ObjectiveTo investigate the uric acid-lowering effects and mechanisms of acacetin on hyperuricemia （HUA） in mice. MethodsOteracil potassium and adenine were used to establish the mouse model of HUA. Male Kunming mice （n=48） were randomized into six groups： control， model， low-dose （12.5 mg·kg^-1） acacetin， medium-dose （25 mg·kg^-1） acacetin， high-dose （50 mg·kg^-1） acacetin， and allopurinol （10 mg·kg^-1）. Each group received continuous gavage administration for 21 days. An automatic biochemical analyzer was used to measure the levels of uric acid （UA）， creatinine （Cr）， urea nitrogen （BUN）， alanine aminotransferase （ALT） and aspartate aminotransferase （AST）. Additionally， the activity of xanthine oxidase （XOD） in the liver and the levels of tumor necrosis factor （TNF）-α， interleukin （IL）-1β， and IL-18 in the serum were measured by enzyme-linked immunosorbent assay （ELISA）. Pathological changes in the renal tissue were observed by hematoxylin-eosin （HE） staining. Western blot was employed to determine the levels of glucose transporter 9 （GLUT9）， urate transporter 1 （URAT1）， phospho-NF-κB p65 （p-NF-κB p65）， and nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 （NLRP3） in the renal tissue. ResultsCompared with the control group， the model group showed elevated levels of UA， Cr， BUN， ALT， and AST， increased activity of XOD in the liver（P<0.01）， raised levels of TNF-α， IL-1β and IL-18 in the serum（P<0.01）， and significantly up-regulated expression of GLUT9， URAT1， p-NF-κB p65， and NLRP3 in the renal tissue（P<0.01）. Compared with the model group， acacetin reduced the UA level in a dose-dependent manner， significantly improved liver and kidney functions， decreased the XOD activity in the liver， ameliorated the pathological changes in the renal tissue， down-regulated the expression of GLUT9， URAT1， p-NF-κB p65 and NLRP3 in the renal tissue（P<0.01）， and lowered the levels of TNF-α， IL-1β， and IL-18 in the serum（P<0.01）. ConclusionAcacetin can ameliorate HUA by decreasing uric acid production， increasing uric acid excretion， and inhibiting the NF-κB/NLRP3 signaling pathway. Therefore， acacetin may be a potential drug for the treatment of HUA.

OBJECTIVE To prepare an intelligent responsive liposome-hydrogel nanopreparation co-loaded with gambogic acid （GA）， and characterize its antitumor activity in vitro . METHODS GA-ICG-Lip-gel was prepared by ethanol injection and cold dissolution， incorporating GA and the photosensitizer indocyanine green （ICG）. The appearance and microscopic morphology of GA-ICG-Lip-gel were observed， its encapsulation efficiency and drug loading capacity were measured， and its photothermal conversion performance， photothermal stability， and infrared imaging properties were investigated， along with the determination of its in vitro release profile. Human breast cancer MCF-7 cells were used as objects to investigate the effects of GA-ICG-Lip-gel （or with near-infrared light irradiation） on cell viability， migration ability， and the cellular uptake capacity of GA-ICG-Lip-gel. RESULTS GA-ICG-Lip-gel existed in a solution state at room temperature and transformed into a gel state at 37 ℃. Its microstructure was dense with small pores， and its encapsulation efficiency and drug loading were （96.07±0.86） % and （6.28±1.16） %， respectively. After exposure to near-infrared light， the temperature of GA-ICG-Lip-gel rose above 42 ℃， with no significant attenuation observed in the heating curve. The heating efficiency was dependent on both the irradiation time and drug concentration. Compared to media without gelatinase， the cumulative release rate of GA-ICG-Lip-gel increased in media containing gelatinase. In vitro studies showed that GA-ICG-Lip-gel could be efficiently taken up by MCF-7 cells； GA-ICG-Lip-gel significantly inhibited the viability and migration ability of MCF-7 cells （ P ＜0.05）， and this inhibitory effect was further enhanced under near-infrared light irradiation. CONCLUSIONS This study successfully prepares GA-ICG-Lip-gel， which exhibits favorable photothermal conversion properties and temperature/enzyme dual-responsive drug release characteristics， and demonstrates significant inhibitory effects on the proliferation and migration of breast cancer cells.

