Mitral valvuloplasty using real-time three-dimensional transesophageal echocardiography.

OBJECTIVE: This study aimed to investigate the structure of the mitral valve in patients undergoing mitral valvuloplasty (MVP) using real-time three-dimensional transesophageal echocardiography (RT-3D-TEE). The main objective was to study the relationship between intraoperative annuloplasty ring size and mitral valve structure dimensions, with a focus on exploring the application value of RT-3D-TEE in MVP. METHODS: A total of 28 patients with degenerative mitral regurgitation (DMR), who underwent MVP between February and September 2022, as well as 12 normal control cases, were enrolled in this study. The MV annulus and leaflets were quantitatively analyzed using MVN software. RESULTS: The DMR group exhibited significantly greater dimensions in various parameters of the mitral valve, including the anterolateral-to-posteromedial diameter (DAlPm ), anterior-to-posterior diameter (DAP ), annulus height (HA ), three-dimensional annulus circumference (CA3D ), two-dimensional annulus area (AA2D ), anterior leaflet area (Aant ), posterior leaflet area (Apost ), anterior leaflet length (Lant ), posterior leaflet length (Lpost ), and tenting volume (Vtent ) compared to the control group. CONCLUSION: Real-time three-dimensional transesophageal echocardiography provides valuable insights into the morphological structure of the mitral valve and lesion location. It can aid in surgical decision-making, validate the success of MVP, and potentially reduce mortality and complications associated with mitral valve repair procedures.

Minimally Invasive Direct Coronary Artery Bypass Versus Percutaneous Coronary Intervention for Isolated Left Anterior Descending Artery Stenosis: An Updated Meta-Analysis.

BACKGROUND: The optimal revascularization strategy for isolated left anterior descending (LAD) coronary artery lesion between minimally invasive direct coronary artery bypass (MIDCAB) and percutaneous coronary intervention (PCI) remains controversial. This updated meta-analysis aims to compare the long- and short-term outcomes of MIDCAB versus PCI for patients with isolated LAD coronary artery lesions. METHODS: The Pubmed, Web of Science, and Cochrane databases were searched for retrieving potential publications from 2002 to 2022. The primary outcome was long-term survival. Secondary outcomes were long-term target vessel revascularization (TVR), long-term major adverse cardiovascular events (MACEs), and short-term outcomes, including postoperative mortality, myocardial infarction (MI), TVR, and MACEs of any cause in-hospital or 30 days after the revascularization. RESULTS: Six randomized controlled trials (RCTs) and eight observational studies were included in this updated meta-analysis. In total, 1757 patients underwent MIDCAB and 15245 patients underwent PCI. No statistically significant difference was found between the two groups in the rates of long-term survival. MIDCAB had a lower long-term MACE rate compared with PCI. Besides, PCI resulted in an augmented risk of TVR. Postoperative mortality, MI, TVR, and MACEs were similar between the two groups. CONCLUSIONS: The updated meta-analysis presents the evidence that MIDCAB has a reduced risk of long-term TVR and MACEs, with no benefit in terms of long-term mortality and short-term results, in comparison with PCI. Large multicenter RCTs, including patients treated with newer techniques, are warranted in the future.

Lymphocyte-to-monocyte ratio associated with severe post-stenotic aortic dilation in a case-control study.

BACKGROUND: Calcific aortic valve stenosis (CAVS) represents a serious health threat to elderly patients. Post-stenotic aortic dilation, a common feature in CAVS patients, might progress into aneurysm and even dissection, potential consequences of CAVS, and predicts a poor prognosis. This study sought to investigate the association of lymphocyte-to-monocyte ratio (LMR), an inflammatory biomarker, with severe post-stenotic aortic dilation in a case-control study in Chinese population. MATERIALS AND METHODS: 208 consecutive patients with CAVS were recruited retrospectively in a case-control study in Chinese population, from July 1, 2015 to June 31, 2018. LMR was statistically analyzed using the ROC curve and binary logistic regression analyses for its prognostic value in severe post-stenotic aortic dilation. RESULTS: LMR was significantly reduced in patients with severe post-stenotic aortic dilation (2.72 vs. 3.53, p = 0.002 < 0.05) compared to patients without severe post-stenotic aortic dilation. There was an inverse correlation observed between the maximal diameter of ascending aorta and LMR in the overall patients (r = - 0.217, p = 0.002 < 0.05). For post-stenotic aortic dilation, the prevalence of high-LMR group was statistically lower than that of low-LMR group (19.7% vs. 43.9%, p < 0.001). The maximal diameter of ascending aorta was significantly reduced in the high-LMR group (4.35 vs. 4.76, p = 0.003 < 0.05) compared to low-LMR group. Additionally, LMR was identified in the multivariate analysis independently associated with severe post-stenotic aortic dilation (AUC 0.743, 95% CI: [0.573-0.964], p = 0.025). CONCLUSIONS: This study provided the evidence of an inverse correlation between severe post-stenotic aortic dilation and LMR. LMR is potentially independently associated with severe post-stenotic aortic dilation.

