Implications of Necroptosis for Cardiovascular Diseases

Necroptosis is a non-apoptotic programmed cell death pathway,which causes necrosislike morphologic changes and triggers inflammation in the surrounding tissues.Accumulating evidence has demonstrated that necroptosis is involved in a number of pathological processes that lead to cardiovascular diseases.However,the exact molecular pathways linking them remain unknown.Herein,this review summarizes the necroptosis-related pathways involved in the development of various cardiovascular diseases,including atherosclerosis,cardiac ischemia-reperfusion injury,cardiac hypertrophy,dilated cardiomyopathy and myocardial infarction,and may shed light on the diagnosis and treatment of these diseases.

Short-term environmental enrichment exposure induces proliferation and maturation of doublecortin-positive cells in the prefrontal cortex

Previous studies have demonstrated that doublecortin-positive immature neurons exist pre- dominantly in the superficial layer of the cerebral cortex of adult mammals such as guinea pigs, and these neurons exhibit very weak properties of self-proliferation during adulthood under physiological conditions. To verify whether environmental enrichment has an impact on the proliferation and maturation of these immature neurons in the prefrontal cortex of adult guinea pigs, healthy adult guinea pigs were subjected to short-term environmental enrichment. Animals were allowed to play with various cognitive and physical stimulating objects over a period of 2 weeks, twice per day, for 60 minutes each. Immunofluorescence staining results indicated that the number of doublecortin-positive cells in layer II of the prefrontal cortex was significantly increased after short-term environmental enrichment exposure. In addition, these doublecortin-positive cells co-expressed 5-bromo-2-deoxyuridine （a marker of cell prolifera- tion）, c-Fos （a marker of cell viability） and NeuN （a marker of mature neurons）. Experimental findings showed that short-term environmental enrichment can induce proliferation, activation and maturation of doublecortin-positive cells in layer II of the prefrontal cortex of adult guinea pigs.

Virtual population pharmacokinetic using physiologically based pharmacokinetic model for evaluating bioequivalence of oral lacidipine formulations in dogs

The aim of the present study was to investigate virtual population pharmacokinetic using physiologically based pharmacokinetic(PBPK) model for evaluating bioequivalence of oral lacidipine formulations in dogs. The dissolution behaviors of three lacidipine formulations including one commercial product and two self-made amorphous solid dispersions(ASDs)capsules were determined in 0.07% Tween 80 media. A randomized 3-period crossover design in 6 healthy beagle dogs after oral administration of the three formulations at a single dose of 4 mg was conducted. The PBPK modeling was utilized for the virtual bioequivalence study.In vitro dissolution experiment showed that the dissolution behaviors of lacidipine amorphous solid dispersions(ASDs) capsules, which was respectively prepared by HPMC-E5 or Soluplus, as polymer displayed similar curves compared with the reference formulation in 0.07% Tween 80 media. In vivo pharmacokinetics experiments showed that three formulations had comparable maximum plasma drug concentration(Cmax), and the time(Tmax) to reach Cmax of lacidipine tablet, which was prepared by Soluplus, as polymer was slower than other two formulations in consistency with the in vitro dissolution rate. The 90% confidence interval(CI) for the Cmax, AUC0–24 h and AUC0–∞ of the ratio of the test drug to the reference drug exceeded the acceptable bioequivalence(BE) limits(0.80–1.25). However, the 90% CI of the AUC0–24 h, AUC0–∞ and Cmax of the ratio of test to reference drug were within the BE limit,calculated using PBPK modeling when the virtual subjects reached 24 dogs. The results all demonstrated that virtual bioequivalence study can overcome the inequivalence caused by inter-subject variability of the 6 beagle dogs involved in in vivo experiments.

Simulation study of longitudinal injection scheme for HALS with a higher harmonic cavity system

Longitudinal injection is a promising on-axis injection scheme for diffraction-limited storage rings. In the latest version of the Hefei advanced light source (HALS), both the dynamic aperture and momentum aperture have been optimized. A longitudinal injection scheme was investigated on the HALS using a doublefrequency radio frequency system. To evaluate the injection performance, various errors were considered. A series of tracking simulations were conducted, and the injection efficiency was obtained under different error levels.

