperlipidemia combined with the restraint stress.

AIM To explore the clinical effects of Zhenwu Decoction combined with Danshen Drink on patients with chronic heart failure.METHODS Eighty-six patients were randomly assigned into control group(43 cases)for 4-week intervention of conventional treatment,and observation group(43 cases)for 4-week intervention of Zhenwu Decoction,Danshen Drink and conventional treatment.The changes in cardiac function indices(LVFS,LVEDD,LVEF),serum indices(hs-cTnI,sST2,NT-proBNP,MMP-9),inflammatory factors(IL-6,TNF-α,hs-CRP),platelet aggregation rate,QTcd and incidence of adverse reactions were detected.RESULTS After the treatment,the two groups demonstrated increased LVFS,LVEF(P＜0.05),and decreased LVEDD,serum indices,inflammatory factors,platelet aggregation rate,QTcd(P＜0.05),especially for the observation 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 chronic heart failure,Zhenwu Decoction combined with Danshen Drink can safely and effectively improve hs-cTnI level and platelet aggregation functions.

Objective To investigate the control status of bronchial asthma(referred to as"asthma")in school-age children with normal pulmonary ventilation function and the occurrence of acute attacks within 1 year of follow-up.Methods A retrospective analysis was conducted on clinical data of 327 children aged 6-14 years with bronchial asthma and normal pulmonary ventilation function from April to September 2021.Based on the measured value of one second rate(FEV1/FVC),the children were divided into the ≥80％group(267 cases)and the＜80％group(60 cases).The pulmonary ventilation function,asthma control level,and occurrence of acute attacks within 1 year were compared between the two groups.Results The baseline pulmonary ventilation function in the＜80％group was lower than that in the ≥80％group,and the proportion of small airway dysfunction was higher than that in the ≥80％group(P＜0.05).After standardized treatment for 1 year,the small airway function indices in the＜80％group improved but remained lower than those in the ≥80％group(P＜0.05).The rate of incomplete asthma control at baseline was 34.6％(113/327),and the asthma control level in the＜80％group was lower than that in the ≥80％group(P＜0.05).After standardized treatment for 1 year,the asthma control level in the＜80％group remained lower than that in the ≥80％group,and the proportion of acute asthma attacks was higher than that in the ≥80％group(P＜0.05).Conclusions Approximately one-third of school-age children with asthma still have incomplete asthma control when their pulmonary ventilation function is normal.Among them,children with measured FEV1/FVC＜80％have an increased risk of acute asthma attacks and require close follow-up and strengthened asthma management.

OBJECTIVE: Despite the combination of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang (SB-SD) being a recognized Chinese medicinal herbal pair that is commonly used in the treatment of ovarian cancer, there is a poor understanding of their pharmacological mechanisms. This study examines the antitumor properties and potential mechanisms of SB-SD on human ovarian cancer A2780 cells through a multi-omics approach, establishing a pharmacological basis for clinical utilization. METHODS: A range of mass ratios and reagents were used in the hot reflux extraction of SB-SD. The inhibitory effect of the SB-SD extracts on A2780 cell proliferation was assessed using the cell-counting kit 8 assay. A zebrafish tumor implantation model was used to evaluate the effects of SB-SD extracts on tumor growth and metastasis in vivo. Transcriptomics and proteomics were used to investigate alterations in biological pathways in A2780 cells after treatment with different concentrations of SB-SD extract. Cell cycle, cell apoptosis, intracellular free iron concentration, intracellular reactive oxygen species (ROS) concentration, malondialdehyde (MDA), and mitochondrial membrane potential were measured. Real-time quantitative reverse transcription polymerase chain reaction and Western blotting were utilized to investigate the effects of heme catabolism and ferritinophagy on ferroptosis induced by SB-SD extract in A2780 cells. RESULTS: The 70% ethanol extract of SB-SD (a mass ratio of 4:1) inhibited A2780 cell proliferation significantly with a half maximal inhibitory concentration of 660 μg/mL in a concentration- and time-dependent manner. Moreover, it effectively suppressed tumor growth and metastasis in a zebrafish tumor implantation model. SB-SD extract induced the accumulation of free iron, ROS, MDA, and mitochondrial damage in A2780 cells. The mechanisms might involve the upregulated expression of ferritinophagy-related genes microtubule-associated protein 1 light chain 3, autophagy-related gene 5, and nuclear receptor coactivator 4. CONCLUSION SB-SD extract effectively inhibited the development of ovarian cancer both in vitro and in vivo. Its mechanism of action involved inducing ferroptosis by facilitating heme catabolism and ferritinophagy. This herbal pair holds promise as a potential therapeutic option for ovarian cancer treatment and may be utilized in combination with routine treatment to improve the treatment outcomes of ovarian cancer patients. Please cite this article as: Wang Z, Liu M, Li GX, Zhang L, Ding KY, Li SQ, Gao BQ, Chen P, Choe HC, Xia LY, Yang YT, Liu Y, Sui X, Ma JN, Zhang L. A herbal pair of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang induced ferroptosis in ovarian cancer A2780 cells via inducing heme catabolism and ferritinophagy. J Integr Med. 2024; 22(6): 666-683.
Ferroptosis/drug effects* ; Female ; Humans ; Animals ; Scutellaria/chemistry* ; Ovarian Neoplasms/genetics* ; Zebrafish ; Cell Line, Tumor ; Ferritins/genetics* ; Plant Extracts/pharmacology* ; Heme/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Cell Proliferation/drug effects* ; Reactive Oxygen Species/metabolism* ; Antineoplastic Agents, Phytogenic/pharmacology* ; Autophagy/drug effects* ; Apoptosis/drug effects*

