Copper ions are essential for cellular function but can induce cytotoxic effects when dysregulated.This review explores the multifaceted role of copper in cancer metabolism with a focus on the novel concept of cupropt...Copper ions are essential for cellular function but can induce cytotoxic effects when dysregulated.This review explores the multifaceted role of copper in cancer metabolism with a focus on the novel concept of cuproptosis,a regulated form of cell death triggered by copper accumulation.The mechanisms underlying copper homeostasis are detailed,including dietary absorption,systemic distribution,and intracellular utilization.Key transporters,such as copper transporter 1(CTR1)and ATPase copper transporting alpha/b(ATP7A/B),are highlighted.Cancer cells often exhibit elevated copper levels,supporting proliferation and metastasis through pro-tumorigenic pathways.Recent studies have shown that disrupting copper homeostasis can induce cuproptosis,which is characterized by the aggregation of lipoylated mitochondrial proteins and disruption of iron-sulfur cluster biogenesis.Advances in copper-based nanotechnology have enabled targeted delivery of copper to tumors,enhancing therapeutic efficacy through synergistic effects with reactive oxygen species(ROS)generation and immunomodulation.However,the hypoxic tumor microenvironment poses significant challenges by upregulating copper-sequestering proteins and downregulating key cuproptosis mediators.Future directions include integrating multi-omics approaches to identify novel therapeutic targets and developing combination therapies to overcome hypoxia-induced resistance.This review provides a comprehensive overview of copper metabolism in cancer,emphasizing the potential of cuproptosis induction as a powerful strategy for oncologic intervention.展开更多
The most common complication of orthopedic surgery is implant failure, which can result in catastrophic injury and a significant financial burden for patients. Implant failure can be caused by a variety of factors, th...The most common complication of orthopedic surgery is implant failure, which can result in catastrophic injury and a significant financial burden for patients. Implant failure can be caused by a variety of factors, the most common of which are peri–implant infection(or implantrelated infection), excessive inflammatory response which caused pain and aseptic loosening. Orthopedic surgeons now have a variety of options for treating these issues, including revision surgery, which has demonstrated to be effective. If excessive inflammatory reaction caused by the corrosion and peri–implant infection can be avoided, it will be of enormous social benefits. This review will provide a summary of corrosion and the inflammation reactions due to the corrosion and antimicrobial properties of Mg alloy-based implants covering both in vitro and in vivo studies. The strategies on hindering/overcoming the excessive inflammatory response and enhancing the antimicrobial activity are discussed in this review.展开更多
Background:Studies have shown that individuals who receive early treatment for rheumatoid arthritis(RA)are more likely to approach life positively,avoiding joint damage and the need for joint replacement surgery.The d...Background:Studies have shown that individuals who receive early treatment for rheumatoid arthritis(RA)are more likely to approach life positively,avoiding joint damage and the need for joint replacement surgery.The diagnosis of early rheumatoid arthritis(ERA)is crucial for effective treatment and prognosis of patients.Urine,as a diagnostic medium,offers the advantages of non-invasive diagnosis.Urinary metabolites can serve as biomarkers for diagnosis,prognosis,and risk prediction,improving specificity and accuracy.Methods:We recruited 37 ERA patients with a history of less than 3 months and a score of 6,26 osteoarthritis(OA)patients,and 30 healthy controls(HC).Urine samples were collected for 16S rRNA sequencing,and untargeted liquid chromatography-mass spectrometry(LC-MS)was used to detect metabolites.Bioinformatics approaches were employed to identify pathogenic metabolites as specific risk factors for ERA precisely.Results:2-methylnaphthalene was identified as a biomarker for ERA in urine.Prevotella,a major part of the urinary microbiome in ERA patients,exhibited a positive correlation with 2-methylnaphthalene.Notably,there were significant variations in urine metabolites among patients with ERA,OA,and HC.2-Methylnaphthalene was found to be significantly enriched in ERA.Besides,inflammatory factors were elevated in ERA patients.The research further demonstrated a positive correlation between rheumatoid factor(RF),erythrocyte sedimentation rate(ESR),and C-reactive protein(CRP)and the metabolite 2-methylnaphthalene.Conclusion:The urine metabolite 2-methylnaphthalene can be a risk factor for early urinary tract infections and may contribute to accurately screening early-risk metabolites in ERA.展开更多
Recent clinical trials have demonstrated a protective effect in using traditional Chinese medicine Tongxinluo(TXL)capsule to treat atherosclerosis.However,clinical evidence of the effects of TXL treatment on coronary ...Recent clinical trials have demonstrated a protective effect in using traditional Chinese medicine Tongxinluo(TXL)capsule to treat atherosclerosis.However,clinical evidence of the effects of TXL treatment on coronary plaque vulnerability is unavailable.In response,we developed this study to investigate the hypothesis that on the basis of statin therapy,treatment with TXL capsule may stabilize coronary lesions in patients with acute coronary syndrome(ACS).The TXL-CAP study was an investigator-initiated,randomized,double-blind clinical trial conducted across 18 medical centers in China.Patients with ACS aging from 18 to 80 years old who had a non-intervened coronary target lesion with a fibrous cap thickness(FCT)<100μm and lipid arc>90°as defined by optical coherence tomography(OCT)were recruited.A total of 220 patients who met the selection criteria but did not meet the exclusion criteria will be finally recruited and randomized to receive treatment with TXL(n=110)or placebo(n=110)for a duration of 12 months.The primary endpoint was the difference in the minimum FCT of the coronary target lesion between TXL and placebo groups at the end of the 12-month follow-up.Secondary endpoints included:(1)changes of the maximum lipid arc and length of the target plaque,and the percentage of lipid,fibrous,and calcified plaques at the end of the12-month period;(2)the incidence of composite cardiovascular events and coronary revascularization within the 12 months;(3)changes in the grade and scores of the angina pectoris as assessed using the Canadian Cardiovascular Society(CCS)grading system and Seattle angina questionnaire(SAQ)score,respectively;and(4)changes in hs-CRP serum levels.The results of the TXLCAP trial will provide additional clinical data for revealing whether TXL capsules stabilizes coronary vulnerable plaques in Chinese ACS patients.展开更多