Diabetes mellitus may affect the long-term survival of hepatitis B virus-related hepatocellular carcinoma patients after liver transplantation

AIM to determine whether diabetes mellitus(DM) affects prognosis/recurrence after liver transplantation(Lt) for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC). METHODS A retrospective study was conducted between January 2000 and August 2013 on 1631 patients with HBV-related HCC who underwent Lt with antiviral prophylaxis. Patient data were obtained from the China Liver transplant Registry(https://www.cltr.org/). to compare the outcomes and tumor recurrence in the HBV-related HCC patients with or without DM, statistical analyses were conducted using χ2 tests, Mann-Whitney tests, the Kaplan-Meier method, log-rank tests and multivariate step-wise Cox regression analysis. RESULTS Univariate analysis of 1631 patients who underwent Lt found overall 1-, 3- and 5-year survival rates of 79%, 73% and 71% respectively in the DM patients, and 84%, 78% and 76% in the non-DM patients respectively. Overall survival rate differences after Lt between the two groups were significant(P = 0.041), but recurrence-free survival rates were not(P = 0.096). By stratified analysis, the overall survival rates in DM patients for age > 50 years(P = 0.002), the presence of vascular invasion(P = 0.096), tumors ≤ 3 cm(P = 0.047), two to three tumor nodules(P = 0.007), Child-Pugh grade B(P = 0.018), and preLt alanine aminotransferase levels between 40 and 80 IU/L(P = 0.017) were significantly lower than in non-DM patients. Additionally, serum α-fetoprotein level > 2000 ng/m L(P = 0.052) was associated with a significant survival difference trend between DM and non-DM patients. Multivariate analysis showed that the presence of DM(P < 0.001, HR = 1.591; 95%CI: 1.239-2.041) was an independent predictor associated with poor survival after Lt. CONCLUSION HBV-related HCC patients with DM have decreased long-term overall survival and poor Lt outcomes. Prevention strategies for HCC patients with DM are recommended.

Beta-amyloid precursor protein cleavage enzyme-1 expression in adult rat retinal neurons in the early period after lead exposure

Previous studies have reported that non-human primates and rodents exposed to lead during brain development may become dependent on the deposition of pre-determined β-amyloid protein （Aβ）,and exhibit upregulation of β-site amyloid precursor protein expression in old age.However,further evidence is required to elucidate the precise relationship and molecular mechanisms underlying the effects of early lead exposure on excessive Aβ production in adult mammals.The present study investigated the effects of lead exposure on expression of β-amyloid precursor protein cleavage enzyme-1 （BACE-1） in the rat retina and the production of Aβ in early development,using the retina as a window for studying Alzheimer＇s disease.Adult rats were intraocularly injected with different doses of lead acetate （10μmol/L,100μmol/L,1 mmol/L,10 mmol/L and 100 mmol/L）.The results revealed that retinal lead concentration,BACE-1 and its cleavage products β-C-terminal fragment and retina Aβ1-40 were all significantly increased in almost all of the lead exposure groups 48 hours later in a dose-dependent manner.The only exception was the 10μmol/L group.The distribution of BACE-1 in the retina did not exhibit obvious changes,and no distinctive increase in the activation of retinal microglia was apparent.Similarly,retinal synaptophysin expression did not exhibit any clear changes.These data suggest that lead exposure can result in the upregulation of retinal neuron BACE-1 expression in the early period of development and further increase the overproduction of Aβ1-40 in the retina.Our results provided novel insight into the molecular mechanisms underlying environmentally-induced Alzheimer＇s disease.

The correlation between rat retinal nerve fiber layer thickness around optic disc by using optical coherence tomography and histological measurements

·AIM: To explore the correlation between the retinal nerve fiber layer (RNFL) thickness by using optical coherence tomography (OCT) and by histological measurements in normal adult rats and optic nerve transected rats. · METHODS: The RNFL thickness of 36 rats was scanned in a circle 3.46mm far from the optic disc by OCT. The two experimental groups were the normal group ( =20 rats) and the optic nerve transected group ( =16 rats). The latter group included 4 groups ( =4 /group) surviving for 1 day, 3, 5 and 7 days. Then the RNFL thickness of the same retina area was also measured by NF -200 immunohistochemical staining method. Linear regression was used to analyze the correlation between the data obtained from these two methods. ·RESULTS: The RNFL thickness of normal right eyes around optic disc by OCT was 72.35 ±5.71μm and that of the left eyes was 72.65 ±5.88μm ( =0.074). The RNFL thickness of the corresponding histological section by immunohistochemistry was 37.54 ±4.05μm (right eyes) and 37.38 ±4.23μm (left eyes) ( =0.059). There was a good correlation between the RNFL thickness measured by OCT and that measured by histology (R 2 =0.8131). After optic nerve transection, the trend of the RNFL thickness was thinner with the prolonged survival time. The correlation of the thickness detected by the above two methods was approximately (R 2 =0.8265). Value of the RNFL thickness in rats around optic disc measured by OCT was obviously higher than that measured by common histological measurement in normal adult rats and optic nerve transected rats. ·CONCLUSION: The RNFL thickness measured by OCT has a strong correlation with that measured by histological method. Through OCT scanning, we found that the thickness of RNFL gradually becomes thinner in a time-dependent manner.

