Relationship between Platelet Activation Related Factors and Polymorphism of Related Genes in Patients with Coronary Heart Disease of Blood-stasis Syndrome

Objective： To comparatively study the expressive conditions of platelet activation related factors （GPⅠb, GPⅡb-Ⅲa and GMP-140） in healthy subjects and patients with coronary heart disease （CHD） of blood-stasis （BS） or non-blood-stasis （non-BS） syndrome, and to analyze the relationship between the activities of various glycoproteins and the polymorphism of genes. Methods： With case control design adopted, patients with the CHD （40 of BS, 37 of non-BS） and 39 healthy subjects for control, all fitting to the inclusion criteria, were selected in this study. The number of affected coronary branches was recorded by the contrast examination. The mean fluorescence intensity （MFI） of GPⅠb, GPⅡb-Ⅲa, and GMP-140 （CD42b, CD61, CD62p） in patients and healthy persons was measured with flow cytometry, the polymorphism of HPA-3 gene was detected by Taqman probe technique and that of HPA-2 gene was determined by gene sequencing. Results： MFI of CD61 and CD62p was higher in the CHD patients than in the healthy control, which was also higher in patients of BS syndrome than in patients of non-BS syndrome （P〈0.05）; MFI of CD42b was lower in the CHD patients than in the healthy control （P〈0.05）, but showing insignificant difference between BS and non-BS syndrome （P〉0.05）; at the same time, no significant difference of all the above-mentioned three MFI could be found in patients with various numbers of affected coronary branches, neither in patients with different genotypes at GPⅡb HPA-3 and GPⅠb HPA-2 polymorphism loci （P〉0.05）. Conclusion： （1） The activities of GP Ⅱ b-Ⅲa and GMP-140 were obviously increased in the genesis and developing process of CHD and CHD of BS syndrome, and so they could be taken as one of the objective indexes for microscopic diagnosis of BS syndrome. （2） The level of GPⅠb was lower in CHD patients than in healthy persons, but it was not a sensitive indicator for BS syndrome of CHD. （3） Levels of GP Ⅱb-Ⅲa, GPⅠb and GMP-140 were not related with the number of affected coronary branches in CHD patients. （4） The changes in amino-acids expression induced by the two loci brought no significant influence on GPⅠb and GP Ⅱb-Ⅲa activities.

Expression of T-Helper 17 Cells and Signal Transducers in Patients with Psoriasis Vulgaris of Blood-Heat Syndrome and Blood-Stasis Syndrome

Objective： To investigate the levels of cytokines related to T-helper （Th） 17 cells in serum and signal transducers in the psoriatic lesions of patients with psoriasis vulgaris of blood-heat syndrome （BHS） and blood-stasis syndrome （BSS）. Methods： Sixty patients with psoriasis vulgaris were divided into the BHS and BSS groups according to the syndrome differentiation of Chinese medicine （CM）. Ten healthy subjects were considered as the control group. Cytokine levels of interleukin （IL）-17, IL-23 and IL-6 in serum were determined by enzyme-linked immunosorbent assay. Expression levels of signal transducer and activator of transcription 3 （STAT3）, p38-mitogen-activated protein kinase （MAPK） and STAT6 in the psoriatic lesions were determined using immunohistochemistry （IHC）, Western blot, and real-time quantitative reverse transcription polymerase chain reaction, respectively. Results： Production of IL-17, IL-23 and IL-6 in the BHS group and BSS group were significantly increased compared with those in the control group （P〈0.05）. Levels of IL-17 and IL-23 in the BHS group were higher than those in the BSS group （P〈0.05）. Compared with the control group, IHC positive expressions and protein expressions of STAT3 and p38-MAPK, and the STAT3 mRNA expressions in the BHS and BSS groups were significantly higher （P〈0.05 or P〈0.01）. The protein expression of STAT3 in the BHS group was significantly higher than that in the BSS group （P〈0.05）. Conclusions： Cytokines in serum and signal transducers in the psoriatic lesions alter with various CM syndromes of psoriasis. The results provide scientific basis for the treatment based on syndrome differentiation of CM in treating psoriasis vulgaris.