Medical ultrasound imaging with Doppler plays an essential role in the diagnosis of vascular disease. This study intended to review the clinical use of "to-and-fro" waveform at duplex Doppler ultrasonography...Medical ultrasound imaging with Doppler plays an essential role in the diagnosis of vascular disease. This study intended to review the clinical use of "to-and-fro" waveform at duplex Doppler ultrasonography(DDU) in the diagnosis of pseudoaneurysms in the arterial vessels of upper and lower extremities, abdominal aorta, carotid and vertebral arteries as well as to review our personal experiences of "to-and-fro" waveform at DDU also. After receiving institutional review board approval, an inclusive literature review was carried out in order to review the scientific foundation of "toand-fro" waveform at DDU and its clinical use in the diagnosis of pseudoaneurysms in various arterial vessels. Articles published in the English language between 2000 and 2013 were evaluated in this review study. Pseudoaneurysms in arterial vessels of the upper and lower extremities, abdominal aorta, carotid and vertebral arteries characterized by an extraluminal pattern of blood flow, which shows variable echogenicity, interval complexity, and "to-and-fro" flow pattern on color Doppler ultrasonography. In these arterial vessels, Duplex ultrasonography can demonstrate the degree of clotting, pseudoaneurysm communication, the blood flow patterns and velocities. Spectral Doppler applied to pseudoaneurysms lumen revealed systolic and diastolic turbulent blood flow with traditional "toand-fro" waveform in the communicating channel. Accurate diagnosis of pseudoaneurysm by spectral Doppler is based on the documentation of the "to-andfro" waveform. The size of pseudoaneurysm determines the appropriate treatment approach as surgical or conservative.展开更多
Objective:To investigate the expression of survivin in breast cancer cell lines and explore the effect of survivin siRNA on biology behavior of breast cancer cells.Methods:Western blot was performed to detect the expr...Objective:To investigate the expression of survivin in breast cancer cell lines and explore the effect of survivin siRNA on biology behavior of breast cancer cells.Methods:Western blot was performed to detect the expression of survivin in breast cancer cell lines.Eukaryotic expression vector pIRES2-EGFP-Survivin siRNA was constructed and transtected in MCF7 cells with liposome,the efficiency of survivin siRNA was measured by Western blot and RTPCR.Cell proliferation and apoptosis were detected by CCK8 and cell flow respectively.Cell migration and invasion was measured by transwell assay.Results:Survivin was highly expressed in MCF-7.Green fluorescence was found in MCF-7 cells tranfected with survivin siRNA and control siRNA by inverted fluorescence microscopy,the protein and mRNA level of survivin was significantly lower in cells tranfected with survivin siRNA compared with control group.Compared with control group,interfering the expression of survivin by siRNA significantly decreased the proliferation,migration and invasion of MCF-7 cells,the percentage of apoptosis cells was greatly promoted.Conclusions:Interfering the expression of Survivin can inhibit the cell proliferation,migration and invasion,and promot apoptosis in MCF-7.展开更多
Pneumoconiosis,a fatal lung disease caused by dust inhalation and deposition,is one of the leading occupational diseases worldwide[1].The dust is primarily inorganic particles,such as silica particles,coal dust,and as...Pneumoconiosis,a fatal lung disease caused by dust inhalation and deposition,is one of the leading occupational diseases worldwide[1].The dust is primarily inorganic particles,such as silica particles,coal dust,and asbestos fibers.If the diameter of dust is less than 5μm,it is defined as‘respirable dust’that can easily reach the distal airways and alveoli[2].展开更多
Apoptosis is necessary for maintaining the integrity of proliferative tissues, such as epithelial cells of the gastrointestinal system. The role of apoptosis in post mitotic tissues, such as skeletal muscle, is less w...Apoptosis is necessary for maintaining the integrity of proliferative tissues, such as epithelial cells of the gastrointestinal system. The role of apoptosis in post mitotic tissues, such as skeletal muscle, is less well defined. Apoptosis during muscle atrophy occurs in both myonuclei and other muscle cell types. Apoptosis of myonuclei likely contributes to the loss of muscle mass, but the mechanisms underlying this process are largely unknown. Caspase-dependent as well as -independent pathways have been implicated and the mode by which atrophy is induced likely determines the apoptotic mechanisms that are utilized. It remains to be determined whether a decrease in apoptosis will alleviate atrophy and distinct research strategies may be required for different causes of skeletal muscle loss.展开更多
Both pseudocyesis and delusional pregnancy are said to be rare syndromes, but are reported frequently in developing countries. A distinction has been made between the two syndromes, but the line of demarcation is blur...Both pseudocyesis and delusional pregnancy are said to be rare syndromes, but are reported frequently in developing countries. A distinction has been made between the two syndromes, but the line of demarcation is blurred. The aim of this paper is to review recent cases of pseudocyesis/delusional pregnancy in order to learn more about biopsychosocial antecedents. The recent world literature(2000-2014) on this subject(women only) was reviewed, making no distinction between pseudocyesis and delusional pregnancy. Eighty case histories were found, most of them originating in developing countries. Fifty patients had been given a diagnosis of psychosis, although criteria for making the diagnosis were not always clear. The psychological antecedents included ambivalence about pregnancy, relationship issues, and loss. Very frequently, pseudocyesis/delusional pregnancy occurred when a married couple was infertile and living in a pronatalist society. The infertility was attributed to the woman, which resulted in her experiencing substantial distress and discrimination. When antipsychotic medication was used to treat psychotic symptoms in these women, it led to high prolactin levels and apparent manifestations of pregnancy, such as amenorrhea and galactorrhea, thus reinforcing a false conviction of pregnancy. Developing the erroneous belief that one is pregnant is an understandable process, making the delusion of pregnancy a useful template against which to study the evolution of other, less explicable delusions.展开更多
Ankylosing spondylitis(AS) is a chronic inflammatory disease that affects 1% of the general population. As one of the most severe types of spondyloarthropathy, AS affects the spinal vertebrae and sacroiliac joints, ca...Ankylosing spondylitis(AS) is a chronic inflammatory disease that affects 1% of the general population. As one of the most severe types of spondyloarthropathy, AS affects the spinal vertebrae and sacroiliac joints, causing debilitating pain and loss of mobility. The goal of this review is to provide an overview of AS, from the pathophysiological changes that occur as the disease progresses, to genetic factors that are involved with its onset. Considering the high prevalence in the population, and the debilitating life changes that occur as a result of the disease, a strong emphasis is placed on the diagnostic imaging methods that are used to detect this condition, as well as several treatment methods that could improve the health of individuals diagnosed with AS.展开更多
