Iron and ferritin effects on intensive care unit mortality:A metaanalysis

BACKGROUND The effect of serum iron or ferritin parameters on mortality among critically ill patients is not well characterized.AIM To determine the association between serum iron or ferritin parameters and mortality among critically ill patients.METHODS Web of Science,Embase,PubMed,and Cochrane Library databases were searched for studies on serum iron or ferritin parameters and mortality among critically ill patients.Two reviewers independently assessed,selected,and abstracted data from studies reporting on serum iron or ferritin parameters and mortality among critically ill patients.Data on serum iron or ferritin levels,mortality,and demographics were extracted.RESULTS Nineteen studies comprising 125490 patients were eligible for inclusion.We observed a slight negative effect of serum ferritin on mortality in the United States population[relative risk(RR)1.002;95%CI:1.002-1.004].In patients with sepsis,serum iron had a significant negative effect on mortality(RR=1.567;95%CI:1.208-1.925).CONCLUSION This systematic review presents evidence of a negative correlation between serum iron levels and mortality among patients with sepsis.Furthermore,it reveals a minor yet adverse impact of serum ferritin on mortality among the United States population.

Protective effects of quercetin against H2O2 induced KGN cells injury

Background:Oxidative stress is one of the key contributors to cellular senescence and ovarian aging.Quercetin has a variety of physiological activities such as antioxidant.Given that hydrogen peroxide can cause oxidative damage to cells,the present study is designed to verify the protective effect of quercetin on human ovarian granulosa tumor cell line under oxidative stress.Methods:Cell counting kit-8 and lactate dehydrogenase assays examined cell viability and toxicity.Flow cytometry detected reactive oxygen species accumulation.Glutathione level was measured to analyze the oxidation resistance.Cell apoptosis was evaluated by Hoechst 33258 staining,acridine orange/Ethidium Bromide staining and western blot.The mitochondrial structure was observed under a transmission electron microscope.Mitochondrial membrane integrity was detected by JC-1 staining and western blot.Results:Hydrogen peroxide could induce cell injury,promote reactive oxygen species accumulation,and lead to glutathione depletion.hydrogen peroxide also resulted in mitochondrial morphological damage and depolarization,which activate caspase3/9 subsequently.However,quercetin could mitigate these damages.Conclusions:Present study found that hydrogen peroxide induced oxidative stress and mitochondrial apoptosis of human ovarian granulosa tumor cell line cells,which could be attenuated by quercetin.

Left bundle branch area pacing combined with implantable cardioverter-defibrillator treatment for heart failure after myocardial infarction

Left bundle branch area pacing(LBBAP)has emerged as a new physiological pacing mode.Previous studies have confirmed the feasibility and efficacy of LBBAP for cardiac resynchronization therapy(CRT)in heart failure(HF)patients with left bundle branch block(LBBB)and a narrower QRS duration(QRSd)to have a higher percentage of super responders,and lower pacing thresholds than biventricular pacing(BiVP).

Can Tibetan medicine Honghua Ruyi pills relieve endometriosisassociated dysmenorrhea?Protocol for a randomized placebocontrolled trial

Objective:To provide high-quality clinical evidence of the efficacy of Tibetan medicine Honghua Ruyi(HHRY)pills for endometriosis-associated dysmenorrhea.Methods:This study constitutes a multicenter,randomized,double-blind,placebo-controlled trial encompassing a three-menstrual cycle intervention followed by a three-menstrual cycle follow-up period.A total of 164 eligible females with endometriosis-associated dysmenorrhea were randomly divided into HHRY pills and placebo groups in a 1:1 ratio.The primary outcome included dysmenorrhea symptoms assessed using Visual Analog Scale(VAS)scores and quality of life,whereas the secondary outcome measures included the maximum VAS for non-menstrual pelvic pain,duration of pain episodes(in days),frequency and quantity of the consumption of ibuprofen sustained-release capsules(or other non-steroidal anti-inflammatory drugs),and days off work/study for staff/student due to dysmenorrhea,ovarian cyst,and/or pelvic nodule size.The safety was monitored throughout the treatment period.All the analyses were based on the intention-to-treat principle.For continuous outcomes,simple or multiple linear regressions were used to estimate the differences between the HHRY pills and placebo groups,with categorical data expressed as the number and percentage of occurrences.Differences were compared using the chi-square test or Fisher's exact test.The predefined analysis was adjusted for concomitant treatment,a variable considered to be associated with outcomes but unaffected by treatment allocation.Estimates of treatment effects were reported with 95%confidence intervals.Two-tailed P values≤.05 were considered statistically significant.Conclusion:Positive results from this trial,upon completion would provide robust evidence for the efficacy and safety of HHRY pills in treating dysmenorrhea in patients with endometriosis.