OBJECTIVE To establish the graded management standards for off-label use of Shenqi fuzheng injection. METHODS Systematic searches were conducted in databases including CNKI， PubMed and the Cochrane Library to retrieve guidelines/consensuses， systematic reviews/meta-analyses， and randomized controlled trials （RCTs） of Shenqi fuzheng injection. The quality of evidence was evaluated using AGREE Ⅱ， AMSTAR Ⅱ， and the Risk of Bias 1.0 tool recommended by Cochrane Collaboration， and the graded management standard for off-label use of Shenqi fuzheng injection was developed by using the Thomson grading system. RESULTS A total of 534 articles were involved， including 11 guidelines， 22 systematic reviews/meta-analysis， and 501 RCTs. They covered 79 off-label indications for Shenqi fuzheng injection： cancer-related fatigue， colorectal cancer and breast cancer， all with high-quality evidence were classified under grade A management （grade Ⅰ commendation）， allowing all physicians across the hospital to prescribe relevant treatments； five diseases， such as ovarian cancer， liver cancer， leukemia， heart failure and cerebral infarction， were classified under grade B management （grade Ⅱa commendation）， with prescription restricted to physicians with intermediate or higher professional titles in specific departments； eleven diseases， including sepsis， cervical cancer， esophageal cancer， etc.， were classified under grade C management （grade Ⅱb commendation）， requiring strict evaluation by senior physicians before prescription； the use of Shenqi fuzheng injection for other conditions was explicitly prohibited due to a lack of sufficient evidence. CONCLUSIONS Off-label use of Shenqi fuzheng injection is prevalent. The graded management standard established by evidence-based medical approach provides a scientific basis for standardizing the clinical application of traditional Chinese medicine injections and offers an operable paradigm for implementing differentiated drug use supervision in medical institutions.

: To analyze the prevalence of anemia and iron deficiency among primary and secondary school students in Rural Nutrition Improvement Program areas of Guizhou Province in 2023, and to explore the related factors, so as to provide evidence for Rural Nutrition Improvement Program optimization. Methods: In September 2023, a stratified random cluster sampling strategy was used to select 40 rural compulsory education schools with rural nutrition improvement program in five counties of Guizhou Province. School level questionnaire was employed to collect information of basic characteristics and school meal implementation. A total of 7 826 primary and secondary school students aged 6-16 underwent anthropometry and hemoglobin (Hb) determination; serum ferritin (SF) was additionally measured in a random subsample of 1 795 pupils. Students in Grade 3 and above also completed a questionnaire covering demographic characteristics, dietary behaviours and nutrition knowledge. Group comparisons were conducted by Chi square test or Fisher s exact test, and multivariable Logistic regression models were constructed to identify factors associated with anemia and iron deficiency. Results: The overall Hb level was (133.21±12.95)g/L, with an anemia prevalence of 7.17%. The overall SF level was (69.58±59.01)μg/L, with an iron deficiency prevalence of 2.73%. Multivariable analysis showed that stunting ( OR =1.88), school menus without nutrient calculation ( OR =1.61) and absence of menu planning software in the current semester ( OR =2.34) independently increased anemia risk, whereas obesity reduced it ( OR =0.54) (all P <0.05). Girls ( OR =4.16) and Grades 7-9 ( OR =5.93) increased iron deficiency risk (both P <0.05). Compared with rarely eating fresh vegetables, students with consuming <3 kinds per day ( OR =0.08) or exactly 3 kinds per day ( OR =0.06) had lower iron deficiency risks (both P <0.05). Conclusions Anemia and iron deficiency are prevalent among primary and secondary school students in Guizhou. Targeted intervention measures should be implemented for key populations to enhance the effectiveness of nutrition improvement program.