Glycogen storage disease type Ia (GSD-Ia; also called von Gierke disease) is an autosomal recessive disorder of carbohydrate metabolism caused by glucose-6-phosphatase deficiency. There have been many reports describi...Glycogen storage disease type Ia (GSD-Ia; also called von Gierke disease) is an autosomal recessive disorder of carbohydrate metabolism caused by glucose-6-phosphatase deficiency. There have been many reports describing hepatic tumors in GSD patients; however, most of these reports were of hepatocellular adenomas, whereas there are only few reports describing focal nodular hyperplasia (FNH) or hepatocellular carcinoma (HCC). We report a case with GSD-Ia who had undergone a partial resection of the liver for FNH at 18 years of age and in whom moderately differentiated HCC had developed. Preoperative imaging studies, including ultrasonography, dynamic computer tomography (CT) and magnetic resonance imaging, revealed benign and malignant features. In particular, fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT revealed the atypical findings that FDG accumulated at high levels in the non-tumorous hepatic parenchyma and low levels in the tumor. Right hemihepatectomy was performed. During the perioperative period, high-dose glucose and sodium bicarbonate were administered to control metabolic acidosis. He had multiple recurrences of HCC at 10 mo after surgery and was followed-up with transcatheter arterial chemoembolization. The tumor was already highly advanced when it was found by chance; therefore, a careful follow-up should be mandatory for GSD-I patients as they are at a high risk for HCC, similar to hepatitis patients.展开更多
Pain on the body surface can accompany disorders in the deep tissue or internal organs. However, the anatomical and physiological mechanisms are obscure.Here, we provided direct evidence of axon bifurcation in primary...Pain on the body surface can accompany disorders in the deep tissue or internal organs. However, the anatomical and physiological mechanisms are obscure.Here, we provided direct evidence of axon bifurcation in primary C-nociceptive neurons that innervate both the skin and a visceral organ. Double-labeled dorsal root ganglion(DRG) neurons and Evans blue extravasation were observed in 3 types of chemically-induced visceral inflammation(colitis, urocystitis, and acute gastritis) rat models.In the colitis model, mechanical hypersensitivity and spontaneous activity were recorded in vivo from doublelabeled C-nociceptive neurons in S1 or L6 DRGs. These neurons showed significantly enhanced responses to both somatic stimulation and colorectal distension. Our findings suggest that the branching of C-nociceptor axons contribute to cutaneous hypersensitivity in visceral inflammation. Cutaneous hypersensitivity on certain locations of the body surface might serve as an indicator of pathological conditions in the corresponding visceral organ.展开更多
OBJECTIVE To investigate the beneficial effect of berberine(BBR)on atherosclerosisin Apo^(-/-) E mice and explore the underlying mechanisms based on attenuating vascular inflammation and modulating calcification in hu...OBJECTIVE To investigate the beneficial effect of berberine(BBR)on atherosclerosisin Apo^(-/-) E mice and explore the underlying mechanisms based on attenuating vascular inflammation and modulating calcification in human umbilical vein endothelial cells(HUVECs) and smooth muscle cells(SMCs).METHODS 48 Apo-/-E mice,at 6-8 weeks old,were randomly allocated into 4 groups:normal,model,bbr and atorvastatin(positive control) groups with 12 mice in each group.They were fed with high-fat diet for 4 weeks except those in Normal group and then treated with indicated drugs orsolvent for another 4 weeks.The morphology and inflammation infiltration of aortic were examined with HE staining.The expression of BMP-2 in aortic was examined by immumohistochemical staining.Blood lipid levels were examined by automatic biochemical analyzer.The expression of IL-6,TNF-α and BMP-2 in serum and tissues was detected by ELISA method.The expression of ALP and the content of calcium were detected by commercially-available kits.HUVEC cells were stimulated with TNF-α and incubated with various concentrations of BBR for 24 h.The contents of intercellular cell adhesion molecule-1(ICAM-1),vascular cell adhesion molecule(VCAM-1),matrix metalloprotein-9(MMP-9) in the culture supernatant were detected by ELISA method.Calcification was induced with β-glycerophosphatein SMC cells and the effect of BBR on the content of calcium was examined.RESULTS 4-week berberine treatment markedly lowered serum TC and LDL-c levels and improved the plaque stability in Apo-/-E mice fed with a high-fat diet(P<0.05 or P<0.01) which was comparable with the effect of atorvastatin.Berberineal so significantly decreased the levels of IL-6 and TNF-α in mice serum and aortic tissues(P<0.05 or P<0.001).Berberine tended to decrease ALP,BMP-2 levels and the content of calcium in mice serum and aortic tissues(P<0.05,P<0.01 or P<0.001) which were not observed in atorvastatin group.Berberine significantly lowered the levels of ICAM-1,VCAM-1,and MMP-9 in TNF-α-stimulated HUVECs.It can also lowered the content of calcium in SMCs.CONCLUSION BBR can profitably regulate the levels of blood lipid in mice fed with a high-fat diet,decrease the injury caused by inflammation,and attenuate vascular calcification.It may improve atherosclerosis and play a role in cardiovascular protection.展开更多
Objective: Human induced pluripotent stem(i PS) cells exhibit great potential for generating functional human cells for medical therapies. In this paper, we report for use of human i PS cells labeled with fluorescent ...Objective: Human induced pluripotent stem(i PS) cells exhibit great potential for generating functional human cells for medical therapies. In this paper, we report for use of human i PS cells labeled with fluorescent magnetic nanoparticles(FMNPs) for targeted imaging and synergistic therapy of gastric cancer cells in vivo. Methods: Human i PS cells were prepared and cultured for 72 h. The culture medium was collected, and then was coincubated with MGC803 cells. Cell viability was analyzed by the MTT method. FMNP-labeled human i PS cells were prepared and injected into gastric cancer-bearing nude mice. The mouse model was observed using a small-animal imaging system. The nude mice were irradiated under an external alternating magnetic field and evaluated using an infrared thermal mapping instrument. Tumor sizes were measured weekly. Results: iP S cells and the collected culture medium inhibited the growth of MGC803 cells. FMNP-labeled human iP S cells targeted and imaged gastric cancer cells in vivo, as well as inhibited cancer growth in vivo through the external magnetic field. Conclusion: FMNP-labeled human i PS cells exhibit considerable potential in applications such as targeted dual-mode imaging and synergistic therapy for early gastric cancer.展开更多
