Reversal of tamoxifen resistance by artemisinin in ER+breast cancer:bioinformatics analysis and experimental validation

Breast cancer is the leading cause of cancer-related deaths in women worldwide,with Hormone Receptor(HR)+being the predominant subtype.Tamoxifen(TAM)serves as the primary treatment for HR+breast cancer.However,drug resistance often leads to recurrence,underscoring the need to develop new therapies to enhance patient quality of life and reduce recurrence rates.Artemisinin(ART)has demonstrated efficacy in inhibiting the growth of drug-resistant cells,positioning art as a viable option for counteracting endocrine resistance.This study explored the interaction between artemisinin and tamoxifen through a combined approach of bioinformatics analysis and experimental validation.Five characterized genes(ar,cdkn1a,erbb2,esr1,hsp90aa1)and seven drug-disease crossover genes(cyp2e1,rorc,mapk10,glp1r,egfr,pgr,mgll)were identified using WGCNA crossover analysis.Subsequent functional enrichment analyses were conducted.Our findings confirm a significant correlation between key cluster gene expression and immune cell infiltration in tamoxifen-resistant and-sensitized patients.scRNA-seq analysis revealed high expression of key cluster genes in epithelial cells,suggesting artemisinin’s specific impact on tumor cells in estrogen receptor(ER)-positive BC tissues.Molecular target docking and in vitro experiments with artemisinin on LCC9 cells demonstrated a reversal effect in reducing migratory and drug resistance of drug-resistant cells by modulating relevant drug resistance genes.These results indicate that artemisinin could potentially reverse tamoxifen resistance in ER-positive breast cancer.

Genetically Predicted Plasma Levels of Amino Acids and Endometriosis:A Mendelian Randomization Study

Endometriosis(EMS)is one of the most common disorders among women of reproductive age and affects approximately 6%–10%of the world total population^([1]).Women with EMS often experience symptoms such as dysmenorrhea,infertility,or difficulties in conceiving.Recent studies focusing on amino acids(AAs)metabolism have shed light on the mechanisms underlying the development and progression of EMS^([2]).

Effects of exercise training on glucose metabolism indicators and inflammatory markers in obese children and adolescents:A metaanalysis

BACKGROUND Obesity in children and adolescents is a serious problem,and the efficacy of exercise therapy for these patients is controversial.AIM To assess the efficacy of exercise training on overweight and obese children based on glucose metabolism indicators and inflammatory markers.METHODS The PubMed,Web of Science,and Embase databases were searched for randomized controlled trials related to exercise training and obese children until October 2023.The meta-analysis was conducted using RevMan 5.3 software to evaluate the efficacy of exercise therapy on glucose metabolism indicators and inflammatory markers in obese children.RESULTS In total,1010 patients from 28 studies were included.Exercise therapy reduced the levels of fasting blood glucose(FBG)[standardized mean difference(SMD):-0.78;95%confidence interval(CI):-1.24 to-0.32,P=0.0008],fasting insulin(FINS)(SMD:-1.55;95%CI:-2.12 to-0.98,P<0.00001),homeostatic model assessment for insulin resistance(HOMA-IR)(SMD:-1.58;95%CI:-2.20 to-0.97,P<0.00001),interleukin-6(IL-6)(SMD:-1.31;95%CI:-2.07 to-0.55,P=0.0007),C-reactive protein(CRP)(SMD:-0.64;95%CI:-1.21 to-0.08,P=0.03),and leptin(SMD:-3.43;95%CI:-5.82 to-1.05,P=0.005)in overweight and obese children.Exercise training increased adiponectin levels(SMD:1.24;95%CI:0.30 to 2.18,P=0.01)but did not improve tumor necrosis factor-alpha(TNF-α)levels(SMD:-0.80;95%CI:-1.77 to 0.18,P=0.11).CONCLUSION In summary,exercise therapy improves glucose metabolism by reducing levels of FBG,FINS,HOMA-IR,as well as improves inflammatory status by reducing levels of IL-6,CRP,leptin,and increasing levels of adiponectin in overweight and obese children.There was no statistically significant effect between exercise training and levels of TNF-α.Additional long-term trials should be conducted to explore this therapeutic perspective and confirm these results.