OBJECTIVE: To summarize the clinical features and management of two brothers affected with X-linked inhibitor of apoptosis protein (XIAP) deficiency. METHODS: This study retrospectively analyzed the clinical presentations, treatment, and follow-up of two brothers with XIAP deficiency diagnosed at Shanghai Children's Hospital in 2020, and summarized similar cases recorded in databases such as PubMed, Wanfang, Chinese Medical Association Journals, and WIP from January 2006 to November 2024. This study was approved by the Medical Ethics Committee of our hospital (Ethics No.: 2025R128-E01). RESULTS: Patient 1 was the younger brother, who presented at 8 years of age with growth retardation, folliculitis, erythema nodosum, and perineal abscess. Sequencing revealed that he has carried a hemizygous c.566T>C (p.Leu189Pro) variant of the XIAP gene, which was inherited from his mother. He was allergic to infliximab treatment and underwent allogeneic stem cell transplantation (HSCT) in January 2021. During a follow-up of 3 years and 10 months post-transplantation, he showed no gastrointestinal symptoms and had a good outcome. Patient 2 was the elder brother, who presented at 10 years and 6 months of age with growth retardation, rash, and anal fistula. Genetic testing revealed the same variant. He was treated with oral azathioprine but did not have regular follow-ups. At 14-years-and-6-months of age, he had developed severe gastrointestinal infection and hemophagocytic lymphohistiocytosis, which was alleviated after treatment with antibiotics, glucocorticoids, immunoglobulin, and rituximab. He is currently being prepared for HSCT. A total of 13 publications were retrieved, which involved 64 patients from 23 families, with 23 different variants identified. The main clinical manifestations included splenomegaly (34 cases, 53.1%), hemophagocytic lymphohistiocytosis (27 cases, 42.2%), and inflammatory bowel disease or colitis (20 cases, 31.8%). There were significant phenotypic differences among patients from the same family. Thirteen patients (20.3%) underwent HSCT, with a survival rate of 61.5%. CONCLUSION For male children with early onset, poor treatment response, especially those with unexplained splenomegaly and IBD-like symptoms, early genetic testing is recommended. HSCT is a safe and effective treatment for XIAP deficiency. For patients with developmental delay, early onset, and severe IBD phenotype, early transplantation is recommended.
Humans ; Male ; X-Linked Inhibitor of Apoptosis Protein/deficiency* ; Child ; Genetic Diseases, X-Linked/therapy* ; Phenotype ; Siblings ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation

AIM:To observe the effect of dexme-detomidine(DEX)on cerebral ischemia and reperfu-sion(I/R)injury and investigate the possible mecha-nism of nuclear factor erythroid derived 2-like 2(Nrf2)mediated ferroptosis on hippocampal neu-rons.METHODS:The oxygen glucose deprivation/reoxygenation(OGD/R)model in rat primary cul-tured hippocampal neurons was simulated,DEX(50 μmol/L)and Nrf inhibitor BRU(100 nmol/L)were used to observe the changes of ROS levels by DHE fluorescence probe.The middle cerebral ar-tery occlusion model in male SD rats were estab-lished,the degree of neurological impairment was detected by Longa score,and cerebral infarct size was detected by TTC staining.The Fe2+concentra-tion and levels of oxidative stress related factors were detected,oxidative stress and ferroptosis re-lated protein expressions were detected by West-ern blot.RESULTS:The fluorescence intensity of DHE in OGD/R+Dex Group was lower than that in CON group,and the fluorescence intensity of DHE in OGD/R+DEX+BRU group was higher than that in OGD/R+Dex group.Compared with Sham group,the Longa score and cerebral infarct size in I/R group were significantly increased(P＜0.01),the lev-els of SOD,CAT,GSH and GSH-PX were significantly decreased.MDA and Fe2+concentrations were in-creased,the protein expressions of Nrf2,HO-1,GPX4,FTH1 and FPN1 were decreased,and TFR1 protein expression was increased.Compared with I/R group,in DEX+I/R group,the Longa score and ce-rebral infarct size were decreased(P＜0.01),the lev-els of SOD,CAT,GSH and GSH-PX were increased.MDA and Fe2+concentrations were decreased,the protein expressions of Nrf2,HO-1,GPX4,FTH1 and FPN1 were increased,and TFR1 protein expression was decreased.The Nrf2 inhibitor Bru reversed the role of DEX.CONCLUSION:DEX protects against ce-rebral I/R injury through activating Nrf2 signaling pathway and inhibiting ferroptosis in hippocampal neurons.