Carpal tunnel syndrome(CTS) is the most commonly diagnosed disabling condition of the upper extremities. It is the most commonly known and prevalent type of peripheral entrapment neuropathy that accounts for about 90%...Carpal tunnel syndrome(CTS) is the most commonly diagnosed disabling condition of the upper extremities. It is the most commonly known and prevalent type of peripheral entrapment neuropathy that accounts for about 90% of all entrapment neuropathies. This review aims to provide an outline of CTS by considering anat-omy, pathophysiology, clinical manifestation, diagnostic modalities and management of this common condition, with an emphasis on the diagnostic imaging evaluation.展开更多
Objective:To clone the virB12 gene in pET28a expression vector for production of recombinant protein to be used as antigenic component for future serological test development.Methods: Brucella melitensis(B.melitensis)...Objective:To clone the virB12 gene in pET28a expression vector for production of recombinant protein to be used as antigenic component for future serological test development.Methods: Brucella melitensis(B.melitensis) 16M strain was cultured and bacterial DNA was extracted by Bioneer AccuPrep~ Genomic DNA Extraction Kit.Oligonucleotide primer pair was designed based on Brucella virB12 gene sequence with BamHI and HindIII restriction site at 5’ end of the forward and reverse primers,respectively.DNA amplification was performed using PrimSTAR~ HS DNA polymerase and the PCK product was purified by DNA AccuPrepGel Purification Kit.Purified DNA was cloned into pJET1.2 cloning vector.VirB12 gene fragment was excised from pJET1.2 asing BamHI/HindIII and subsequendy subcloned into pET28a(+).Results:Brucella virB12 gene was successfully cloned in pJET1.2 and then in pET28a(+) plasmids.PCR and restriction enzyme digestion confirms the procedure.Conclusion:We cloned and expressed the Brucella virB12 gene which could be used as antigenic component for specific serological assay development.展开更多
Polylactic acid(PLA)possesses good mechanical and biodegradability properties which make it a suitable material for polymer composites whereas brittleness and high costs limit its utilization in various applications.T...Polylactic acid(PLA)possesses good mechanical and biodegradability properties which make it a suitable material for polymer composites whereas brittleness and high costs limit its utilization in various applications.The reinforcement of natural fibres with biopolymers has been formed to be an efficient technique to develop composites having the ability to be fully biodegradable.This study concerns with the incorporation of various percentages of untreated and alkali-treated Coir Fibres(CF)and pineapple leaf fibres(PALF)in PLA biocomposites and characterizations of flexural,morphological and dynamic mechanical properties.Flexural properties showed that the treated C1P1 hybrid composites(C1P1A)displayed highest flexural strength(35.81 MPa)and modulus(5.28 GPa)among all hybrid biocomposites.Scanning Electron Microscopy(SEM)revealed a behaviour of fibre-matrix adhesion in untreated treated biocomposites.SEM observation revealed good dispersion of the fillers in PLA.Dynamic mechanical analysis revealed that C1P1A showed highest glass transition temperature(Tg)and storage modulus(E')while untreated C3P7 displayed the least Tg and E'.Overall findings showed that alkali-treated hybrid biocomposites(CF/PALF/PLA)especially C1P1A have improved flexural properties,dynamic and morphological properties over untreated biocomposites.Success of these findings will provide attracting consideration of these hybrid biocomposites for various lightweight uses in a broad selection of industrial applications such as biomedical sectors,automobile,construction,electronics equipment,and hardware tools.展开更多
In this study, the distribution of five Alzheimer's disease(AD)-related single nucleotide polymorphisms(SNPs) in the Han population was examined in combination with the evaluation of clinical cognition and brain p...In this study, the distribution of five Alzheimer's disease(AD)-related single nucleotide polymorphisms(SNPs) in the Han population was examined in combination with the evaluation of clinical cognition and brain pathological analysis. The associations among SNPs,clinical daily cognitive states, and postmortem neuropathological changes were analyzed in 110 human brains from the Chinese Academy of Medical Sciences/Peking Union Medical College(CAMS/PUMC) Human Brain Bank.APOE ?4(OR = 4.482, P = 0.004), the RS2305421 GG genotype(adjusted OR = 4.397, P = 0.015), and the RS10498633 GT genotype(adjusted OR = 2.375,P = 0.028) were associated with a higher score on the ABC(Ab plaque score, Braak NFT stage, and CERAD neuritic plaque score) dementia scale. These results advance our understanding of the pathogenesis of AD,the relationship between pathological diagnosis and clinical diagnosis, and the SNPs in the Han population for future research.展开更多
BACKGROUND It is not clear whether sacubitril/valsartan is beneficial for patients with heart failure(HF)with reduced ejec-tion fraction(HFrEF)and low systolic blood pressure(SBP).This study aimed to investigate the e...BACKGROUND It is not clear whether sacubitril/valsartan is beneficial for patients with heart failure(HF)with reduced ejec-tion fraction(HFrEF)and low systolic blood pressure(SBP).This study aimed to investigate the efficacy and tolerability of sacu-bitril/valsartan in HFrEF patients with SBP<100 mmHg.METHODS&RESULTS An observational study was conducted on 117 patients,40.2%of whom had SBP<100 mmHg wit-hout symptomatic hypotension,and 59.8%of whom had SBP≥100 mmHg in an optimized HF follow-up management system.At the 6-month follow-up,52.4%of patients with SBP<100 mmHg and 70.0%of those with SBP≥100 mmHg successfully rea-ched the target dosages of sacubitril/valsartan.A reduction in the concentration of N-terminal pro-B-type natriuretic peptide was similar between patients with SBP<100 mmHg and SBP≥100 mmHg(1627.5 pg/mL and 1340.1 pg/mL,respectively;P=0.75).The effect of sacubitril/valsartan on left ventricular ejection fraction was observed in both SBP categories,with a 10.8%increase in patients with SBP<100 mmHg(P<0.001)and a 14.0%increase in patients with SBP≥100 mmHg(P<0.001).The effects of sac-ubitril/valsartan on SBP were statistically significant and inverse across both SBP categories(P=0.001),with an increase of 7.5 mmHg in patients with SBP<100 mmHg and a decrease of 11.5 mmHg in patients with SBP≥100 mmHg.No statistically signi-ficant differences were observed between the two groups in terms of the occurrence of symptomatic hypotension,deteriorating re-nal function,hyperkalemia,angioedema,or stroke.CONCLUSIONS Within an optimized HF follow-up management system,sacubitril/valsartan exhibited excellent tolerability and prompted left ventricular reverse remodeling in patients with HFrEF who presented asymptomatic hypotension.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.82303206,82372749,and 82072951)Science and Technology Commission of Shanghai Municipality(Grant Nos.20Y11914300 and 22Y21900100)+2 种基金Shanghai Anticancer Association(Grant No.SACAAX202213)Major Research Projects of Taizhou Clinical Medical College(Grant No.TZKY20230308)Natural Science Foundation in University of Jiangsu Province(Grant No.BK20231261).