High expression of protein phosphatase 2 regulatory subunit B''alpha predicts poor outcome in hepatocellular carcinoma patients after liver transplantation

BACKGROUND Protein phosphatase 2 regulatory subunit B''alpha(PPP2R3A)gene has been reported in other tumors,but the influence of PPP2R3A gene expression on the occurrence,development,and prognosis of hepatocellular carcinoma(HCC)remains unclear.AIM To investigate whether the PPP2R3A gene could be used to predict tumor recurrence and survival of HCC patients after liver transplantation(LT).METHODS Diseased liver tissues of HCC patients after LT were collected as well as their clinical data and follow-up information.The immunohistochemical method was used to detect the expression of PPP2R3A protein in the tissues of 108 patients with primary liver cancer.Theχ2 test was used to analyze the relationship between PPP2R3A protein expression levels and the clinicopathological features of tumors.The Kaplan-Meier method was used to analyze overall postoperative survival.The COX proportional hazard model was used to analyze adverse prognostic factors.RESULTS Immunohistochemistry showed that the PPP2R3A protein was mainly expressed in the cytoplasm of HCC cells.Compared to corresponding peritumoral tissues,expression was higher in HCC tissues(P≤0.001).Correlation analysis showed that high PPP2R3A expression was correlated with preoperative serum alphafetoprotein(AFP)levels(P=0.003),tumor-node-metastasis-t stage(P≤0.001),and envelope invasion(P=0.001).Univariate analysis showed that overall survival(P≤0.001)and recurrence-free survival(P=0.025)of patients with high PPP2R3A expression(≥4 points)were poor compared to those with low expression(<4 points).The overall survival rates or recurrence-free survival rates at 1,2,and 3 years with high PPP2R3A expression were 73%,38%,and 23%or 31%,23%,and 23%,respectively.Multivariate analysis showed that high PPP2R3A expression(hazard ratio=2.900,95%confidence interval:1.411–5.960,P=0.004)was an independent survival risk factor of HCC patients after LT,and it was also an independent predictor of postoperative tumor recurrence.This study also showed in patients with AFP≥400 ng/mL,the overall survival(P≤0.001)and recurrencefree survival(P=0.023)of those with high PPP2R3A expression were significantly worse compared to those with low PPP2R3A expression.When PPP2R3A expression was low,the overall survival rate(P=0.461)or recurrence-free survival rate(P=0.072)after LT in patients with AFP<400 ng/mL and≥400 ng/mL was not significantly difference.The 1,2,and 3 year survival rate of patients with low PPP2R3A expression and AFP<400 ng/mL were 98%,80%,and 69%,respectively,while patients who met Hangzhou criteria had a posttransplant 1,2,and 3 years overall survival rate of 89%,66%,and 55%,respectively.CONCLUSION High expression of PPP2R3A might be a potential marker for predicting poor prognosis of HCC after LT.Combined with serum AFP levels,PPP2R3A might enhance the accuracy of predicting HCC outcome in patients after LT and supplement the efficacy of the Hangzhou criteria.

Role of unc5b in retinal neovascularization in mice with oxygen-induced retinopathy

AIM: To explore the role of unc5b in retinal neovascularization in murine oxygen-induced retinopathy (OIR). METHODS: On postnatal 7 (P7), C57BL/6J mice were exposed to 75% +/- 2% oxygen for 5 days. On postnatal 12 (P12), the mice were brought back to the room air (21% oxygen) to induce retinal neovascularization. Western blot analysis was performed to examine the temporal expression of unc5b in murine retinas. Double staining for unc5b and isolectin B4 were employed to determine the location of unc5b in murine retinas. The effect of unc5b on retinal neovascularization was evaluated by intravitreal injection of unc5b-FC in mice with OIR. Retinal neovascularization was measured by counting neovascular cell nuclei above the internal limiting membrane and by angiography of flat-mounted retinas perfused with fluorescein dextran. o RESULTS: Compared to age-matched normal mice, the expression of unc5b was significantly increased in retinas of OIR mice on P17 and P21. Unc5b was apparently expressed in retinal vessels of OIR while being negative in normal retinal vessels. Retinal neovascularization in eyes injected with unc5b-FC was significantly reduced. CONCLUSION: Unc5b-FC can effectively inhibit retinal neovascularization induced by OIR. It may serve as a powerful and novel therapy for ischemia-induced retinal disease.