Analysis of the causes of primary revision after unicompartmental knee arthroplasty: A case series

BACKGROUND Unicompartmental knee arthroplasty(UKA)has great advantages in the treatment of unicompartmental knee osteoarthritis,but its revision rate is higher than that of total knee arthroplasty.AIM To summarize and analyse the causes of revision after UKA.METHODS This is a retrospective case series study in which the reasons for the first revision after UKA are summarized.We analysed the clinical symptoms,medical histories,laboratory test results,imaging examination results and treatment processes of the patients who underwent revision and summarized the reasons for primary revision after UKA.RESULTS A total of 13 patients,including 3 males and 10 females,underwent revision surgery after UKA.The average age of the included patients was 67.62 years.The prosthesis was used for 3 d to 72 months.The main reasons for revision after UKA were improper suturing of the surgical opening(1 patient),osteophytes(2 patients),intra-articular loose bodies(2 patients),tibial prosthesis loosening(2 patients),rheumatoid arthritis(1 patient),gasket dislocation(3 patients),anterior cruciate ligament injury(1 patient),and medial collateral ligament injury with residual bone cement(1 patient).CONCLUSION The causes of primary revision after UKA were gasket dislocation,osteophytes,intra-articular loose bodies and tibial prosthesis loosening.Avoidance of these factors may greatly reduce the rate of revision after UKA,improve patient satisfaction and reduce medical burden.

Research on the development methodology for clinical practice guidelines for organic integration of traditional Chinese medicine and Western medicine

Integrated traditional Chinese medicine(TCM)and Western medicine(WM)is a new medical science grounded in the knowledge bases of both TCM and WM,which then forms a unique modern medical system in China.Integrated TCM and WM has a long history in China,and has made important achievements in the process of clinical diagnosis and treatment.However,the methodological defects in currently published clinical practice guidelines(CPGs)limit its development.The organic integration of TCM and WM is a deeper integration of TCM and WM.To realize the progression of"integration"to"organic integration",a targeted and standardized guideline development methodology is needed.Therefore,the purpose of this study is to establish a standardized development procedure for clinical practice guidelines for the organic integration of TCM and WM to promote the systematic integration of TCM and WM research results into clinical practice guidelines in order to achieve optimal results as the whole is greater than the sum of the parts.

Prediction of prognosis,immune escape and drug sensitivity of lung adenocarcinoma based on Cuproptosis-related LncRNA