文摘Copper ions are essential for cellular function but can induce cytotoxic effects when dysregulated.This review explores the multifaceted role of copper in cancer metabolism with a focus on the novel concept of cuproptosis,a regulated form of cell death triggered by copper accumulation.The mechanisms underlying copper homeostasis are detailed,including dietary absorption,systemic distribution,and intracellular utilization.Key transporters,such as copper transporter 1(CTR1)and ATPase copper transporting alpha/b(ATP7A/B),are highlighted.Cancer cells often exhibit elevated copper levels,supporting proliferation and metastasis through pro-tumorigenic pathways.Recent studies have shown that disrupting copper homeostasis can induce cuproptosis,which is characterized by the aggregation of lipoylated mitochondrial proteins and disruption of iron-sulfur cluster biogenesis.Advances in copper-based nanotechnology have enabled targeted delivery of copper to tumors,enhancing therapeutic efficacy through synergistic effects with reactive oxygen species(ROS)generation and immunomodulation.However,the hypoxic tumor microenvironment poses significant challenges by upregulating copper-sequestering proteins and downregulating key cuproptosis mediators.Future directions include integrating multi-omics approaches to identify novel therapeutic targets and developing combination therapies to overcome hypoxia-induced resistance.This review provides a comprehensive overview of copper metabolism in cancer,emphasizing the potential of cuproptosis induction as a powerful strategy for oncologic intervention.
文摘The most common complication of orthopedic surgery is implant failure, which can result in catastrophic injury and a significant financial burden for patients. Implant failure can be caused by a variety of factors, the most common of which are peri–implant infection(or implantrelated infection), excessive inflammatory response which caused pain and aseptic loosening. Orthopedic surgeons now have a variety of options for treating these issues, including revision surgery, which has demonstrated to be effective. If excessive inflammatory reaction caused by the corrosion and peri–implant infection can be avoided, it will be of enormous social benefits. This review will provide a summary of corrosion and the inflammation reactions due to the corrosion and antimicrobial properties of Mg alloy-based implants covering both in vitro and in vivo studies. The strategies on hindering/overcoming the excessive inflammatory response and enhancing the antimicrobial activity are discussed in this review.
基金financially supported by the Natural Science Foundation of China(No.82003766)Taishan Scholars Program(NO.tsqn202211219)+1 种基金the Key Research and Development Project of Shandong Province(No.2021ZDSYS27)Shandong Province nature fund surface project(Grant No.ZR2024MH088)。
文摘Background:Studies have shown that individuals who receive early treatment for rheumatoid arthritis(RA)are more likely to approach life positively,avoiding joint damage and the need for joint replacement surgery.The diagnosis of early rheumatoid arthritis(ERA)is crucial for effective treatment and prognosis of patients.Urine,as a diagnostic medium,offers the advantages of non-invasive diagnosis.Urinary metabolites can serve as biomarkers for diagnosis,prognosis,and risk prediction,improving specificity and accuracy.Methods:We recruited 37 ERA patients with a history of less than 3 months and a score of 6,26 osteoarthritis(OA)patients,and 30 healthy controls(HC).Urine samples were collected for 16S rRNA sequencing,and untargeted liquid chromatography-mass spectrometry(LC-MS)was used to detect metabolites.Bioinformatics approaches were employed to identify pathogenic metabolites as specific risk factors for ERA precisely.Results:2-methylnaphthalene was identified as a biomarker for ERA in urine.Prevotella,a major part of the urinary microbiome in ERA patients,exhibited a positive correlation with 2-methylnaphthalene.Notably,there were significant variations in urine metabolites among patients with ERA,OA,and HC.2-Methylnaphthalene was found to be significantly enriched in ERA.Besides,inflammatory factors were elevated in ERA patients.The research further demonstrated a positive correlation between rheumatoid factor(RF),erythrocyte sedimentation rate(ESR),and C-reactive protein(CRP)and the metabolite 2-methylnaphthalene.Conclusion:The urine metabolite 2-methylnaphthalene can be a risk factor for early urinary tract infections and may contribute to accurately screening early-risk metabolites in ERA.
基金National Key Research and Development Program of China(2017YFC1700502)Ministry of Science and Technology of China。
文摘Recent clinical trials have demonstrated a protective effect in using traditional Chinese medicine Tongxinluo(TXL)capsule to treat atherosclerosis.However,clinical evidence of the effects of TXL treatment on coronary plaque vulnerability is unavailable.In response,we developed this study to investigate the hypothesis that on the basis of statin therapy,treatment with TXL capsule may stabilize coronary lesions in patients with acute coronary syndrome(ACS).The TXL-CAP study was an investigator-initiated,randomized,double-blind clinical trial conducted across 18 medical centers in China.Patients with ACS aging from 18 to 80 years old who had a non-intervened coronary target lesion with a fibrous cap thickness(FCT)<100μm and lipid arc>90°as defined by optical coherence tomography(OCT)were recruited.A total of 220 patients who met the selection criteria but did not meet the exclusion criteria will be finally recruited and randomized to receive treatment with TXL(n=110)or placebo(n=110)for a duration of 12 months.The primary endpoint was the difference in the minimum FCT of the coronary target lesion between TXL and placebo groups at the end of the 12-month follow-up.Secondary endpoints included:(1)changes of the maximum lipid arc and length of the target plaque,and the percentage of lipid,fibrous,and calcified plaques at the end of the12-month period;(2)the incidence of composite cardiovascular events and coronary revascularization within the 12 months;(3)changes in the grade and scores of the angina pectoris as assessed using the Canadian Cardiovascular Society(CCS)grading system and Seattle angina questionnaire(SAQ)score,respectively;and(4)changes in hs-CRP serum levels.The results of the TXLCAP trial will provide additional clinical data for revealing whether TXL capsules stabilizes coronary vulnerable plaques in Chinese ACS patients.