Heart failure(HF)has become a major global medical burden.Despite the existence of several drugs for the treatment of HF,the progno-sis is still not optimistic,which motivates us to seek new treatments for this disease.Vericiguat,a novel soluble guanylate cyclase(sGC)stimulator,has been approved for use in patients with heart fail-ure.Cardiac remodeling is the important patho-physiological basis of cardiovascular disease occur-rence and development,and closely related to the prognosis of patients.Accumulating evidence sug-gests that vericiguat inhibits cardiac remodeling,but the molecular mechanism remains unclear.Therefore,an in-depth understanding of the molec-ular mechanism of action of vericiguat will be im-portant for future studies of this drug as a poten-tial therapy for slowing the severity of heart fail-ure.This article reviews the mechanism and re-search status of the inhibitory effect of Vericiguat on cardiac remodeling.

Objective To investigate the effects of obesity-related indexes on cardiovascular autonomic nervous function in type 2 diabetes mellitus(T2DM)patients.Methods A total of 421 T2DM patients treated in the Department of Endocrinology of Gansu Provincial People's Hospital were enrolled in this study from October 2020 to October 2023.All the patients were divided into simple T2DM group with VFA<100 cm2(n=193)and obese group with VFA≥100 cm2(OB,n=228)according to visceral fat area(VFA).BMI,waist-to-height ratio(WHtR),waist-to-hip ratio(WHR),lipid accumulation index(LAP),visceral fat index(VAI),Chinese visceral fat index(CVAI),tapeness index(CI),body shape index(ABSI),and body roundness index(BRI)were calculated.Time domain parameters of heart rate variability(HRV)in 24 h holter electrocardiogram were recorded,including the global standard deviation(SDNN)of normal sinus RR interval,standard deviation of mean value of sinus RR interval(SDANN),root mean square difference(RMSSD)of normal continuous sinus RR interval.The percentage of adjacent RR interval difference>50 ms in total interval(PNN50),the HRV triangle index,the standard deviation of the difference of the entire adjacent NN interval length(SDSD).Results Compared with T2DM group,the OB group showed an increase in age,weight,BMI,WC,hip circumference(HC),neck circumference(NC),SBP,HbA1c,TG,SUA,CI,WHtR,WHR,VFA,SFA,VAI,LAP,CVAI,and BRI(P<0.05 or P<0.01),while a decrease in HDL-C(P<0.05).The SDNN,SDANN,SDSD,RMSSD,HRV trigonometric index,and PNN50 were lower in OB group than in T2DM group(P<0.05 or P<0.01).Spearman correlation analysis showed that SDNN and HRV trigonometric index was negatively correlated with age,DM duration,HR,SBP,PWV,WHtR,TG,SUA,VAI,LAP,BRI,VFA,LAP,and CVAI(P<0.05 or P<0.01).Logistic regression analysis shows that age,VFA,and LAP are influencing factors for cardiac autonomic dysfunction.The analysis of the working characteristic curve of the subjects showed that the area under the curve of VFA,age,and LAP in predicting cardiovascular autonomic dysfunction was 0.680,0.614,and 0.577,with sensitivity of 87.5%,41.7%,and 61.8%,and specificity of 47.3%,73.6%,and 55.6%respectively.Conclusions BMI,HC,NC,WC,TG,SFA,CI,WHtR,WHR,LAP,BRI,VAI,CVAI and VFA are closely related to cardiovascular autonomic nervous function in T2DM patients.As VFA,Ageand LAP increase,the risk of cardiovascular autonomic dysfunction increases.