The Diagnostic Criteria of Blood-Stasis Syndrome:Considerations for Standardization of Pattern Identification

Pattern identification （PI）, also called Bian Zheng （辨证）, syndrome differentiation, pattem diagnosis, or pattem classification, is the basic principle and the key concept of Chinese medicine （CM）. The core of PI is CM syndrome, on which CM theory, therapeutic method, prescribing formula and the use of Chinese herbal medicine are basically based. PI, in fact, is another classification method anticipated to improve the clinical efficacy. How to make an exact PI seems to be very important for taking full advantage of PI in clinical practice. Therefore, the establishment of diagnostic criterion of pattern has been the prerequisite for the standardization of PI. In recent years, a lot of diagnostic criteria of different CM patterns have been formulated. Taking the diagnostic criteria for blood-stasis syndrome as a model, the methodologies and considerations in establishing a pattern diagnostic criterion were discussed in this paper, which might be of great reference value in future PI standardization research.

Differential Expression of MicroRNA in Endothelial Cells Incubated with Serum of Hypertension Patients with Blood-Stasis Syndrome

Objective： To screen out blood-stasis syndrome （BSS）-associated microRNA and therefore determine the possible target for treating hypertension. Methods： A high-energy sequencing method and digital gene expression sequencing theory were adopted to sequence microRNA （miRNA） and messenger RNA （mRNA）, and to determine differential expression in human umbilical vein endothelial cells incubated with serum samples from hypertension patients with or without BSS, and healthy controls. The results were confirmed using gene prediction software. Results： A total of 13 miRNAs and 11 mRNAs showed statistical difference both in the BSS/normal groups and BSS/non-BSS groups, respectively. Four pairs of target mRNNmiRNA were identified： FRMD4Nhsa-miR-34a, MAP3K14/hsa-miR-34a, PER1/hsa-miR-34a, and FGF2/hsa-miR-132. Conclusion： Four mRNNmiRNA pairs mentioned above seem to be involved in pathogenesis and maintenance of hypertension with BSS.

Restless head syndrome:A retrospective study

BACKGROUND Restless legs syndrome(RLS)is characterized by an urge to move with an unpleasant sensation in the lower limbs.RLS typically affects the legs.However,it can also affect several other body regions,such as the arms,abdomen,face,neck,head,and genital area.There are only a few reports of the RLS variant affecting the head.AIM To assess the epidemiological,clinical,and other aspects of the RLS variant affecting the head.METHODS We conducted a retrospective study of 17 adult patients(>18 years)who met the RLS criteria and simultaneously experienced RLS-like symptoms in the head.RESULTS The median age at which symptoms appeared was 41.6 years.Males and females were equally affected(1.1:1).All 17 patients had uncomfortable sensations in the lower legs.Insomnia or disturbed sleep was the most common comorbidity(n=16,88.2%).However,headache was the most common presenting or primary symptom(n=10,70.5%).Dizziness or an abnormal sensation in the head was the second most common presenting symptom(5 patients,29.4%).Other presenting features were leg pain,backache,and generalized body pain.All patients responded favorably to dopaminergic medications.CONCLUSION If RLS-related unpleasant sensations and pain are felt in the head,they may be misinterpreted as headache,dizziness,or psychosomatic symptoms.RLS and headaches in a subset of patients may be two phenotypic manifestations of the same disorder.

Saccharomyces boulardii as a single trigger of food protein-induced enterocolitis syndrome: Seven case reports

BACKGROUND Food protein-induced enterocolitis syndrome(FPIES)is the most serious type of non-immunoglobulin E(IgE)-mediated food allergic reaction manifesting as sepsis-like symptom,which can lead to shock.Saccharomyces boulardii(S.boulardii),a probiotic prescribed frequently in clinical settings,has been reported to trigger FPIES in an infant with soy-triggered FPIES.In this report,we describe a new clinical FPIES in which S.boulardii was the sole triggering factor of acute FPIES adverse reaction in seven healthy infants.CASE SUMMARY Seven FPIES cases triggered by only S.boulardii were gathered from 2011 to the present.None of the patients had previously experienced any allergic reaction to cow’s milk,soy,or complementary food.The age of the patients was 4-10-months old,and the symptoms of FPIES developed after ingestion of S.boulardii,which is mostly prescribed for the treatment of gastroenteritis or antibiotic-associated diarrhea.All patients experienced severe repetitive vomiting 1-3 hours after S.boulardii ingestion.Extreme lethargy,marked pallor,and cyanosis were also observed.No IgE-mediated hypersensitivity developed in any patient.Diarrhea was followed by initial intense vomiting in approximately 5-10 hours after S.boulardii ingestion,and only one case showed bloody,purulent,and foul-smelling diarrhea.The patients stabilized quickly,mostly within 6 hours.Symptoms got all improved within 24 hours after discontinuation of S.boulardii.CONCLUSION S.boulardii can be the sole trigger of acute FPIES and be prescribed cautiously even in healthy children without FPIES.