Background:Lung Adenocarcinoma(LUAD)is the leading cause of death from lung cancer.Cuproptosis is the latest discovered way of programmed cell death,and Cuproptosis-Related Gene(CRG)is associated with the risk of LUAD.At present,there are few research of LUAD and Cuproptosis focuses on Long non-coding RNA(LncRNA).As genomics advances,LncRNA emerges as a potential target for understanding tumor progression and prognosis,offering prospects for biological targeted therapy.Therefore,this study provides new biomarkers and therapeutic targets for LUAD from the perspective of LncRNA.Methods:Gene expression,clinical outcome and gene mutation data of LUAD patients were downloaded from TCGA database.Spearman correlation was used to analyze the correlation between LncRNA and CRG.Univariate Cox,multivariate Cox and LASSO Cox regression analysis were used to construct a prognostic model of Cuproptosis-LncRNAs.GO and KEGG enrichment and immune function analysis were performed on differentially expressed genes between different risk groups.Then,immune escape analysis was performed on LUAD patients with different TIDE score.Finally,drug sensitivity analysis was performed on these differentially expressed genes.Results:A total of 2244 Cuproptosis-LncRNAs were found.Through the application of univariate Cox regression analysis,multivariate Cox regression analysis,and LASSO Cox regression analysis,a prognostic model was developed,integrating 15 Cuproptosis-LncRNAs to assess the risk of mortality.Following that,the model underwent assessment through risk score analysis,Kaplan-Meier survival analysis,risk distribution,and evaluation of survival outcomes.The results revealed an AUC value of 0.755 for the model,surpassing the AUC of other clinical pathological features.The results of KEGG analysis showed that the differentially expressed genes in different model groups were mainly involved in Amoebiasis,Fat digestion and absorption,and other signaling pathways.The results of TMB showed that the prognostic model of TMB combined with risk score could well evaluate the prognosis of patients.The TIDE scores did not exhibit a notable distinction between the two risk models.Analysis of drug sensitivity revealed that individuals in the low-risk category demonstrated greater responsiveness to 5-Fluorouracil,Axitinib,Bexarotene,and other drugs compared to those in the high-risk group.Conclusion:Our research offers a valuable reference for predicting the prognosis of LUAD,contributing to a better understanding of the future elucidation of the process and mechanism of Cuproptosis-LncRNAs in LUAD.

Intervention effect of telemedicine on ischemic stroke:a systematic review and meta-analysis

Background:Telemedicine refers to the use of information technology by medical institutions to directly provide diagnostic and therapeutic services to patients outside the healthcare facility.It encompasses various aspects such as remote diagnosis,remote monitoring,remote consultation,and remote outpatient services.Numerous articles have evaluated its role in controlling diseases like hypertension,diabetes,atrial fibrillation,and ischemic stroke.However,the existing literature exhibits varying quality and sample sizes,lacking robust convincing power and systematic effectiveness evaluation.Methods:Following The Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 guidelines,we identified articles on remote medical intervention in ischemic stroke through databases including Web of Science,PubMed,EMBASE,Cochrane Library,CNKI,Weipu,and Wanfang.The search spanned from the inception of the databases to June 30,2022.Two researchers independently assessed literature quality,extracted data,and conducted meta-analysis using RevMan 5.3 software.Results:Ten articles,involving 5092 patients,were included.Meta-analysis results indicate that telemedicine can effectively enhance compliance with doctors’advice in ischemic stroke patients.Telemedicine is also associated with reduced stroke recurrence,moderate to severe disability,systolic and diastolic blood pressure,National Institutes of Health Stroke Scale scores,and Modified Rankin Scale scores.Additionally,telemedicine demonstrates effectiveness in improving Fugl-Meyer motor function assessment and the Barthel Index of activity of daily living in ischemic stroke patients.However,telemedicine does not significantly reduce stroke hospitalization in the past year and the death rate.Conclusion:In comparison to traditional healthcare,telemedicine exhibits advantages in improving compliance and enhancing functionality in ischemic stroke patients.It is worth promoting telemedicine for better management of ischemic stroke patients.However,this study does not explain how telemedicine improves the functionality of ischemic stroke patients,indicating a need for further research.

Association of age at diagnosis of diabetes with subsequent risk of age-related ocular diseases and vision acuity