基金Supported by College of Applied Medical Sciences Research Center and the Deanship of Scientific Research at King Saud University,Riyadh,Saudi Arabia
文摘Medical ultrasound imaging with Doppler plays an essential role in the diagnosis of vascular disease. This study intended to review the clinical use of "to-and-fro" waveform at duplex Doppler ultrasonography(DDU) in the diagnosis of pseudoaneurysms in the arterial vessels of upper and lower extremities, abdominal aorta, carotid and vertebral arteries as well as to review our personal experiences of "to-and-fro" waveform at DDU also. After receiving institutional review board approval, an inclusive literature review was carried out in order to review the scientific foundation of "toand-fro" waveform at DDU and its clinical use in the diagnosis of pseudoaneurysms in various arterial vessels. Articles published in the English language between 2000 and 2013 were evaluated in this review study. Pseudoaneurysms in arterial vessels of the upper and lower extremities, abdominal aorta, carotid and vertebral arteries characterized by an extraluminal pattern of blood flow, which shows variable echogenicity, interval complexity, and "to-and-fro" flow pattern on color Doppler ultrasonography. In these arterial vessels, Duplex ultrasonography can demonstrate the degree of clotting, pseudoaneurysm communication, the blood flow patterns and velocities. Spectral Doppler applied to pseudoaneurysms lumen revealed systolic and diastolic turbulent blood flow with traditional "toand-fro" waveform in the communicating channel. Accurate diagnosis of pseudoaneurysm by spectral Doppler is based on the documentation of the "to-andfro" waveform. The size of pseudoaneurysm determines the appropriate treatment approach as surgical or conservative.
基金supported by Scientifie Research Project of Health Department of Sichuan Province(Grant No.140529)
文摘Objective:To investigate the expression of survivin in breast cancer cell lines and explore the effect of survivin siRNA on biology behavior of breast cancer cells.Methods:Western blot was performed to detect the expression of survivin in breast cancer cell lines.Eukaryotic expression vector pIRES2-EGFP-Survivin siRNA was constructed and transtected in MCF7 cells with liposome,the efficiency of survivin siRNA was measured by Western blot and RTPCR.Cell proliferation and apoptosis were detected by CCK8 and cell flow respectively.Cell migration and invasion was measured by transwell assay.Results:Survivin was highly expressed in MCF-7.Green fluorescence was found in MCF-7 cells tranfected with survivin siRNA and control siRNA by inverted fluorescence microscopy,the protein and mRNA level of survivin was significantly lower in cells tranfected with survivin siRNA compared with control group.Compared with control group,interfering the expression of survivin by siRNA significantly decreased the proliferation,migration and invasion of MCF-7 cells,the percentage of apoptosis cells was greatly promoted.Conclusions:Interfering the expression of Survivin can inhibit the cell proliferation,migration and invasion,and promot apoptosis in MCF-7.
基金supported by the CAMS Innovation Fund for Medical Sciences(CIFMS)[No.2018-I2M-1-001]Basic Scientific Research Business Expense Project of Chinese Academy of Medical Sciences[No.20180709]。
文摘Pneumoconiosis,a fatal lung disease caused by dust inhalation and deposition,is one of the leading occupational diseases worldwide[1].The dust is primarily inorganic particles,such as silica particles,coal dust,and asbestos fibers.If the diameter of dust is less than 5μm,it is defined as‘respirable dust’that can easily reach the distal airways and alveoli[2].
基金Supported by NIH/NIA, No.AG20407 NIH/NIAMS, No. AR47577
文摘Apoptosis is necessary for maintaining the integrity of proliferative tissues, such as epithelial cells of the gastrointestinal system. The role of apoptosis in post mitotic tissues, such as skeletal muscle, is less well defined. Apoptosis during muscle atrophy occurs in both myonuclei and other muscle cell types. Apoptosis of myonuclei likely contributes to the loss of muscle mass, but the mechanisms underlying this process are largely unknown. Caspase-dependent as well as -independent pathways have been implicated and the mode by which atrophy is induced likely determines the apoptotic mechanisms that are utilized. It remains to be determined whether a decrease in apoptosis will alleviate atrophy and distinct research strategies may be required for different causes of skeletal muscle loss.
文摘Both pseudocyesis and delusional pregnancy are said to be rare syndromes, but are reported frequently in developing countries. A distinction has been made between the two syndromes, but the line of demarcation is blurred. The aim of this paper is to review recent cases of pseudocyesis/delusional pregnancy in order to learn more about biopsychosocial antecedents. The recent world literature(2000-2014) on this subject(women only) was reviewed, making no distinction between pseudocyesis and delusional pregnancy. Eighty case histories were found, most of them originating in developing countries. Fifty patients had been given a diagnosis of psychosis, although criteria for making the diagnosis were not always clear. The psychological antecedents included ambivalence about pregnancy, relationship issues, and loss. Very frequently, pseudocyesis/delusional pregnancy occurred when a married couple was infertile and living in a pronatalist society. The infertility was attributed to the woman, which resulted in her experiencing substantial distress and discrimination. When antipsychotic medication was used to treat psychotic symptoms in these women, it led to high prolactin levels and apparent manifestations of pregnancy, such as amenorrhea and galactorrhea, thus reinforcing a false conviction of pregnancy. Developing the erroneous belief that one is pregnant is an understandable process, making the delusion of pregnancy a useful template against which to study the evolution of other, less explicable delusions.
文摘Ankylosing spondylitis(AS) is a chronic inflammatory disease that affects 1% of the general population. As one of the most severe types of spondyloarthropathy, AS affects the spinal vertebrae and sacroiliac joints, causing debilitating pain and loss of mobility. The goal of this review is to provide an overview of AS, from the pathophysiological changes that occur as the disease progresses, to genetic factors that are involved with its onset. Considering the high prevalence in the population, and the debilitating life changes that occur as a result of the disease, a strong emphasis is placed on the diagnostic imaging methods that are used to detect this condition, as well as several treatment methods that could improve the health of individuals diagnosed with AS.