Health anxiety and work loss in patients diagnosed with serrated polyposis syndrome:A cross sectional study

BACKGROUND Serrated polyposis syndrome(SPS)is a polyposis condition with neoplastic potential,but its psychological impact is not well understood.AIM To assess health anxiety prevalence in a regional Australian cohort of SPS patients and explore factors influencing it,including workforce impacts of regular surveillance.METHODS This cross-sectional study screened patients aged 18-65 undergoing colonoscopy in a regional gastroenterology practice between January 2015 and June 2022.Eligible SPS patients were invited to participate.Data included the Short Health Anxiety Inventory,employment status,and previous demographic and medical findings.RESULTS Health anxiety was found in 21.57%of SPS patients,with anxious patients being significantly more concerned about surveillance(OR=7.70).Patients lost an average of 11.04 work hours per colonoscopy.CONCLUSION Health anxiety in SPS patients aligns with rates in other gastroenterology populations.Identifying it may improve management,though further research is needed to better understand prevalence and care improvements.

Unusual ovarian hyperstimulation syndrome presentation:Pleural effusion without ascites.A case report

BACKGROUND Ovarian hyperstimulation syndrome(OHSS)is a life-threatening complication that can occur in the luteal phase or early pregnancy after controlled ovarian stimulation.This case report highlights a unique manifestation of OHSS involving pleural effusion(PE)in a patient without identifiable risk factors.CASE SUMMARY A 39-year-old woman who underwent controlled ovarian hyperstimulation for an in vitro fertilization(IVF)cycle experienced dyspnea on the eleventh day of post oocyte retrieval.The diagnosis was severe OHSS with a unique manifestation of PE without ascites.Clinical management involved fluid balance and treatment with albumin,furosemide,thromboembolic prophylaxis,and thoracentesis.A continued drainage of the pleural cavity was performed.The patient had a favo-rable outcome,and a dichorionic diamniotic gestation passed without incident.CONCLUSION OHSS and its potential complications can include respiratory distress and PE,as well as thromboembolic disorders.

Anlotinib-induced sick sinus syndrome:Two case reports

BACKGROUND This manuscript describes the first known cases of sick sinus syndrome(SSS)associated with the use of anlotinib in non-small cell lung cancer patients,highlighting the need for increased vigilance and cardiac monitoring.CASE SUMMARY Two patients with non-small cell lung cancer developed SSS after 15 months and 5 months of anlotinib treatment,respectively,presenting with syncope and palpit-ations.Electrocardiogram confirmed SSS,and different treatment approaches were taken for each patient.One patient received a dual-chamber permanent pacemaker,while the other discontinued the medication and experienced symptom resolution.CONCLUSION Anlotinib can induce SSS,suggesting that cardiac monitoring is crucial during anlotinib treatment.Individualized management strategies are necessary for affected individuals.

Magnetic resonance imaging evaluation and nuclear receptor binding SET domain protein 1 mutation in the Sotos syndrome with attention-deficit/hyperactivity disorder

Sotos syndrome is characterized by overgrowth features and is caused by alterations in the nuclear receptor binding SET domain protein 1 gene.Attentiondeficit/hyperactivity disorder(ADHD)is considered a neurodevelopment and psychiatric disorder in childhood.Genetic characteristics and clinical presentation could play an important role in the diagnosis of Sotos syndrome and ADHD.Magnetic resonance imaging(MRI)has been used to assess medical images in Sotos syndrome and ADHD.The images process is considered to display in MRI while wavelet fusion has been used to integrate distinct images for achieving more complete information in single image in this editorial.In the future,genetic mechanisms and artificial intelligence related to medical images could be used in the clinical diagnosis of Sotos syndrome and ADHD.

Cauda equina syndrome with urinary retention as a postoperative complication of lumbar spine surgery:A case report

BACKGROUND Cauda equina syndrome(CES)is characterized by a group of symptoms that may be caused by inflammation,spinal cord compression,venous congestion,or ischemia.This syndrome is commonly an indication for surgical intervention but has not been determined as a postoperative complication following surgery for lumbar spine disease.CASE SUMMARY To report the case of a 54-year-old male patient who had CES following spinal surgery,with no obvious compression lesions found during re-exploration,suggesting that vascular insufficiency may have contributed to the condition.Furthermore,a series of urodynamic studies on bladder recovery patterns in such complications have also been investigated.CONCLUSION Postoperative CES requires urgent imaging and exploration to rule out compression;noncompressive cases,including vascular insufficiency may performed conservative management.