BACKGROUND The importance of age on the development of ocular conditions has been reported by numerous studies.Diabetes may have different associations with different stages of ocular conditions,and the duration of diabetes may affect the development of diabetic eye disease.While there is a dose-response relationship between the age at diagnosis of diabetes and the risk of cardiovascular disease and mortality,whether the age at diagnosis of diabetes is associated with incident ocular conditions remains to be explored.It is unclear which types of diabetes are more predictive of ocular conditions.AIM To examine associations between the age of diabetes diagnosis and the incidence of cataract,glaucoma,age-related macular degeneration(AMD),and vision acuity.METHODS Our analysis was using the UK Biobank.The cohort included 8709 diabetic participants and 17418 controls for ocular condition analysis,and 6689 diabetic participants and 13378 controls for vision analysis.Ocular diseases were identified using inpatient records until January 2021.Vision acuity was assessed using a chart.RESULTS During a median follow-up of 11.0 years,3874,665,and 616 new cases of cataract,glaucoma,and AMD,respectively,were identified.A stronger association between diabetes and incident ocular conditions was observed where diabetes was diagnosed at a younger age.Individuals with type 2 diabetes(T2D)diagnosed at<45 years[HR(95%CI):2.71(1.49-4.93)],45-49 years[2.57(1.17-5.65)],50-54 years[1.85(1.13-3.04)],or 50-59 years of age[1.53(1.00-2.34)]had a higher risk of AMD independent of glycated haemoglobin.T2D diagnosed<45 years[HR(95%CI):2.18(1.71-2.79)],45-49 years[1.54(1.19-2.01)],50-54 years[1.60(1.31-1.96)],or 55-59 years of age[1.21(1.02-1.43)]was associated with an increased cataract risk.T2D diagnosed<45 years of age only was associated with an increased risk of glaucoma[HR(95%CI):1.76(1.00-3.12)].HRs(95%CIs)for AMD,cataract,and glaucoma associated with type 1 diabetes(T1D)were 4.12(1.99-8.53),2.95(2.17-4.02),and 2.40(1.09-5.31),respectively.In multivariable-adjusted analysis,individuals with T2D diagnosed<45 years of age[β95%CI:0.025(0.009,0.040)]had a larger increase in LogMAR.Theβ(95%CI)for LogMAR associated with T1D was 0.044(0.014,0.073).CONCLUSION The younger age at the diagnosis of diabetes is associated with a larger relative risk of incident ocular diseases and greater vision loss.

Machine learning identifies the risk of complications after laparoscopic radical gastrectomy for gastric cancer

BACKGROUND Laparoscopic radical gastrectomy is widely used,and perioperative complications have become a highly concerned issue.AIM To develop a predictive model for complications in laparoscopic radical gastrectomy for gastric cancer to better predict the likelihood of complications in gastric cancer patients within 30 days after surgery,guide perioperative treatment strategies for gastric cancer patients,and prevent serious complications.METHODS In total,998 patients who underwent laparoscopic radical gastrectomy for gastric cancer at 16 Chinese medical centers were included in the training group for the complication model,and 398 patients were included in the validation group.The clinicopathological data and 30-d postoperative complications of gastric cancer patients were collected.Three machine learning methods,lasso regression,random forest,and artificial neural networks,were used to construct postoperative complication prediction models for laparoscopic distal gastrectomy and laparoscopic total gastrectomy,and their prediction efficacy and accuracy were evaluated.RESULTS The constructed complication model,particularly the random forest model,could better predict serious complications in gastric cancer patients undergoing laparoscopic radical gastrectomy.It exhibited stable performance in external validation and is worthy of further promotion in more centers.CONCLUSION Using the risk factors identified in multicenter datasets,highly sensitive risk prediction models for complications following laparoscopic radical gastrectomy were established.We hope to facilitate the diagnosis and treatment of preoperative and postoperative decision-making by using these models.

Joint Detection of Serum Vitamin D,Body Mass Index,and Tumor Necrosis Factor Alpha for the Diagnosis of Crohn’s Disease

Objective Vitamin D(VD)deficiency was reported to contribute to the progression of Crohn’s disease(CD)and affect the prognosis of CD patients.This study investigated the role of serum VD,body mass index(BMI),and tumor necrosis factor alpha(TNF-α)in the diagnosis of Crohn’s disease.Methods CD patients(n=76)and healthy subjects(n=76)were enrolled between May 2019 and December 2020.The serum 25-hydroxyvitamin D[25(OH)D]levels,BMI,and TNF-αlevels,together with other biochemical parameters,were assessed before treatment.The diagnostic efficacy of the single and joint detection of serum 25(OH)D,BMI,and TNF-αwas determined using receiver operating characteristic(ROC)curves.Results The levels of 25(OH)D,BMI,and nutritional indicators,including hemoglobin,total protein,albumin,and high-density lipoprotein cholesterol,were much lower,and the TNF-αlevels were much higher in the CD patients than in the healthy subjects(P<0.05 for all).The areas under the ROC curve for the single detection of 25(OH)D,BMI,and TNF-αwere 0.887,0.896,and 0.838,respectively,with the optimal cutoff values being 20.64 ng/mL,19.77 kg/m^(2),and 6.85 fmol/mL,respectively.The diagnostic efficacy of the joint detection of 25(OH)D,BMI,and TNF-αwas the highest,with an area under the ROC curve of 0.988(95%CI:0.968–1.000).Conclusion The joint detection of 25(OH)D,TNF-α,and BMI showed high sensitivity,specificity,and accuracy in CD diagnosis;thus,it would be effective for the diagnosis of CD in clinical practice.