Association of serum anion gap and risk of long-term mortality in patients following coronary artery bypass grafting: A propensity score matching study.

BACKGROUND: The present study aimed to explore the relationship between serum anion gap (AG) and long-term mortality in patients undergoing coronary artery bypass grafting (CABG). METHODS: Clinical variables were extracted among patients undergoing CABG from Medical Information Mart for Intensive Care III (MIMIC III) database. The primary outcome was 4-year mortality following CABG. An optimal cut-off value of AG was determined by the receiver operating characteristic (ROC) curve. The Kaplan-Meier (K-M) analysis and multivariate Cox hazard analysis were performed to investigate the prognostic value of AG in long-term mortality after CABG. To eliminate the bias between different groups, propensity score matching (PSM) was conducted to validate the findings. RESULTS: The optimal cut-off value of AG was 17.00 mmol/L. Then a total of 3162 eligible patients enrolled in this study were divided into a high AG group (≥17.00, n = 1022) and a low AG group (<17.00, n = 2,140). A lower survival rate was identified in the high AG group based on the K-M curve (p < .001). Compared with patients in the low AG group, patients in the high AG group had an increased risk of long-term mortality [1-year mortality: hazard ratio, HR: 2.309, 95% CI (1.672-3.187), p < .001; 2-year mortality: HR: 1.813, 95% CI (1.401-2.346), p < .001; 3- year mortality: HR: 1.667, 95% CI (1.341-2.097), p < .001; 4-year mortality: HR: 1.710, 95% CI (1.401-2.087), p < .001] according to multivariate Cox hazard analysis. And further validation of above results was consistent in the matched cohort after PSM. CONCLUSIONS: The AG is an independent predictive factor for long-term all-cause mortality in patients following CABG, where a high AG value is associated with an increased mortality.

Percardiac closure of large apical ventricular septal defects in infants: Novel modifications and mid-term results.

BACKGROUND/AIM: Both open heart surgery and percutaneous approaches retain several limitations in closing large apical muscular ventricular septal defects (AmVSD) in infants. We present probe-assisted percardiac device closure (PDC), an exclusively transoesophageal-echocardiography guided technique, as an alternative with midterm results. METHODS: Thirty-six infants with large AmVSDs (single or multiple-holed) underwent PDC in our department. Mean AmVSD for single and multiple-holed measured 7.2 ± 2.4 mm and 6.3 ± 3.4 mm, respectively. Subjects presented with a spectrum of cardiopulmonary sequelae and growth retardation, either alone or combined. Some were ventilator dependent and re-do cases. In addition, AmVSDs were categorized: cylindrical, tunnel and cave-like shaped as per color Doppler interrogation. Pursuant to cardiac access and deployment technique, subjects were apportioned: group A; inferior median sternotomy (perventricular), B; right mini-thoracotomy (peratrial) and C; complete median sternotomy (perventricular). Under exclusive echocardiography, the Z- or J probe-assisted delivery system was utilized to access AmVSDs and implant device(s) via aforementioned techniques. RESULTS: Forty-two muscular ventricular septal devices (8.4 ± 2.6 mm) were implanted in 36 subjects uneventfully. Seventeen "complex," and 10 cylindrical or straight tunnel-shapedAmVSDs (including 2 re-do patients) suited perventricular and peratrial techniques respectively. Comparatively, group B exhibited shorter procedural indices than A (p < .01). Five of 15 multiple-holed AmVSDs (four Swiss cheese) required two or three devices for a satisfactory occlusion. Nevertheless, post occlusion insignificant residual shunts( ≤ 2 mm) seldom achieved spontaneous closure, and at 36-month follow-up complete closure was 67%. Residual shunt persisted amongst multiple-holed. All patients improved during follow up. CONCLUSION: PDC is feasible, safe and effective alternative technique for AmVSD in infants.

Traumatic mitral annular avulsion and interventricular septum dissection.

We presented a rare case of traumatic mitral annular avulsion and interventricular septum dissection after an unintentional falling injury in a 5-year-old female child. A successful surgical repair of mitral annulus and interventricular septum was performed to restore the haemodynamic stability.

Expression of pulmonary arterial elastin in rats with hypoxic pulmonary hypertension using H2S.