Simulation of storage ring injection of HLS Ⅱ

The Hefei light source(HLS) has been upgraded into HLS II, with increased brightness and stability. In this paper, the new injection system is described. Elegant program is used to simulate the particles motion in 6D phase space. In the process of tracking simulation of electrons, the system tolerances and magnet errors are introduced. Influences to the injection efficiency from beam injection deviation are studied. These provide important reference for realizing the Top-up injection.

Amino functionalized chiral mesoporous silica nanoparticles for improved loading and release of poorly water-soluble drug

In the present paper, chiral mesoporous silica nano-cocoon(A-CMSN) functionalized with amino group was synthesized, and its loading and release of indomethacin(IMC), a poorly soluble drug, was studied. Due to the use of chiral anionic surfactants as a template, ACMSN possessed 2D hexagonal nano-cocoon morphology with curled channels on its surface, which was quite different from another 2D hexagonal mesoporous silica nanoparticles(MCM-41) with straightway channels. After being loaded into the two silica carriers by hydrogen bond, crystalline IMC converted to amorphous form, leading to the improved drug dissolution. And IMC loading capacity of A-CMSN was higher than MCM-41 because curled loading process originating from curvature chiral channels can hold more drug molecules. Compared with IMC, IMC loaded A-CMSN presented obviously fast release throughout the in vitro release experiment, while IMC loaded MCM-41 released faster than IMC at the initial 5 h then showed controlled slow release afterwards, which was closely related to the mesoporous silica nanoparticles and different channel mesostructures of these two carriers. A-CMSN possessed nano-cocoon morphology with curled 2D hexagonal channel and its channel length was shorter than MCM-41, therefore IMC molecules can easily get rid of the constraint of A-CMSN then to be surrounded by dissolution medium.

System design and measurements of flux concentrator and its solid-state modulator for CEPC positron source

Positron sources are one of the most important components of the injector of a circular electron positron collector(CEPC).The CEPC is designed as an e^(+)e^(−)collider for a Higgs factory.Its accelerator system is composed of 100-km-long storage rings and an injector.The design goal of the positron source is to obtain positron beams with a bunch charge of 3 nC.The flux concentrator(FC)is one of the cores of the positron source.This paper reports the design,development,and measurements of an FC prototype system.The prototype includes an FC and an all-solid-state high-current pulse modulator.Preliminary tests show that the peak current on the FC can reach 15.5 kA,and the peak magnetic field can reach 6.2 T.The test results are consistent with the theoretical simulation.The FC system fulfills the requirements of the CEPC positron source as well as provides a reference for the development of similar devices both domestically and abroad.

Evaluation of pharmacokinetics underlies the collaborated usage of lamivudine and oxymatrine in beagle dogs

Combinational therapy of lamivudine and oxymatrine has been employed in the battle against hepatitis B virus in clinical setting. However, the pharmacokinetic behavior of the drug or active metabolism in intravenous/oral co-administration regime is poorly investigated. Herein,we evaluated the pharmacokinetic characteristic through a tailor-designed 3 way crossoverLatin square experiment in adult male beagle dogs. Six dogs were randomly treated by intravenous administration of lamivudine(2.5 mg/kg), oxymatrine(15 mg/kg) and combinational dosage, named as intravenous regime. Meanwhile the other six dogs were orally administrated with lamivudine(2.5 mg/kg), oxymatrine(15 mg/kg) and combinational dosage,named as oral regime. The pharmacokinetic feature in simultaneous oral treatment appeared to have no significant difference when compared with individual administration,even including matrine, the active metabolite of oxymatrine. In intravenous regime, the main pharmacokinetic parameters of simultaneous administration were nearly consistent with intravenous regime remedy. The collaborated application of lamivudine and oxymatrine contributed to non-distinctive pharmacokinetic fluctuations of beagle dogs in intravenous/oral regime, compared with individual employment, which established a vital base for the clinical co-administration against hepatitis B. Furthermore, the present study demonstrated that the determination of pharmacokinetics between combinational and individual therapy might assist in the development of drug compatibility in clinical therapy.