Bilateral U-Net semantic segmentation with spatial attention mechanism

Aiming at the problem that the existing models have a poor segmentation effect on imbalanced data sets with small-scale samples,a bilateral U-Net network model with a spatial attention mechanism is designed.The model uses the lightweight MobileNetV2 as the backbone network for feature hierarchical extraction and proposes an Attentive Pyramid Spatial Attention(APSA)module compared to the Attenuated Spatial Pyramid module,which can increase the receptive field and enhance the information,and finally adds the context fusion prediction branch that fuses high-semantic and low-semantic prediction results,and the model effectively improves the segmentation accuracy of small data sets.The experimental results on the CamVid data set show that compared with some existing semantic segmentation networks,the algorithm has a better segmentation effect and segmentation accuracy,and its mIOU reaches 75.85%.Moreover,to verify the generality of the model and the effectiveness of the APSA module,experiments were conducted on the VOC 2012 data set,and the APSA module improved mIOU by about 12.2%.

Cardiopulmonary prognosis of prophylactic endotracheal intubation in patients with upper gastrointestinal bleeding undergoing endoscopy

BACKGROUND:It is controversial whether prophylactic endotracheal intubation(PEI)protects the airway before endoscopy in critically ill patients with upper gastrointestinal bleeding(UGIB).The study aimed to explore the predictive value of PEI for cardiopulmonary outcomes and identify high-risk patients with UGIB undergoing endoscopy.METHODS:Patients undergoing endoscopy for UGIB were retrospectively enrolled in the eICU Collaborative Research Database(eICU-CRD).The composite cardiopulmonary outcomes included aspiration,pneumonia,pulmonary edema,shock or hypotension,cardiac arrest,myocardial infarction,and arrhythmia.The incidence of cardiopulmonary outcomes within 48 h after endoscopy was compared between the PEI and non-PEI groups.Logistic regression analyses and propensity score matching analyses were performed to estimate effects of PEI on cardiopulmonary outcomes.Moreover,restricted cubic spline plots were used to assess for any threshold effects in the association between baseline variables and risk of cardiopulmonary outcomes(yes/no)in the PEI group.RESULTS:A total of 946 patients were divided into the PEI group(108/946,11.4%)and the non-PEI group(838/946,88.6%).After propensity score matching,the PEI group(n=50)had a higher incidence of cardiopulmonary outcomes(58.0%vs.30.3%,P=0.001).PEI was a risk factor for cardiopulmonary outcomes after adjusting for confounders(odds ratio[OR]3.176,95%confidence interval[95%CI]1.567-6.438,P=0.001).The subgroup analysis indicated the similar results.A shock index>0.77 was a predictor for cardiopulmonary outcomes in patients undergoing PEI(P=0.015).The probability of cardiopulmonary outcomes in the PEI group depended on the Charlson Comorbidity Index(OR 1.465,95%CI 1.079-1.989,P=0.014)and shock index>0.77(compared with shock index≤0.77[OR 2.981,95%CI 1.186-7.492,P=0.020,AUC=0.764]).CONCLUSION:PEI may be associated with cardiopulmonary outcomes in elderly and critically ill patients with UGIB undergoing endoscopy.Furthermore,a shock index greater than 0.77 could be used as a predictor of a worse prognosis in patients undergoing PEI.