Objective In order to understand the current status and influencing factors of perioperative pulmonary rehabilitation knowledge,attitude,and practice among Chinese thoracic surgery nurses,and to provide references for managers to take targeted measures to improve their pulmonary rehabilitation knowledge,attitude,and practice level.Methods From August to October 2023,a convenience sampling method and cross-sectional descriptive survey were used to anonymously survey 1 167 thoracic surgery nurses from tertiary-level A cancer specialty hospitals and tertiary-level A general hospitals in 24 provinces through the Wenjuanxing platform.A general information questionnaire and a knowledge,attitude and practice questionnaire for lung cancer perioperative pulmonary rehabilitation nurses were used,including knowledge dimension(14 items),belief dimension(6 items),and behavior dimension(14 items),totaling 34 items.Univariate analysis and linear regression multivariate analysis were used to determine the influencing factors of the knowledge,attitude and practice level of thoracic surgery nurses in perioperative pulmonary rehabilitation.Results 1 089 nurses completed the investigation.The total standard score and the dimension scores on knowledge,attitude,and behavior of the perioperative pulmonary rehabilitation questionnaire for thoracic surgery nurses were(80.45±11.84)(73.72±14.68)(89.61±11.38)and(83.46±14.48),respectively.The nature of the hospital,whether there is an administrative position,whether the department carries out ERAS,and whether they have received pulmonary rehabilitation training are the influencing factors of the perioperative pulmonary rehabilitation knowledge,attitude,and practice level of thoracic surgery nurses(P＜0.05).Conclusion The knowledge,attitude,and practice of perioperative lung rehabilitation among thoracic surgery nurses are generally at a moderate level.However,their knowledge of perioperative lung rehabilitation is relatively insufficient,and there are many influencing factors.Managers should strengthen pulmonary rehabilitation training for thoracic surgery nurses,improve their knowledge reserves and evidence conversion capabilities,and coordinate cross-integration among multidisciplinary teams to improve their knowledge,attitude and practice in perioperative pulmonary rehabilitation.

Objective To investigate the relationship between interventricular septal dimensions(IVSd)and urinary albumin/creatinine ratio(UACR)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 757 patients with T2DM hospitalized in the Department of Endocrinology of Gansu Provincial People's Hospital from March 2021 to April 2024 were enrolled in this study.All the patients were divided into T2DM patients without proteinuria(n=388),microproteinuria group(Mic,n=260)and macroproteinuria group(Mac,n=109)according to the UACR levels.General clinical data and biochemical indexes were collected from all the patients.Color Doppler echocardiography was used to record left ventricular ejection fraction(LVEF),left ventricular fraction shortening(LVFS),IVSd,left ventricular posterior wall dimensions(LVPWd),and left atrial diameter(LAD).Pearson correlation analysis was conducted to analyze the correlation between IVSd,LVPWd and related indicators of renal function.Logistic regression analysis was conducted to analyze the influencing factors for T2DM patients with proteinuria.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of the DM duration and IVSd in patients with T2DM and proteinuria.Results The DM duration,SBP,FIns,HbA1c,Scr,24 hUTP,UACR,UAER,IVSd,LVPWd were increased successively(P<0.05),while LVEF and eGFR were decreased successively(P<0.05)in T2DM,Mic,Mac group.Age was higher in Mic group than in T2DM group(P<0.05).DBP and FPG were higher in Mac group than in T2DM and Mic group(P<0.05).Pearson correlation analysis showed that IVSd and LVPWd were positively correlated with 24 hUTP,UACR,UAER and Scr(P<0.05),and negatively correlated with eGFR(P<0.05).Logistic regression analysis indicated that the DM duration and IVSd were significant influencing factors for proteinuria in patients with T2DM.ROC curve showed that the area under ROC curve of IVSd was 0.620,with sensitivity 43.3%and specificity 76.8%,respeictively.Conclusions The DM duration and IVSd are influencing factors for UACR in patients with T2DM.The risk of proteinuria in T2DM patients increases with rising IVSd.