Objective To explore the acute effects of NO₂ on children's respiratory hospitalization risk in Foshan City. Methods The daily average concentrations of six air pollutants such as NO2 and fine particulate matter, and meteorological data including average temperature and relative humidity in Foshan were collected from 2016 to 2019. Data on the daily number of children newly hospitalized for respiratory diseases (ECRH) in Foshan Women and Children Hospital were retrieved. Time series analysis was used to quantitatively evaluate the effect of daily NO2 concentration on the hospitalization risk of children with respiratory diseases. Results From 2016 to 2019, the average ECRH in the hospital was 10. The daily average concentrations of air pollutants NO₂, PM_2.5, PM₁₀, and SO₂ were 42.0 μg/m³, 35.3 μg/m³, 58.1 μg/m³, and 11.4 μg/m³, respectively. The air pressure, daily average temperature and relative humidity of atmosphere were 1008.4 Pa, 23.7℃ and 73.3%, respectively. ECRH was significantly correlated with the daily average concentration of NO2 (r=0.079, P<0.05). After excluding temperature, humidity and other influencing factors, for every 10 μg/m³ increase of NO2 concentration in the single pollutant model, the excess risk of ECHR in the hospital increased by 1.22% (95% CI: 0.06%, 2.40%) and 1.37% (95% CI: 0.23%, 2.53%) in lag0 and Lag1 day, respectively. The strongest effect appeared in lag0:7 with the excess risk increasing by 1.70% (95% CI:0.12%, 3.31%). In the NO₂ + SO₂ + CO + O₃_8h + PM_2.5 and NO₂ + SO₂ + CO + O₃_8h + PM₁₀ multi-pollutant models, significance correlation still existed between the daily average NO₂ concentration and ECHR in lag0, lag1 and lag0:1 to lag0:7. The strongest effect appeared in lag0:1, and the excess risks were 4.06% (95% CI: 1.83%, 6.34%) and 3.95% (95% CI: 1.85%, 6.09%), respectively. Dose-response relationship analysis showed a linear relationship between the daily average NO₂ concentration and ECHR, and the excess risk of new hospitalization gradually increased with the increase of daily average NO₂ concentration. Conclusion There was a significant correlation between NO₂ concentration and hospitalization risk of children with respiratory diseases in Foshan City, which suggests that the government should further strengthen the prevention and control of air pollution.

A randomized, double-blind, placebo-controlled, multi-center phase Ⅱ clinical trial design was used in this study to recruit subjects who were in line with the syndrome of excess heat and fire toxin, and were diagnosed as recurrent oral ulcers, gingivitis, and acute pharyngitis. A total of 240 cases were included and randomly divided into a placebo group and a Huanglian Jiedu Pills group. The clinical efficacy of Huanglian Jiedu Pills in treating the syndrome of excess heat and fire toxin was evaluated by using the traditional Chinese medicine(TCM) syndrome scale. Enzyme-linked immunosorbent assay(ELISA) was used to determine and evaluate the levels of adenosine triphosphate(ATP), 4-hydroxynonenal(4-HNE), and adrenocorticotropic hormone(ACTH) in plasma of the two groups before and after administration and to predict their application value as clinical biomarkers. The results showed that the disappearance rate of main symptoms in the Huanglian Jiedu Pills group was 69.17%, and that in the placebo group was 50.83%. The comparison between the Huanglian Jiedu Pills group and the placebo group showed that 4-HNE before and after administration was statistically significant(P<0.05). The content of 4-HNE in the Huanglian Jiedu Pills group decreased significantly after administration(P<0.05), but that in the placebo group had no statistical significance and showed an upward trend. After administration, the content of ATP in both Huanglian Jiedu Pills group and placebo group decreased significantly(P<0.05), indicating that the energy metabolism disorder was significantly improved after administration of Huanglian Jiedu Pills and the body's self-healing ability also alleviated the increase in ATP level caused by the syndrome of excess heat and fire toxin to a certain extent. ACTH in both Huanglian Jiedu Pills group and placebo group decreased significantly after administration(P<0.05). It is concluded that Huanglian Jiedu Pills has a significant clinical effect, and can significantly improve the abnormal levels of ATP and 4-HNE in plasma caused by the syndrome of excess heat and fire toxin, which are speculated to be the effective clinical biomarkers for Huanglian Jiedu Pills to treat the syndrome of excess heat and fire toxin.
Humans ; Adrenocorticotropic Hormone ; Hot Temperature ; Medicine, Chinese Traditional ; Adenosine Triphosphate