Literature study on traditional Chinese medicine syndromes after renal transplantation

BACKGROUND Kidney transplantation is the most effective means to treat patients with renal failure,but its postoperative problems such as rejection reactions,immunosuppressant poisoning,chronic transplant kidney nephropathy,etc.still have not been effectively solved.This study searched for literature on traditional Chinese medicine(TCM)syndromes after kidney transplantation in China,conducted statistical analysis of the results,and sought to identify the underlying patterns.AIM To understand the TCM syndromes after renal transplantation and associated rules and provide a theoretical basis for further clinical research.METHODS The literature pertaining to TCM syndromes in renal transplantation,published in the China National Knowledge Infrastructure,Wanfang database,and WIP database from 1970 to 2021,was meticulously searched and comprehensively and statistically analyzed.RESULTS Following the established inclusion and exclusion criteria,13 studies were selected for analysis.Post-renal transplantation,no significant discrepancy was noted among the groups based on the location of TCM viscera.However,when categorized according to TCM pathogenic factors,the groups with spleen and kidney yang deficiency,as well as liver and kidney yin deficiency,exhibited a statistically significant difference in the frequency.CONCLUSION Currently,the research on TCM syndromes pertaining to renal transplantation is in its nascent phase.It is imperative to conduct a multicentric,large-scale survey of TCM syndromes subsequent to renal transplantation in the ensuing years.

Pembrolizumab-induced Guillain-Barrésyndrome in triple-negative breast cancer:A case report

BACKGROUND The programmed cell death protein 1 inhibitor pembrolizumab has become a key treatment for various cancers,including triple-negative breast cancer.However,it is associated with immune-related adverse events,including rare but serious neurological complications such as Guillain-Barrésyndrome(GBS).GBS is a potentially life-threatening autoimmune disorder characterized by muscle weakness and paralysis.We present a unique case of pembrolizumab-induced GBS to highlight the importance of recognizing this complication and managing it promptly in patients receiving immune checkpoint inhibitors.CASE SUMMARY A 69-year-old woman with a medical history of hypertension,anxiety,depression,and stage IIIB triple-negative breast cancer treated with pembrolizumab,carboplatin,and paclitaxel,presented to the emergency department with a 1-month history of tingling,lower extremity weakness,and shooting pain.Symptoms progressed to global weakness,ascending paralysis,and double vision.Neurological examination revealed significant lower extremity weakness and sensory deficits.Magnetic resonance imaging of the lumbar spine and cerebrospinal fluid analysis confirmed GBS.Initial treatment with intravenous immunoglobulin led to relapse,requiring additional intravenous immunoglobulin and high-dose glucocorticoids.The patient’s condition improved,pembrolizumab therapy was permanently discontinued,and she was discharged to a rehabilitation facility.CONCLUSION Pembrolizumab can induce GBS,necessitating early recognition,prompt diagnosis,and multidisciplinary management to prevent serious complications.

Cardiovascular involvement in multisystem inflammatory syndrome in children and midterm follow-up from a pediatric tertiary center in India