Efficacy and safety of perioperative therapy for locally resectable gastric cancer:A network meta-analysis of randomized clinical trials

BACKGROUND Gastric cancer(GC)is the fifth most commonly diagnosed malignancy worldwide,with over 1 million new cases per year,and the third leading cause of cancer-related death.AIM To determine the optimal perioperative treatment regimen for patients with locally resectable GC.METHODS A comprehensive literature search was conducted,focusing on phase II/III randomized controlled trials(RCTs)assessing perioperative chemotherapy and chemoradiotherapy in treating locally resectable GC.The R0 resection rate,overall survival(OS),disease-free survival(DFS),and incidence of grade 3 or higher nonsurgical severe adverse events(SAEs)associated with various perioperative regimens were analyzed.A Bayesian network meta-analysis was performed to compare treatment regimens and rank their efficacy.RESULTS Thirty RCTs involving 8346 patients were included in this study.Neoadjuvant XELOX plus neoadjuvant radiotherapy and neoadjuvant CF were found to significantly improve the R0 resection rate compared with surgery alone,and the former had the highest probability of being the most effective option in this context.Neoadjuvant plus adjuvant FLOT was associated with the highest probability of being the best regimen for improving OS.Owing to limited data,no definitive ranking could be determined for DFS.Considering nonsurgical SAEs,FLO has emerged as the safest treatment regimen.CONCLUSION This study provides valuable insights for clinicians when selecting perioperative treatment regimens for patients with locally resectable GC.Further studies are required to validate these findings.

Exploring the autophagy-related pathogenesis of active ulcerative colitis

BACKGROUND The pathogenesis of ulcerative colitis(UC)is complex,and recent therapeutic advances remain unable to fully alleviate the condition.AIM To inform the development of novel UC treatments,bioinformatics was used to explore the autophagy-related pathogenesis associated with the active phase of UC.METHODS The GEO database was searched for UC-related datasets that included healthy controls who met the screening criteria.Differential analysis was conducted to obtain differentially expressed genes(DEGs).Au-tophagy-related targets were collected and intersected with the DEGs to identiy differentially expressed autophagy-related genes(DEARGs)associated with active UC.DEARGs were then subjected to KEGG,GO,and DisGeNET disease enrichment analyses using R software.Differential analysis of immune infiltrating cells was performed using the CiberSort algorithm.The least absolute shrinkage and selection operator algorithm and protein-protein interaction network were used to narrow down the DEARGs,and the top five targets in the Dgree ranking were designated as core targets.RESULTS A total of 4822 DEGs were obtained,of which 58 were classified as DEARGs.SERPINA1,BAG3,HSPA5,CASP1,and CX3CL1 were identified as core targets.GO enrichment analysis revealed that DEARGs were primarily enriched in processes related to autophagy regulation and macroautophagy.KEGG enrichment analysis showed that DEARGs were predominantly associated with NOD-like receptor signaling and other signaling pathways.Disease enrichment analysis indicated that DEARGs were significantly linked to diseases such as malignant glioma and middle cerebral artery occlusion.Immune infiltration analysis demonstrated a higher presence of immune cells like activated memory CD4 T cells and follicular helper T cells in active UC patients than in healthy controls.CONCLUSION Autophagy is closely related to the active phase of UC and the potential targets obtained from the analysis in this study may provide new insight into the treatment of active UC patients.

Evaluation of the Effect and Efficiency of Ear Tip Bloodletting Combined with Xianfang Huoming Yin in the Treatment of Early-Stage Wheals

Objective:To evaluate the effect and efficiency of ear tip bloodletting combined with Xianfang Huoming Yin(XFH)in the treatment of early-stage wheals.Methods:70 patients with early-stage wheals admitted from September 2020 to September 2022 were divided into two groups by randomized numerical table method,with 35 cases/group.Both groups received conventional treatment,the control group combined with XFH,and the observation group combined with ear tip bloodletting therapy and XFH.Conscious symptom scores,ocular indexes,therapeutic effects,and sleep quality between the two groups were compared.Results:After the treatment,the patients in the observation group had lower self-awareness symptom scores and sleep quality scores as compared to those in the control group;the diameter of the mass in the observation group was smaller than that of the control group after treatment;the average tear film rupture time and the time taken for the first non-contact tear film to rupture were longer in the observation group than those in the control group;the total effective rate of the treatment in the observation group was higher than that of the control group(P<0.05).Conclusion:Ear tip bloodletting combined with XFH was ideal for the treatment of early-stage wheals and has a high effective rate.