文摘Glycogen storage disease type Ia (GSD-Ia; also called von Gierke disease) is an autosomal recessive disorder of carbohydrate metabolism caused by glucose-6-phosphatase deficiency. There have been many reports describing hepatic tumors in GSD patients; however, most of these reports were of hepatocellular adenomas, whereas there are only few reports describing focal nodular hyperplasia (FNH) or hepatocellular carcinoma (HCC). We report a case with GSD-Ia who had undergone a partial resection of the liver for FNH at 18 years of age and in whom moderately differentiated HCC had developed. Preoperative imaging studies, including ultrasonography, dynamic computer tomography (CT) and magnetic resonance imaging, revealed benign and malignant features. In particular, fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT revealed the atypical findings that FDG accumulated at high levels in the non-tumorous hepatic parenchyma and low levels in the tumor. Right hemihepatectomy was performed. During the perioperative period, high-dose glucose and sodium bicarbonate were administered to control metabolic acidosis. He had multiple recurrences of HCC at 10 mo after surgery and was followed-up with transcatheter arterial chemoembolization. The tumor was already highly advanced when it was found by chance; therefore, a careful follow-up should be mandatory for GSD-I patients as they are at a high risk for HCC, similar to hepatitis patients.
基金supported by Grants from the National Science Foundation of China(81771205,91632113,81973963,81674085,and 81674075)the National Key Research and Development Program of China(2018YFC1704600)+1 种基金the Natural Science Foundation and Major Basic Research Program of Shanghai(16JC1420500 and 16JC1420502)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2017-I2M-3-008)。
文摘Pain on the body surface can accompany disorders in the deep tissue or internal organs. However, the anatomical and physiological mechanisms are obscure.Here, we provided direct evidence of axon bifurcation in primary C-nociceptive neurons that innervate both the skin and a visceral organ. Double-labeled dorsal root ganglion(DRG) neurons and Evans blue extravasation were observed in 3 types of chemically-induced visceral inflammation(colitis, urocystitis, and acute gastritis) rat models.In the colitis model, mechanical hypersensitivity and spontaneous activity were recorded in vivo from doublelabeled C-nociceptive neurons in S1 or L6 DRGs. These neurons showed significantly enhanced responses to both somatic stimulation and colorectal distension. Our findings suggest that the branching of C-nociceptor axons contribute to cutaneous hypersensitivity in visceral inflammation. Cutaneous hypersensitivity on certain locations of the body surface might serve as an indicator of pathological conditions in the corresponding visceral organ.
基金supported by National Science Foundation of China(81402943)CAMS Major Collaborative Innovation Project(2016-I2M-1-011)PUMC Youth Fund(3332015168)
文摘OBJECTIVE To investigate the beneficial effect of berberine(BBR)on atherosclerosisin Apo^(-/-) E mice and explore the underlying mechanisms based on attenuating vascular inflammation and modulating calcification in human umbilical vein endothelial cells(HUVECs) and smooth muscle cells(SMCs).METHODS 48 Apo-/-E mice,at 6-8 weeks old,were randomly allocated into 4 groups:normal,model,bbr and atorvastatin(positive control) groups with 12 mice in each group.They were fed with high-fat diet for 4 weeks except those in Normal group and then treated with indicated drugs orsolvent for another 4 weeks.The morphology and inflammation infiltration of aortic were examined with HE staining.The expression of BMP-2 in aortic was examined by immumohistochemical staining.Blood lipid levels were examined by automatic biochemical analyzer.The expression of IL-6,TNF-α and BMP-2 in serum and tissues was detected by ELISA method.The expression of ALP and the content of calcium were detected by commercially-available kits.HUVEC cells were stimulated with TNF-α and incubated with various concentrations of BBR for 24 h.The contents of intercellular cell adhesion molecule-1(ICAM-1),vascular cell adhesion molecule(VCAM-1),matrix metalloprotein-9(MMP-9) in the culture supernatant were detected by ELISA method.Calcification was induced with β-glycerophosphatein SMC cells and the effect of BBR on the content of calcium was examined.RESULTS 4-week berberine treatment markedly lowered serum TC and LDL-c levels and improved the plaque stability in Apo-/-E mice fed with a high-fat diet(P<0.05 or P<0.01) which was comparable with the effect of atorvastatin.Berberineal so significantly decreased the levels of IL-6 and TNF-α in mice serum and aortic tissues(P<0.05 or P<0.001).Berberine tended to decrease ALP,BMP-2 levels and the content of calcium in mice serum and aortic tissues(P<0.05,P<0.01 or P<0.001) which were not observed in atorvastatin group.Berberine significantly lowered the levels of ICAM-1,VCAM-1,and MMP-9 in TNF-α-stimulated HUVECs.It can also lowered the content of calcium in SMCs.CONCLUSION BBR can profitably regulate the levels of blood lipid in mice fed with a high-fat diet,decrease the injury caused by inflammation,and attenuate vascular calcification.It may improve atherosclerosis and play a role in cardiovascular protection.
基金supported by National Natural Science Foundation of China (Grant No. 81225010, 20803040, 81028009, and 31170961)National Key Basic Research Program of China (973 Program) (Grant No. 2010CB933902 and 2015CB931802)+1 种基金National Key Technology Research and Development Program (863 Program) (Grant No. 2012AA022703 and 2014AA020700)Shanghai Science and Technology Fund (Grant No.13NM1401500)
文摘Objective: Human induced pluripotent stem(i PS) cells exhibit great potential for generating functional human cells for medical therapies. In this paper, we report for use of human i PS cells labeled with fluorescent magnetic nanoparticles(FMNPs) for targeted imaging and synergistic therapy of gastric cancer cells in vivo. Methods: Human i PS cells were prepared and cultured for 72 h. The culture medium was collected, and then was coincubated with MGC803 cells. Cell viability was analyzed by the MTT method. FMNP-labeled human i PS cells were prepared and injected into gastric cancer-bearing nude mice. The mouse model was observed using a small-animal imaging system. The nude mice were irradiated under an external alternating magnetic field and evaluated using an infrared thermal mapping instrument. Tumor sizes were measured weekly. Results: iP S cells and the collected culture medium inhibited the growth of MGC803 cells. FMNP-labeled human iP S cells targeted and imaged gastric cancer cells in vivo, as well as inhibited cancer growth in vivo through the external magnetic field. Conclusion: FMNP-labeled human i PS cells exhibit considerable potential in applications such as targeted dual-mode imaging and synergistic therapy for early gastric cancer.
文摘Carpal tunnel syndrome(CTS) is the most commonly diagnosed disabling condition of the upper extremities. It is the most commonly known and prevalent type of peripheral entrapment neuropathy that accounts for about 90% of all entrapment neuropathies. This review aims to provide an outline of CTS by considering anat-omy, pathophysiology, clinical manifestation, diagnostic modalities and management of this common condition, with an emphasis on the diagnostic imaging evaluation.