BACKGROUND In multisystem inflammatory syndrome in children(MIS-C)with coronavirus disease 2019,there was paucity of data from low-income and middle-income countries on cardiovascular involvement and its longitudinal outcomes.We planned to estimate the pattern of cardiovascular involvement among children with MIS-C and its mid-term outcomes.AIM To determine association between cardiovascular abnormalities and clinical and laboratory parameters.To study the time-line for resolution of various abnormalities.METHODS In this prospective study done in a tertiary care hospital,270 were recruited from June 2020 to January 2022.Baseline demographic data and clinical presentation were recorded.Laboratory parameters and echocardiography were done at admission.Follow-up was done at 2 weeks,3 months,6 months and 1 year after diagnosis.Descriptive statistics were used for parametric and non-parametric data.Risk factors were identified by multivariate regression analysis.RESULTS The 211(78.2%)had cardiac involvement and 102 needed intensive care unit(ICU)admission.Cardiovascular abnormalities observed were shock 123(45.6%),coronary dilatation 28(10.4%),coronary aneurysm 77(28.5%),left ventricular(LV)dysfunction 78(29.3%),mitral regurgitation(MR)77(28.5%)and pericardial effusion 98(36.3%).Coronary artery aneurysm/dilatation during follow-up at 2 weeks and 1 year were 25.7%and 0.9%respectively.Multivariate regression analysis revealed breathlessness[odds ratio(OR)=3.91,95%CI:1.25-12.21,P=0.019]and hi-flow nasal cannula(HFNC)support(OR=8.5,95%CI:1.06-68.38,P=0.044)as predictors of cardiovascular involvement.Higher mean age(OR=1.16,95%CI:1.02-1.32,P=0.026),breathlessness(OR=4.99,95%CI:2.05-12.20,P<0.001),gallop(OR=4.45,95%CI:0.41-2.52,P=0.016),MR(OR=3.61,95%CI:1.53-8.53,P=0.004)and invasive ventilation(OR=4.01,95%CI:1.28-12.58,P=0.017)were predictive of LV dysfunction.Altered sensorium(OR=4.96,95%CI:2.23-11.02,P<0.001),headache(OR=6.61,95%CI:1.46-29.92,P=0.014),HFNC(OR=7.03,95%CI:2.04-24.29,P=0.002),non-rebreathing mask usage(OR=21.13,95%CI:9.00-49.61,P<0.001)and invasive ventilation(OR=5.64,95%CI:1.42-22.45,P=0.014)were risk factors for shock.Anemia was a risk factor for coronary involvement(OR=3.09,95%CI:1.79-5.34,P<0.001).CONCLUSION Significant number of children with MIS-C had cardiovascular involvement contributing to higher ICU management.Although shock resolved quickly,resolution of ventricular function and coronary abnormalities were slower,and hence warrants a structured long-term follow-up protocol.

Large-for-size syndrome prophylaxis in infant liver recipients with low body mass

Transplantation of the left lateral section(LLS)of the liver is now an established practice for treating advanced diffuse and unresectable focal liver diseases in children,with variants of the LLS primarily used in infants.However,the surgical challenge of matching the size of an adult donor's graft to the volume of a child's abdomen remains significant.This review explores historical developments,various approaches to measuring the required functional liver mass,and techniques to prevent complications associated with large-for-size grafts in infants.

Research on the Correlation between Platelet Gelsolin and Blood-Stasis Syndrome of Coronary Heart Disease

Objective：To study the distribution of gelsolin in human platelet and plasma,and the association with blood-stasis syndrome（BSS） of coronary heart disease（CHD）.Methods：Sixty patients with CHD（30 in BSS group and 30 in non-BSS group） and 30 healthy subjects（control group） were included in this study.The classification of the syndrome was based on clinical symptoms and signs.Gelsolin concentration in platelet rich plasma（PRP）,platelet poor plasma（PPP）,filamentous actin（F-actin） and group-specific component globulin （Gc-globulin） of PPP were determined by enzyme-linked immunosorbent assay（ELISA）.The fluorescence intensity of CD62p and cytoplasmic calcium（[Ca^（2＋）]_i） in human platelets of patients and healthy persons was measured with flow cytometry.Results：Compared with the control group,gelsolin in PRP of the BSS group increased significantly（P0.01）,while that in PPP of the BSS and non-BSS groups decreased markedly（P0.05）, the CD62p,[Ca^（2＋）]_i of platelet,F-actin,and Gc-globulin of the BSS and non-BSS groups increased significantly （P0.01）.Compared with the non-BSS group,the gelsolin concentration in PRP of BSS group increased significantly（P0.01）,the[Ca^（2＋）]_i of platelet of the BSS group increased markedly（P0.01）,while the F-actin and Gc-globulin of the BSS group had no statistical defference（P0.05）.Conclusions：Gelsolin concentration in PRP was increased and accompanied by the elevated[Ca^（2＋）]_i of platelet in CHD with BSS,while gelsolin in PPP were lowered markedly.We speculate that plasma gelsolin may clear F-actin from circulation,thus resulting in depletion of plasma gelsolin significantly.This,in addition to the increased calcium influx of platelets,may lead to the gelsolin abnormal expression on platelets during the process of BSS in CHD.Therefore,platelet gelsolin may serve as a new potential biomarker and a therapeutic target of BSS in CHD.