Mechanism of Huatan Sanjie Fang in improving goiter in Graves'disease mice based on the Hippo signaling pathway

Objective:To explore the mechanism of Huatan Sanjie Fang(HTSJ)in regulating goiter in Graves'disease(GD)mice by detecting key factors of the Hippo signaling pathway.Methods:A mouse model of GD was established by injecting Ad-TSHR289 adenovirus into the bilateral quadriceps femoris of female mice.Successful mouse models were then randomly divided into a model group,methimazole(MMI)group,and HTSJ group,and fed with deionized water,MMI(4.5 mg/kg per day),and HTSJ(35.10 g/kg per day),respectively,for 10 weeks.Histopathological changes of the thyroid gland were subsequently observed by hematoxylin-eosin staining.Radioimmunoassay was used to detect serum total thyroxine(T4)and thyrotrophin-receptor antibody(TRAb)levels.The relative expression of mRNA of Mst1,YAP,and TAZ were detected by quantitative real-time polymerase chain reaction,while the protein expression of Mst1,YAP,TAZ,pMst1,and pYAP were detected by western blot.Results:After 10 weeks of drug intervention,goiter and other pathological changes in the HTSJ group significantly improved compared with the model group,and the levels of serum T4 and TRAb significantly decreased(P=.002,P<.001,respectively).Decreased mRNA expression of Mst1,YAP,and TAZ,the key factors of the Hippo signaling transduction pathway,was also observed(P=.002,P=.022,P<.001,respectively).In contrast,protein expression of Mst1(P=.046),pMst1(P=.026),and p YAP(P=.004)increased,while protein expression of YAP and TAZ decreased(P=.041,P<.001,respectively).Conclusion:HTSJ can effectively improve goiter in GD mice through the Hippo signaling pathway.

Metastatic colon cancer treated using traditional Chinese medicine combined with chemotherapy:A case report

BACKGROUND Colon cancer(CC)is one of the leading causes of cancer-related morbidity and mortality worldwide.Traditional Chinese medicine(TCM)is widely used in the treatment of various chronic diseases.CC easily metastasizes and results in high morbidity and mortality rates.CASE SUMMARY A 71-year-old man with a 12-year history of old myocardial infarction and a 7-year history of type 2 diabetes mellitus was diagnosed with CC and underwent right hemicolectomy 1 year ago.Tumor biopsy revealed moderately poorly differentiated adenocarcinoma.Subsequently,chemotherapy with oxaliplatin and paclitaxel was administered.Anastomosis recurrence and pelvic metastasis were noted 37 d later.The patient received eight 21-d cycles of adjuvant chemotherapy with oxaliplatin and capecitabine after recurrence.However,the tumor persisted,and chemotherapy-related liver damage developed gradually.Thus,he was advised to take TCM for the recurrence and pelvic metastasis.The patient’s metastatic CC was cured after receiving TCM combined with long-term chemotherapy.CONCLUSION TCM may be an effective adjunct therapy in the treatment of patients with metastatic CC.

Large animal models of cardiac ischemia-reperfusion injury:Where are we now?

Large animal models of cardiac ischemia-reperfusion are critical for evaluation of the efficacy of cardioprotective interventions prior to clinical translation.Nonetheless,current cardioprotective strategies/interventions formulated in preclinical cardiovascular research are often limited to small animal models,which are not transferable or reproducible in large animal models due to different factors such as:(i)complex and varied features of human ischemic cardiac disease(ICD),which are challenging to mimic in animal models,(ii)significant differences in surgical techniques applied,and(iii)differences in cardiovascular anatomy and physiology between small versus large animals.This article highlights the advantages and disadvantages of different large animal models of preclinical cardiac ischemic reperfusion injury(IRI),as well as the different methods used to induce and assess IRI,and the obstacles faced in using large animals for translational research in the settings of cardiac IR.

Guideline for the diagnosis and treatment of rheumatoid arthritis with integrated traditional Chinese medicine and Western medicine to increase efficiency and reduce toxicity

Rheumatoid arthritis imposes a huge disease burden.Existing practice guidelines do not meet the needs of integrated traditional Chinese medicine and Western medicine in the treatment of rheumatoid arthritis.We established a guideline working group consists of a steering committee,a secretary group,an evidence evaluation group,a consensus group and a review group and developed a guideline following the guidance of the World Health Organization Handbook and the Chinese Medical Association.The guideline includes 35 recommendations which reached consensus by the two rounds Delphi surveys.These recommendations were formulated to address the following themes of most concern to clinician:diagnostic imaging,disease staging,traditional Chinese medicine syndromes,effectiveness and toxicity of integrated traditional Chinese medicine and Western medicine.