基金supported by grant from Tehran University of Medical Sciences
文摘Objective:To clone the virB12 gene in pET28a expression vector for production of recombinant protein to be used as antigenic component for future serological test development.Methods: Brucella melitensis(B.melitensis) 16M strain was cultured and bacterial DNA was extracted by Bioneer AccuPrep~ Genomic DNA Extraction Kit.Oligonucleotide primer pair was designed based on Brucella virB12 gene sequence with BamHI and HindIII restriction site at 5’ end of the forward and reverse primers,respectively.DNA amplification was performed using PrimSTAR~ HS DNA polymerase and the PCK product was purified by DNA AccuPrepGel Purification Kit.Purified DNA was cloned into pJET1.2 cloning vector.VirB12 gene fragment was excised from pJET1.2 asing BamHI/HindIII and subsequendy subcloned into pET28a(+).Results:Brucella virB12 gene was successfully cloned in pJET1.2 and then in pET28a(+) plasmids.PCR and restriction enzyme digestion confirms the procedure.Conclusion:We cloned and expressed the Brucella virB12 gene which could be used as antigenic component for specific serological assay development.
基金gratitude to Institute of Tropical Forestry and Forest Products(INTROP),Universiti Putra Malaysia for supporting the funding of research through Grant No:6369108funded by Researchers Supporting Project number(RSP-2021/117),King Saud University,Riyadh,Saudi Arabia.
文摘Polylactic acid(PLA)possesses good mechanical and biodegradability properties which make it a suitable material for polymer composites whereas brittleness and high costs limit its utilization in various applications.The reinforcement of natural fibres with biopolymers has been formed to be an efficient technique to develop composites having the ability to be fully biodegradable.This study concerns with the incorporation of various percentages of untreated and alkali-treated Coir Fibres(CF)and pineapple leaf fibres(PALF)in PLA biocomposites and characterizations of flexural,morphological and dynamic mechanical properties.Flexural properties showed that the treated C1P1 hybrid composites(C1P1A)displayed highest flexural strength(35.81 MPa)and modulus(5.28 GPa)among all hybrid biocomposites.Scanning Electron Microscopy(SEM)revealed a behaviour of fibre-matrix adhesion in untreated treated biocomposites.SEM observation revealed good dispersion of the fillers in PLA.Dynamic mechanical analysis revealed that C1P1A showed highest glass transition temperature(Tg)and storage modulus(E')while untreated C3P7 displayed the least Tg and E'.Overall findings showed that alkali-treated hybrid biocomposites(CF/PALF/PLA)especially C1P1A have improved flexural properties,dynamic and morphological properties over untreated biocomposites.Success of these findings will provide attracting consideration of these hybrid biocomposites for various lightweight uses in a broad selection of industrial applications such as biomedical sectors,automobile,construction,electronics equipment,and hardware tools.
基金supported by grants from the National Natural Science Foundation of China(81271239,81771205,and 91632113)the Institute of Basic Medical Sciences/Chinese Academy of Medical Sciences(CAMS)Dean’s Fund(2011RC01)+1 种基金the CAMS Innovation Fund for Medical Sciences(2016-I2M-1004)the Natural Science Foundation and Major Basic Research Program of Shanghai Municipality,China(16JC1420500 and 16JC1420502)
文摘In this study, the distribution of five Alzheimer's disease(AD)-related single nucleotide polymorphisms(SNPs) in the Han population was examined in combination with the evaluation of clinical cognition and brain pathological analysis. The associations among SNPs,clinical daily cognitive states, and postmortem neuropathological changes were analyzed in 110 human brains from the Chinese Academy of Medical Sciences/Peking Union Medical College(CAMS/PUMC) Human Brain Bank.APOE ?4(OR = 4.482, P = 0.004), the RS2305421 GG genotype(adjusted OR = 4.397, P = 0.015), and the RS10498633 GT genotype(adjusted OR = 2.375,P = 0.028) were associated with a higher score on the ABC(Ab plaque score, Braak NFT stage, and CERAD neuritic plaque score) dementia scale. These results advance our understanding of the pathogenesis of AD,the relationship between pathological diagnosis and clinical diagnosis, and the SNPs in the Han population for future research.
基金supported by the National Natural Science Foundation of China(No.81873516&No.821704-63)the National Key Research and Development Program of China(2021YFF0501404&2021YFF0501403&2017YFC1308303)+1 种基金the Natural Science Foundation of Shandong Province(ZR2019PH030&ZR2019BH052)the China International Medical Foundation(Z-2019-42-1908-2).
文摘BACKGROUND It is not clear whether sacubitril/valsartan is beneficial for patients with heart failure(HF)with reduced ejec-tion fraction(HFrEF)and low systolic blood pressure(SBP).This study aimed to investigate the efficacy and tolerability of sacu-bitril/valsartan in HFrEF patients with SBP<100 mmHg.METHODS&RESULTS An observational study was conducted on 117 patients,40.2%of whom had SBP<100 mmHg wit-hout symptomatic hypotension,and 59.8%of whom had SBP≥100 mmHg in an optimized HF follow-up management system.At the 6-month follow-up,52.4%of patients with SBP<100 mmHg and 70.0%of those with SBP≥100 mmHg successfully rea-ched the target dosages of sacubitril/valsartan.A reduction in the concentration of N-terminal pro-B-type natriuretic peptide was similar between patients with SBP<100 mmHg and SBP≥100 mmHg(1627.5 pg/mL and 1340.1 pg/mL,respectively;P=0.75).The effect of sacubitril/valsartan on left ventricular ejection fraction was observed in both SBP categories,with a 10.8%increase in patients with SBP<100 mmHg(P<0.001)and a 14.0%increase in patients with SBP≥100 mmHg(P<0.001).The effects of sac-ubitril/valsartan on SBP were statistically significant and inverse across both SBP categories(P=0.001),with an increase of 7.5 mmHg in patients with SBP<100 mmHg and a decrease of 11.5 mmHg in patients with SBP≥100 mmHg.No statistically signi-ficant differences were observed between the two groups in terms of the occurrence of symptomatic hypotension,deteriorating re-nal function,hyperkalemia,angioedema,or stroke.CONCLUSIONS Within an optimized HF follow-up management system,sacubitril/valsartan exhibited excellent tolerability and prompted left ventricular reverse remodeling in patients with HFrEF who presented asymptomatic hypotension.