IgG4-related kidney disease complicated with retroperitoneal fibrosis:A case report

BACKGROUND IgG4-related disease(IgG4-RD)is a chronic fibrotic disease mediated by immunity recognized by clinicians in recent years.When the kidney is involved,it is called IgG4-related kidney disease(IgG4-RKD).IgG4-related tubulointerstitial nephritis(IgG4-TIN)is a representative manifestation of IgG4-RKD.IgG4-TIN can cause obstructive nephropathy complicated by retroperitoneal fibrosis(RPF).Cases of IgG4-TIN complicated with RPF are rare.Glucocorticoids are the firstline therapeutic medication for IgG4-RD and can significantly improve renal function.CASE SUMMARY Herein,we report the case of a 56-year-old man with IgG4-RKD complicated with RPF.The patient presented to the hospital with complaints of elevated serum creatinine(Cr),nausea,and vomiting.During hospitalization,Cr was 1448.6μmol/L,and serum IgG4 was increased.A total abdominal computed tomography(CT)scan and enhanced CT scan obviously indicated RPF.Although this patient had a long course and renal insufficiency,we performed a kidney biopsy.Renal biopsy showed that the renal tubulointerstitium had focal plasma cell infiltration and increased lymphocyte infiltration accompanied by fibrosis.After combining the biopsy results with immunohistochemistry,it was found that the absolute number of positive IgG4+cells per high power field exceeded 10,and the ratio of IgG4/IgG was over 40%.Finally,the patient was diagnosed with IgG4-TIN complicated with RPF and given glucocorticoids as long-term maintenance therapy,helping him keep out of dialysis.After a follow-up of 19 mo,the patient had recovered well.Previous literature on IgG4-RKD and RPF was retrieved from PubMed to characterize the clinical and pathological features and to identify the diagnosis and treatment of IgG4-RKD.CONCLUSION Our case report demonstrates the clinical characteristics of IgG4-RKD complicated with RPF.Serum IgG4 is a favorable indicator for screening.Performing renal biopsy actively plays a vital role in diagnosis and treatment,even if the patient has a long course and manifests with renal insufficiency.It is remarkable to treat IgG4-RKD with glucocorticoids.Hence,early diagnosis and targeted therapy are essential for reversing renal function and improving extrarenal manifestations in patients with IgG4-RKD.

Effects of combining multiple dose reduction techniques on coronary computed tomography angiography

BACKGROUND Coronary computed tomography angiography(CCTA)is the preferred noninvasive examination method for coronary heart disease.However,the radiation from computed tomography has become a concern since public awareness of radiation hazards continue to increase.AIM To explore the value of multiple dose reduction techniques for CCTA.METHODS Consecutive normal and overweight patients were prospectively divided into two groups:Group A1,patients who received multiple dose reduction scans(n=82);and group A2,patients who received conventional scans(n=39).The scan parameters for group A1 were as follows:Isocentric scan,tube voltage=80 kV,and tube current control using 80%smart milliampere.The scan parameters for group A2 were as follows:Normal position,tube voltage=100 kV,and smart milliampere.RESULTS The average effective doses(EDs)for groups A1 and A2 were 1.13±0.35 and 3.36±1.30 mSv,respectively.There was a statistically significant difference in ED between the two groups(P<0.01).Furthermore,noise was significantly lower,and both signal-to-noise ratio and contrast signal-to-noise ratio were higher in group A2 when compared to group A1(P<0.01).Moreover,the subjective image quality(IQ)scores were excellent in both groups,in which there was no significant difference in subjective IQ score between the two groups(P=0.12).CONCLUSION Multiple dose reduction scan techniques can significantly decrease the ED of patients receiving CCTA examinations for clinical diagnosis.