Combination of symptoms, syndrome and disease: Treatment of refractory diabetic gastroparesis

AIM:To assess effect of combination of symptoms,syndrome and disease on treatment of diabetic gastroparesis with severe nausea and vomiting.METHODS:Professor Tong Xiaolin’s clinical electronic medical records of patients who were treated between January 1,2006 and October 1,2012 were used as a database.Patients who met the inclusion criteria were enrolled.General information(name,sex and age),symptoms and blood glucose levels were obtained from the clinic electronic medical record,which was supplemented by a telephone interview.The patient-rated Gastroparesis Cardinal Symptom Index(GCSI)was used to evaluate the severity of the symptoms of gastroparesis.The effects of the treatment were assessed by the change in the severity of the symptoms of gastroparesis and the change in blood glucose between the baseline levels and the post-treatment levels at 1,2,4,8 and 12 wk.RESULTS:Forty-five patients had a mean GCSI nausea and vomiting severity score of 4.21±0.67 and a total GCSI score of 2.77±0.63 before treatment.There was a significant improvement in the nausea and vomiting score at every return visit compared with the baseline score(1 wk:3.02±1.04 vs 4.18±0.71,P<0.001;2wk:2.32±1.25 vs 4.16±0.73,P<0.001;4 wk:2.12±1.26 vs 4.12±0.73,P<0.001;8 wk:1.79±1.09vs 4.24±0.77,P<0.001;12 wk:0.69±0.92 vs 4.25±0.70,P<0.001).Twenty-five of the 45 patients had complete resolution of vomiting during the observation period(mean time to resolution was 37.9±27.3 d).The postprandial fullness and early satiety subscale,bloating subscale and total GCSI scores were also improved.Finally,the blood glucose levels improved after treatment,although the change was not significant.CONCLUSION:Use of the combination of symptoms,syndrome and disease to treat diabetic gastroparesis with refractory nausea and vomiting may be a new treatment option.

Pathological process of liver sinusoidal endothelial cells in liver diseases

Cirrhosis develops from liver fibrosis and is the severe pathological stage of all chronic liver injury. Cirrhosis caused by hepatitis B virus and hepatitis C virus infection is especially common. Liver fibrosis and cirrhosis involve excess production of extracellular matrix,which is closely related to liver sinusoidal endothelial cells(LSECs). Damaged LSECs can synthesize transforming growth factor-beta and platelet-derived growth factor,which activate hepatic stellate cells and facilitate the synthesis of extracellular matrix. Herein,we highlight the angiogenic cytokines of LSECs related to liver fibrosis and cirrhosis at different stages and focus on the formation and development of liver fibrosis and cirrhosis. Inhibition of LSEC angiogenesis and antiangiogenic therapy are described in detail. Targeting LSECs has high therapeutic potential for liver diseases. Further understanding of the mechanism of action will provide stronger evidence for the development of anti-LSEC drugs and new directions for diagnosis and treatment of liver diseases.

Treatment of refractory diabetic gastroparesis: Western medicine and traditional Chinese medicine therapies

Refractory diabetic gastroparesis(DGP),a disorder that occurs in both type 1 and type 2 diabetics,is associated with severe symptoms,such as nausea and vomiting,and results in an economic burden on the health care system.In this article,the basic characteristics of refractory DGP are reviewed,followed by a discussion of therapeutic modalities,which encompasses the definitions and clinical manifestations,pathogenesis,diagnosis,and therapeutic efficacy evaluation of refractory DGP.The diagnostic standards assumed in this study are those set forth in the published literature due to the absence of recognized diagnosis criteria that have been assessed by an international organization.The therapeutic modalities for refractory DGP are as follows:drug therapy,nutritional support,gastricelectrical stimulation,pyloric botulinum toxin injection,endoscopic or surgical therapy,and traditional Chinese treatment.The therapeutic modalities may be used alone or in combination.The use of traditional Chinese treatments is prevalent in China.The effectiveness of these therapies appears to be supported by preliminary evidence and clinical experience,although the mechanisms that underlie these effects will require further research.The purpose of this article is to explore the potential of combined Western and traditional Chinese medicine treatment methods for improved patient outcomes in refractory DGP.