IgG4 and IgE co-positive group found in idiopathic orbital inflammatory disease

AIM： To reveal the cytokines involved in idiopathic orbital inflammatory disease（IOID） and the relationship between Th17 cells, IgE and IOID pathogenesis.METHODS： Whole blood samples were processed immediately after collection and serological IgG4, IgG, and IgE antibodies were tested using ELISA. IOID and orbital cavernous hemangioma（CH） tissue samples underwent Bio-Plex multiplex cytokine detection. Hematoxylin-Eosin（HE） staining of all paraffin samples suggested the histological features of IOIDs, and expressions of IgG4 and IL-17 A in affected tissues were detected by immunohistochemistry. RESULTS： Among 40 IOID plasma samples, 52.5%（21/40） were positive for IgG4 and 25%（10/40） were positive for IgE. Overlapped IgG4 or IgE positive samples accounted for 22.5%（9/40）. Therefore, IOID samples were separated into three groups. The IgE＋/IgG4＋ group had a relevantly lower level of pro-inflammatory cytokine expression. IL-4（Th2 cell related）, IL-10 and TGF-β1（Treg cell immunity related） were elevated in all three groups. Some of the Th17 cell related cytokines（i.e. IL-17 A/F, IL-25, IL-23, and IL-33） displayed higher expression levels in the IgE-/IgG4-group compared to the other two groups.CONCLUSION： We discovered an IgG4-IgE co-positive group as well as Th17 cell immune involvement in IgG4-IgE co-negative subgtroup in IOID for the first time. The pathogenesis of IOID could differ from different subgroups according to the IgG4 and IgE detection. Therefore, we recommend that, Treatment stratagy should be made according to the clinical assessment of IgG4-IgE and Th17 profile detection.

Performance comparison of the two ICRF antennas in EAST

The experimental advanced superconducting Tokamak has two suits of ion cyclotron radio frequency heating systems, in which the two antennas are of different structures. Their performance is assessed and compared by CST microwave studio. The radiating capacity of antennas and the arcing around them are estimated. The impurity release is analyzed by the radio frequency(RF) potential in the plasma sheath. The simulation results show that the radiating capacity for the folded antenna(I-port) is better than those for the double loops antenna(B-port). However,the folded antenna is worse than the double loops antenna in terms of breakdown. Moreover, the impurity production is relevant to spectrum shaping. The RF potential at(0, π,π, 0) phasing with the peak of spectrum k//= 8.5 m^(-1)is lower than the one with other phases. The impurity is reduced obviously when the folded antenna is powered with(0, π, π, 0) phasing.

水利项目PPP模式风险管理探究

水利工程在国民经济中占有重要地位,水利工程的增多的同时,相关主体也在思考如何运作项目,提高水利工程建设的质量和效率,PPP模式的出现实现了政府、民营资本和私营企业等主体间的联动,加强了项目的建设效果,但是在PPP模式中也因为项目本身的特点及参与主体特点而存在较多的风险。文章对水利项目PPP模式下的风险特点进行分析,并提出风险评价和管控的相关措施。

LSM-YSZ nano-composite cathode with YSZ interlayer for solid oxide fuel cells

Low temperature prepared(La;Sr;);MnO;-δ-Y;Zr;O;（LSM-YSZ） nano-composite cathode has high three-phase boundary（TPB） density and shows higher oxygen reduction reaction（ORR） activity than traditional LSM-YSZ cathode at reduced temperatures. But the weak connection between cathode and electrolyte due to low sintering temperature restrains the performance of LSM-YSZ nano-composite cathode. A YSZ interlayer, consisted of nanoparticles smaller than 10 nm, is introduced by spinning coating hydrolyzed YSZ sol solution on electrolyte and sintering at 800 °C. The thickness of the interlayer is about 150 nm. The YSZ interlayer intimately adheres to the electrolyte and shows obvious agglomeration with LSM-YSZ nano-composite cathode. The power densities of the cell with interlayer are 0.83, 0.46 and 0.21 W/cm;under 0.7 V at 800, 700 and 600 °C, respectively, which are 36%, 48% and 50% improved than that of original cell. The interlayer introduction slightly increases the ohmic resistance but significantly decreases the polarization resistance. The depressed high frequency arcs of impedance spectra suggest that the oxygen incorporation kinetics are enhanced at the boundary of YSZ interlayer and LSM-YSZ nanocomposite cathode, contributing to improved electrochemical performance of the cell with interlayer.