Object: This study analyses the changes of pulmonary arterial elastin expression inhibited by hydrogen sulfide (H2S) in rats with hypoxic pulmonary hypertension.Method: The research used 30 healthy rats and randomly divided them into control group, hypoxia group, and hypoxia + sodium hydrosulfide group. Each group contains 10 samples. The right catheterization was selected to measure the mean pulmonary artery pressure (mPAP). The RV/LV + S ratio was calculated through separating the right ventricle and the left ventricle plus the interventricular septum. Optical microscopy was used to observe the changes of pulmonary vascular structure. The research used immunohistochemistry to express the levels of elastin and transforming growth factor beta (TGF-ß).Results: The ratios of Mpap and RV/LV + S in the hypoxic group exceed the control group. The hypoxia + sodium hydrosulfide group (hypoxia + NaHS) is lower than the hypoxic group. In the hypoxic group, the elastic expressions of medium and small pulmonary artery smooth muscle cells exceed the control group. The expression of elastin in hypoxic + NaHS medium and small pulmonary artery smooth muscle cells is lower than that of the control group.The protein expression levels of α-SM-actin in muscle arterial smooth muscle of pulmonary arterioles in hypoxic group, control group and hypoxic + NaHS group were 49.84% + 6.27%, 56.84% + 6.38%, 23.82% + 3.84%, 27.51% + 3.24%, 29.00% + 4.05%, 34.72% + 3.38%.Conclusion: Hydrogen sulfide in rats with hypoxic pulmonary hypertension can inhibit the expression of elastin in its extracellular matrix, which also has remarkable regulation function in forming HPH and remodeling hypoxic pulmonary vascular structure.

Progress in the seasonal variations of blood lipids: a mini-review.

The seasonal variations of blood lipids have recently gained increasing interest in this field of lipid metabolism. Elucidating the seasonal patterns of blood lipids is particularly helpful for the prevention and treatment of cardiovascular and cerebrovascular diseases. However, the previous results remain controversial and the underlying mechanisms are still unclear. This mini-review is focused on summarizing the literature relevant to the seasonal variability of blood lipid parameters, as well as on discussing its significance in clinical diagnoses and management decisions.

Endothelial-to-Mesenchymal Transition in Calcific Aortic Valve Disease.

Calcific aortic valve disease (CAVD) represents a significant threat to cardiovascular health worldwide, and the incidence of this sclerocalcific valve disease has rapidly increased along with a rise in life expectancy. Compelling evidence has suggested that CAVD is an actively and finely regulated pathophysiological process even though it has been referred to as "degenerative" for decades. A striking similarity has been noted in the etiopathogenesis between CAVD and atherosclerosis, a classical proliferative sclerotic vascular disease.1 Nevertheless, pharmaceutical trials that attempted to target inflammation and dyslipidemia have produced disappointing results in CAVD. While senescence is a well-documented risk factor, the sophisticated regulatory networks have not been adequately explored underlying the aberrant calcification and osteogenesis in CAVD. Valvular endothelial cells (VECs), a type of resident effector cells in aortic leaflets, are crucial in maintaining valvular integrity and homeostasis, and dysfunctional VECs are a major contributor to disease initiation and progression. Accumulating evidence suggests that VECs undergo a phenotypic and functional transition to mesenchymal or fibroblast-like cells in CAVD, a process known as the endothelial-to-mesenchymal transition (EndMT) process. The relevance of this transition in CAVD has recently drawn great interest due to its importance in both valve genesis at an embryonic stage and CAVD development at an adult stage. Hence EndMT might be a valuable diagnostic and therapeutic target for disease prevention and treatment. This mini-review summarized the relevant literature that delineates the EndMT process and the underlying regulatory networks involved in CAVD.

Yap overexpression attenuates septic cardiomyopathy by inhibiting DRP1-related mitochondrial fission and activating the ERK signaling pathway.

Context: Yes-associated protein (Yap) has been linked to several cardiovascular disorders, but the role of this protein in septic cardiomyocytes is not fully understood. Objective: The aim of our study was to explore the influence of Yap in septic cardiomyopathy in vivo and in vitro. Materials and methods: In the current study, Yap transgenic mice and Yap adenovirus-mediated gain-of-function assays were used in an LPS-established septic cardiomyopathy model. Mitochondrial function and mitochondrial fission were determined through western blotting, immunofluorescence analysis and ELISA. Results: Our results demonstrated that Yap expression was downregulated by LPS, whereas Yap overexpression sustained cardiac function and attenuated cardiomyocyte death. The functional exploration revealed that LPS treatment induced cardiomyocyte mitochondrial stress, as manifested by mitochondrial superoxide overproduction, cardiomyocyte ATP deprivation, and caspase-9 apoptosis activation. Furthermore, we demonstrated that LPS-mediated mitochondrial damage was controlled by mitochondrial fission. However, Yap overexpression reduced mitochondrial fission and therefore improved mitochondrial function. A molecular investigation revealed that Yap overexpression inhibited mitochondrial fission by reversing ERK activity, and the inhibition of the ERK pathway promoted DRP1 upregulation and thereby mediated mitochondrial fission activation in the presence of Yap overexpression. Conclusions: Overall, our results suggest that the cause of septic cardiomyopathy appears to be connected with Yap downregulation. The overexpression of Yap can attenuate myocardial inflammation injury through the reduction of DRP1-related mitochondrial fission in an ERK pathway activation-dependent manner.