Mechanism underlying the protective effect of Kaixin Jieyu Fang on vascular depression following cerebral white matter damage

The Chinese compound Kaixin fieyu Fang can be used to treat vascular depression; however, the underlying mechanism remains unclear. This study established a rat model of chronic cerebral ischemia-caused white matter damage by ligation of the bilateral common carotid arteries. Rats received daily intragastric administration of a suspension of Kaixin ]ieyu Fang powder. After 3, 7 and 21 days of treatment, the degree of white matter damage in the cerebral ischemia rat model was alleviated, Bcl-2 protein and mRNA expression in brain tissue increased, and Bax protein and mRNA expression decreased. These results indicate that Kaixin Jieyu Fang can alleviate cere- bral white matter damage, and the underlying mechanism is associated with regulation of Bcl-2/ Bax protein and mRNA expression, which is one of possible mechanism behind the protective effect of Kaixin Jieyu Fang against vascular depression.

The Effect of Sleep Deprivation on Coronary Heart Disease

Sleep deprivation(SD) has been associated with an increased morbidity and mortality of coronary heart disease(CHD). SD could induce autonomic nervous dysfunction, hypertension, arrhythmia, hormonal dysregulation, oxidative stress, endothelial dysfunction, inflammation and metabolic disorder in CHD patients. This paper reviewed the study results of SD in clinical trials and animal experiments and concluded that SD was associated with cardiovascular risk factors, which aggravated CHD in pathogenesis and outcomes.

General Survey of Traditional Chinese Medicine and Western Medicine Researches on Tumor Metastasis

Metastasis and recurrence of tumors is the chief cause of death for such patients. Therefore, researches on the mechanism of its metastasis, prevention and treatment are the focal points in the field of traditional Chinese medicine （TCM） and Western medicine （WM） at present. WM practitioners＂ study on tumor metastasis involved its occurrence and development including every detail and process, and now it even has developed into the molecular biological field. py is used as the main means, but the efficacy is not n treatment surgical operation and radio- chemotheratoo optimistic. In recent years, TOM, as part of the comprehensive therapy, has been gradually gaining attention of oncologists. Aimed at solving the difficult problems in metastasis of tumor, many TOM practitioners on the basis of syndrome differentiation have raised theories about the cause of tumor metastasis. On the basis of these theories, some TOM recipes against tumor metastasis have been developed to serve as an effective supplement to surgical operation, radio- and chemotherapy. The present article summarizes research results in recent years about the cause of formation of tumor and its metastasis by TOM and WM, so as to offer some theoretical clues to the study of tumors metastasis.

Construction of an Artificial Intelligence Traditional Chinese Medicine Diagnosis and Treatment Model Based on Syndrome Elements and Small-Sample Data

1.Introduction The combination of traditional Chinese medicine(TCM)and Western medicine has advantages in the treatment of chronic and complex diseases,for example,the introduction and application of TCM during the coronavirus disease 2019(COVID-19)epidemic in Hubei Province,China,had a total effective rate of 90%,thus establishing the efficacy of integrating TCM and Western medicine.However,the integration of TCM diagnosis and treatment methods with modern medicine,as well as their further development,is limited due to several significant challenges.

The effects and prospects of the integration of traditional Chinese medicine and Western medicine on andrology in China

Andrology has a long history in traditional Chinese medicine （TCM） discussions concerning andropathies, and documentation of relevant therapeutic methods abound in the ancient literature on TCM. Integrated treatment combining TCM and Western medicine has seen both broad and in-depth development, with formidable status in the field of modern andrology in China. This article attempts to demonstrate the unique advantage of integrated treatment in the therapy of andropathies through a review of the ancient literature on andrology in the field of TCM and on the integrative treatment of prostatic diseases, sexual dysfunction, male infertility and late-onset hypogonadism. There is a need for the advancement of a medical theory that integrates TCM and Western medicine practices to create a new therapeutic system with standardized therapeutic and evaluative protocols for diseases involving male sexual health.

Effects of Ge Gen Decoction on PGE2 Content and COX Activity in the Degenarated Cervical Intervertebral Discs of Rats

After the rat model of cervical spondylosis was developed for 6 months, the PGE2 content and COX activity in the cervical intervertebral discs were determined respectively by radioimmunoassay and catalytic activity assay.The results indicated that the PGF2 content and COX activity in the model rat increased significantly, and that Ge Gen Decoction could down-regulate the PGE2 content and inhibit COX activity. This is possibly one of the mechanisms of Ge Gen Decoction for treating cervical spondylosis.