Co/Fe oxide and Ce_(0.8)Gd_(0.2)O_(2-δ) composite interlayer for solid oxide electrolysis cell

A composite interlayer comprised of gadolinia doped ceria（GDC） and Co/Fe oxide was prepared and investigated for solid oxide electrolysis cell with yttrium stabilized zirconia（YSZ） electrolyte and LaSrCoFeO（LSCF） anode. The interlayer was constructed of a base layer of GDC and a top layer of discrete CoO/FeCoOparticles. The presence of the GDC layer drastically alleviated the undesired reactions between LSCF and YSZ, and the presence of Co/Fe oxide led to further performance improvement. At 800 °C and 45% humidity, the cell with 70% Co/Fe-GDC interlayer achieved 0.98 A/cmat 1.18 V, 14% higher than the cell without Co/Fe oxide. Electrochemical impedance spectroscopy（EIS） revealed that with higher Co/Fe content, both the ohmic resistance and the polarization resistance of the cell were reduced. It is suggested that Co/Fe oxide can react with the Sr species segregated from LSCF and Sr（Co,Fe）O, a compound with high catalytic activity and electronic conductivity. The Sr-capturing ability of Co/Fe oxide in combination with the Sr-blocking ability of GDC layer can effectively suppress the undesired reaction between LSCF and YSZ, and consequently improve the cell performance.

Controllable four-wave mixing response in a dual-cavity hybrid optomechanical system

We systematically investigate the four-wave mixing(FWM)spectrum in a dual-cavity hybrid optomechanical system,which is made up of one optical cavity with an ensemble of two-level atoms and another with a mechanical oscillator.In this work,we propose that the hybrid dual-cavity optomechanical system can be employed as a highly sensitive mass sensor due to the fact that the FWM spectrum generated in this system has a narrow spectral width and the intensity of the FWM can be easily tuned by controlling the coupling strength(cavity-cavity,atom-cavity).More fascinatingly,the dual-cavity hybrid optomechanical system can also be used as an all-optical switch in view of the easy on/off control of FWM signals by adjusting the atom-pump detuning to be positive or negative.The proposed schemes have great potential applications in quantum information processing and highly sensitive detection.

Predictive value of alarm symptoms in Rome IV irritable bowel syndrome:A multicenter cross-sectional study

BACKGROUND Irritable bowel syndrome(IBS)is a common functional bowel disease that shares features with many organic diseases and cannot be accurately diagnosed by symptom-based criteria.Alarm symptoms have long been applied in the clinical diagnosis of IBS.However,no study has explored the predictive value of alarm symptoms in suspected IBS patients based on the latest Rome IV criteria.AIM To investigate the predictive value of alarm symptoms in suspected IBS patients based on the Rome IV criteria.METHODS In this multicenter cross-sectional study,we collected data from 730 suspected IBS patients evaluated at 3 tertiary care centers from August 2018 to August 2019.Patients with IBS-like symptoms who completed colonoscopy during the study period were initially identified by investigators through medical records.Eligible patients completed questionnaires,underwent laboratory tests,and were assigned to the IBS or organic disease group according to colonoscopy findings and pathology results(if a biopsy was taken).Independent risk factors for organic disease were explored by logistic regression analysis,and the positive predictive value(PPV)and missed diagnosis rate were calculated.RESULTS The incidence of alarm symptoms in suspected IBS patients was 75.34%.Anemia[odds ratio(OR)=2.825,95%confidence interval(CI):1.273-6.267,P=0.011],fecal occult blood[OR=1.940(95%CI:1.041-3.613),P=0.037],unintended weight loss(P=0.009),female sex[OR=0.560(95%CI:0.330-0.949),P=0.031]and marital status(P=0.030)were independently correlated with organic disease.The prevalence of organic disease was 10.41%in suspected IBS patients.The PPV of alarm symptoms for organic disease was highest for anemia(22.92%),fecal occult blood(19.35%)and unintended weight loss(16.48%),and it was 100%when these three factors were combined.The PPV and missed diagnosis rate for diagnosing IBS were 91.67%and 74.77%when all alarm symptoms were combined with Rome IV and 92.09%and 34.10%when only fecal occult blood,unintended weight loss and anemia were combined with Rome IV,respectively.CONCLUSION Anemia,fecal occult blood and unintended weight loss have high predictive value for organic disease in suspected IBS patients and can help identify patients requiring further examination but are not recommended as exclusion criteria for IBS.