Impact of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on the mortality in sepsis: A meta-analysis

BACKGROUND The effect of angiotensin-converting enzyme inhibitors(ACEIs)or angiotensin receptor blockers(ARBs)on the mortality of patients with sepsis is not well characterized.AIM To elucidate the association between prior ACEI or ARB exposure and mortality in sepsis.METHODS The PubMed,EMBASE,Web of Science,and Cochrane Library databases were searched for all studies of premorbid ACEI or ARB use and sepsis mortality until November 302019.Two reviewers independently assessed,selected,and ab-stracted data from studies reporting ACEIs or ARBs,sepsis,and mortality.The primary extracted data consisted of premorbid ACEI or ARB exposure,mortality,and general patient data.Two reviewers independently assessed the risk of bias and quality of evidence.RESULTS A total of six studies comprising 281238 patients with sepsis,including 49799 cases with premorbid ACEI or ARB exposure were eligible for analysis.Pre-morbid ACEIs or ARBs exposure decreased the 30-d mortality in patients with sepsis.Moreover,the use of ACEIs or ARBs was associated with approximately a 6%decreased risk of 30-d mortality.CONCLUSION The results of this systematic review suggest that ACEI or ARB exposure prior to sepsis may be associated with reduced mortality.Further high-quality cohort studies and molecular mechanism experiments are required to confirm our results.

Oridonin restores hepatic lipid homeostasis in an LXRa-ATGL/EPT1 axis-dependent manner

Hepatosteatosis is characterized by abnormal accumulation of triglycerides(TG),leading to prolonged and chronic inflammatory infiltration.To date,there is still a lack of effective and economical therapies for hepatosteatosis.Oridonin(ORI)is a major bioactive component extracted from the traditional Chinese medicinal herb Rabdosia rubescens.In this paper,we showed that ORI exerted significant protective effects against hepatic steatosis,inflammation and fibrosis,which was dependent on LXRa signaling.It is reported that LXRa regulated lipid homeostasis between triglyceride(TG)and phosphatidylethanolamine(PE)by promoting ATGL and EPT1 expression.Therefore,we implemented the lipidomic strategy and luciferase reporter assay to verify that ORI contributed to the homeostasis of lipids via the regulation of the ATGL gene associated with TG hydrolysis and the EPT1 gene related to PE synthesis in a LXRadependent manner,and the results showed the TG reduction and PE elevation.In detail,hepatic TG overload and lipotoxicity were reversed after ORI treatment by modulating the ATGL and EPT1 genes,respectively.Taken together,the data provide mechanistic insights to explain the bioactivity of ORI in attenuating TG accumulation and cytotoxicity and introduce exciting opportunities for developing novel natural activators of the LXRa-ATGL/EPT1 axis for pharmacologically treating hepatosteatosis and metabolic disorders.

Infrequent organ involvement in immunoglobulin G4-related prostate disease: A case report

BACKGROUND Immunoglobulin G4-related prostate disease(IgG4-RPD)characterized by a high count of IgG4-positive plasma cells has distinctive serological and radiological findings.Here we report a case of a patient who was successfully treated for IgG4-RPD,which manifested as frequent micturition,dysuric,and systemic lymphadenopathy.CASE SUMMARY The patient was a 33-year-old man who was referred to our hospital because of urinary tract symptoms that had persisted for 4 years.A physical examination revealed systemic lymphadenopathy and blood tests showed hyperglobulinemia with an IgG level of 18.90 g/L and an IgG4 level of 18.40 g/L.Computed tomography(CT)revealed bilateral lacrimal gland,right parotid gland and prostatic enlargement.Based on these findings,IgG4-RD was suspected,and further pathological examination and follow-up results showed expected results.Finally,the patient was diagnosed with IgG4-RPD based on clinical symptoms,pathological examination,therapeutic effects,and follow-up results.He received 50 mg oral prednisolone(the dose was gradually reduced and a low dose was used for long-term maintenance)in combination with cyclophosphamide 1.0 g via an intravenous drip for 6 mo.One year after the treatment was initiated,he was free of urinary or other complaints and his serum IgG4 level normalized.CONCLUSION In IgG4-RPD with severe urinary tract symptoms,radiological findings should be carefully examined.IgG4-RPD prognosis is good because the disease responds well to glucocorticoids.Furthermore,it is urgent for clinicians and pathologists to improve their understanding of IgG4-RPD.