Clinical Observation on the Effect of Zengse Pill (增色丸) in Treating Patients with Vitiligo of Qi-stagnancy and Blood-stasis Syndrome Type

Objective： To observe the clinical efficacy of Zengse Pill （增色丸, ZSP） on patients with vitiligo of qi-stagnancy and blood-stasis syndrome type （V-QB）, and to preliminarily explore its mechanism of action. Methods： Sixty-five V-QB patients, with their diagnosis confirmed by clinical examination, were randomized by digital table method into two groups, with 31 patients in the control group and 34 in the treatment group. Cobamamide （2 tablets） was administered orally to all patients, and Psoralea tincture （a self-formulated preparation） was applied externally thrice a day. In addition, for patients in the treatment group, ZSP was given orally, at 5 pills per dose, 3 times every day. The therapeutic course for both groups was 3 months. Patients were re-examined every half-month, and changes in the skin lesions were observed and recorded. The levels of lymphocyte subsets, serum immune globulin, and complement C3 and C4 in patients were determined before and after the therapeutic course and compared with the corresponding indexes determined in 21 healthy subjects, Results： The total effective rate in the treatment group was 82.4%, which was markedly higher than that in the control group （54.8%）, showing a significant difference （P〈O.05）. After treatment, CD4^＋ percentage, CD4^＋/CD8^＋ratio, and blood levels of C3 and C4 increased, while CD8^＋ percentage decreased in the treatment group （P〈0.05 or P〈0.01）. All these indexes remained unchanged in the control group, and the respective comparisons between groups showed significant differences （P〈0.01）. Conclusion： ZSP has a definite clinical effect on the treatment of V-QB but with no evident adverse reactions, and it can increase the CD4^＋ percentage, CD4^＋/CD8^＋ ratio, and the levels of serum C3 and C4, thus regulating the immunity of the organism, which might be one of its mechanisms of action.

Transforming growth factor β1 is a differentially expressed candidate protein of congestive heart failure with Qi-deficiency-blood-stasis syndrome

OBJECTIVE: To investigate the role of tongue coating fluid protein in regulation of congestive heart failure(CHF) in Qi-deficiency-blood-stasis syndrome.METHODS: We studied patients with CHF(3 patients with Qi-deficiency-blood-stasis syndrome and 3 without Qi-deficiency-blood-stasis syndrome) to investigate differentially expressed proteins. We also included a control group. A biotin label-based antibody array was used for testing tongue coating fluid samples from patients. Net-work analysis of these differentially expressed proteins was conducted using the STRING database,which can predict the relations between differentially expressed proteins and CHF with Qi-deficiency-blood-stasis syndrome.RESULTS: A total of seven differentially expressed proteins were identified, and among these, transforming growth factor β1(TGF-β1) gets a particular attention for us has drawn specific attention.Network analysis showed a homologous relationship of TGF-β1 with bone morphogenetic protein15, which is associated with myocardial fibrosis.CONCLUSION: Occurrence and development of CHF may result from certain DE-proteins and associated signaling pathways. TGF-β1 protein may be a candidate marker for assessing the risk of CHF in Qideficiency-blood-stasis syndrome.

Hepatocardiorenal syndrome in liver cirrhosis:Recognition of a new entity?

Emerging evidence and perspectives have pointed towards the heart playing an important role in hepatorenal syndrome(HRS),outside of conventional understanding that liver cirrhosis is traditionally considered the sole origin of a cascade of pathophysiological mechanisms directly affecting the kidneys in this context.In the absence of established heart disease,cirrhotic cardiomyopathy may occur more frequently in those with liver cirrhosis and kidney disease.It is a specific form of cardiac dysfunction characterized by blunted contractile responsiveness to stress stimuli and altered diastolic relaxation with electrophysiological abnormalities.Despite the clinical description of these potential cardiac-related complications of the liver,the role of the heart has traditionally been an overlooked aspect of circulatory dysfunction in HRS.Yet from a physiological sense,temporality(prior onset)of cardiorenal interactions in HRS and positive effects stemming from portosystemic shunting demonstrated an important role of the heart in the development and progression of kidney dysfunction in cirrhotic patients.In this review,we discuss current concepts surrounding how the heart may influence the development and progression of HRS,and the role of systemic inflammation and endothelial dysfunction causing circulatory dysfunction within this setting.The temporality of heart and kidney dysfunction in HRS will be discussed.For a subgroup of patients who receive portosystemic shunting,the dynamics of cardiorenal interactions following treatment is reviewed.Continued research to determine the unknowns in this topic is anticipated,hopefully to further clarify the intricacies surrounding the liver-heart-kidney connection and improve strategies for management.