Study on mechanisms and molecular verification of Buyang Huanwu decoction in treating ischemic stroke from the perspective of cuproptosis

Background:Ischemic stroke(IS)is a global health issue and the current treatment options for IS are inadequate.Buyang Huanwu decoction(BHD)has demonstrated effectiveness in treating IS.However,the mechanisms by which BHD treats IS remain unclear,and no studies have been conducted to analyze these mechanisms from the perspective of Cuproptosis.In order to investigate the potential of BHD to intervene in IS through Cuproptosis,this study employed a systematic pharmacological approach and molecular docking verification.Methods:To investigate the mechanism of BHD in treating IS through Cuproptosis,relevant information on the structure,targets,and major biological functions and pathways of compounds related to BHD was collected from databases such as PubChem,PharmMapper,UniProt,and GeneCards.The results were then visualized using Cytoscape3.6.1,Ledock,and pymol software.Results:BHD is composed of 7 Chinese medicines,which contain 82 compounds,including 10 core compounds.These compounds are associated with 241 genes,of which 97 are common to BHD,IS,and Cuproptosis.The 97 common genes,including 10 core genes,are involved in biological processes such as proteolysis,regulation of apoptosis and cholesterol storage,as well as cellular components and molecular functions.The common genes among BHD,IS,and Cuproptosis,including 10 core genes,participate mainly in Kyoto Encyclopedia of Genes and Genomes pathways such as pathways in cancer,PI3K-Akt signaling pathway,and Estrogen signaling pathway.According to molecular docking results,linolenic acid showed good docking scores with 9 out of 10 core genes,except for SRC.13-hydroxy-9,11-octadecadienoic acid also demonstrated good docking scores with EGFR,MAPK14,and F2.Similarly,senkyunone also had good docking scores with EGFR,MAPK14,and F2,all of which had docking energy greater than−5 kcal.Conclusion:In this study,the potential of BHD for treating IS through Cuproptosis and its underlying mechanisms were explored and partially validated through molecular docking.However,due to the limitations of the systems pharmacology research method,further validation through cell experiments,animal experiments,and clinical trials may be necessary to confirm these findings.

Discovering the efficacy and mechanism of Chinese herbal medicine for distal symmetric polyneuropathy via integrating meta-analysis and network pharmacology analysis

Objective Chinese herbal medicine(CHM)has been commonly used in Distal Symmetric Polyneuropathy(DSPN)treatment with satisfactory clinical effects,but the underlying pharmacological mechanism of CHM on DSPN remains unclear.We aimed to identify frequently used clinically effective CHM and its potential pharmacological mechanisms for DSPN by conducting meta-analysis and network pharmacology analysis.Methods We searched both Chinese and English databases from March 1990 to October 2022.Studies that met the inclusion criteria were selected for meta-analysis.After extracting the relevant data,we performed meta-analysis and frequency analysis.The active compounds and predicted targets of high-frequency herbs and DSPN-related targets were extracted from public databases.Then we conducted network construction,Gene Ontology(GO)enrichment,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis to discover the potential pharmacological mechanisms.Results Sixteen articles were selected for meta-analysis,and nine high-frequency CHMs were identified,including Radix Astragali seu Hedysari,Rhizoma Ligustici,Caulis Spatholobi,Radix Salviae Miltiorrhizae,Radix Paeoniae Alba,Flos Carthami,Radix Notoginseng,Radix Rehmanniae Recens,Rhizoma Corydalis.Fourteen hub targets including STAT3,CTNNB1,MAPK14,SRC,AKT1,TP53,EGFR,JUN,RELA,MAPK1,FOS,CCND1,HSP90AA1,MYC,and ten active compounds including Quercetin,Kaempferol,Luteolin,Apigenin,beta-sitosterol,Stigmasterol,Caffeic Acid,Aeginetic Acid,Vanillin,and Lauric Acid were identified by network analysis.Enrichment analysis showed that the biological process of hub targets included transcriptional regulation,cell proliferation,redox processes,apoptosis processes,ERK1 and ERK2 cascades,hypoxia reactions,MAPK cascades,and inflammatory responses.The main signalling pathways included HIF,TNF,and PI3K-AKT pathways.Conclusion Nine herbs were involved in the clinical therapeutic effect of CHM on DSPN treatment,and they may exert an anti-DSPN effect by regulating cell proliferation,apoptosis,and redox processes.