Functional SNP in the 3'UTR of PON1 is Associated with the Risk of Calcific Aortic Valve Stenosis via MiR-616.

BACKGROUND/AIMS: Previous studies have examined the associations between the single nucleotide polymorphism in the Paraoxonase 1 (PON1) gene and development of calcific aortic valve stenosis (CAVS). The association between functional SNP in 3'UTR of PON1 and the risk of CAVS, however, is unclear. In this study, we investigated the role of SNP in the regulation of PON1 expression via miR-616, as well as the association of SNP with the risk of CAVS. METHODS: Two hundred and sixteen patients with CAVS and 243 CAVS-free participants were recruited in this study.They all obtained transthoracic echocardiogram and the ejection fraction (EF) and aortic valve area were recorded and analyzed. The PON1 expression were measured by western blot, Quantitative Real-Time Polymerase Chain Reaction were used to examine the transcriptional activity of miR-616 and PON1. Differences between CVAS patients and controls in terms of genotype frequency distribution and the estimates of Hardy-Weinberg equilibrium were evaluated using chi-square tests. Logistic regression modeling was used to determine the association between the independent effect of rs3735590 SNP and the interaction between genotype, PON1 activity, and other covariates on lipids and CAVS risk. All statistical analyses were performed using SPSS, version 17.0.1 for Windows (SPSS Inc., Chicago, IL). A p value of < 0 .05 was considered significant for all analyses. RESULTS: This study confirmed that PON1 is a validated target gene of miR-616 in liver cells. The relative quantification representing the expression of PON1 mRNA and the serum level of PON1 protein was decreased in the TT genotype. Moreover, the expression of PON1 had a negative regulatory relationship with the expression of miR-616(r=-0.3959, P<0.05) in human tissues. The patients with CT OR TT genotype at loci rs3735590 had a lower risk of CAVS than patients with the CC genotype. CONCLUSIONS: Our results suggest that functional SNP in the 3'UTR of PON1 regulates the expression of PON1 via miR-616, and such SNP is associated with the risk of CAVS in human.

Peratrial Device Closure of a Congenital Coronary Artery Fistula through a Right Parasternal Approach: Innovative Use of Available Technology.

Current treatments for congenital coronary artery fistulas (CAFs) include surgical obliteration and transcatheter occlusion. However, surgical techniques involve significant trauma. Transcatheter occlusion is performed under fluoroscopy and angiography, in which radiation injury is inevitable. We present a patient, with a CAF from the left coronary artery to the right atrium, who underwent peratrial device closure of the CAF with a right parasternal approach under transesophageal echocardiography guidance. Complete occlusion was achieved by a symmetric ventricular septal occluder. We suggest that peratrial device closure of a congenital coronary artery fistula through a right parasternal approach may be a safe and effective option.

MAP4K4 deletion inhibits proliferation and activation of CD4(+) T cell and promotes T regulatory cell generation in vitro.

CD4(+) T cells are critical for adaptive immunity. MAP4K4 is a key member of germinal center kinase group. However, the physiological function of MAP4K4 in primary CD4(+) T cells is still unclear. In this study, it was demonstrated that in vitro, MAP4K4 deletion remarkably suppressed CD4(+) T cell proliferation in response to phorbol 12-myristate 13-acetate (PMA) and ionomycin, which was not due to enhancing cell apoptosis. Additionally, MAP4K4 was required for the activation of CD4(+) T cells. MAP4K4 deletion significantly down-regulated expression of interleukin 2 (IL-2) and interferon-γ (IFN-γ), while notably up-regulating the expression of regulatory T cells (Treg) transcription factor Foxp3 in peripheral CD4(+) T cells. Furthermore, western blot analysis indicated that CD4(+) T cells lacking MAP4K4 failed to phosphorylate Jnk, Erk, p38 and PKC-θ. Thus, our results provide the evidence that MAP4K4 is essential for CD4(+) T cell proliferation, activation and cytokine production.

Significance of dynamic changes in the fragmented QRS complex in acute pulmonary embolism.

BACKGROUND: Dynamic changes in the fQRS complex between the initial and follow-up ECG in patients with acute pulmonary embolism (APE) have rarely been studied. OBJECTIVE: The purpose of this study was to investigate the significance of dynamic changes in the fragmented QRS complex in APE patients. METHODS: APE patients (n = 222) were divided into three groups based on their ECG data to determine whether there were dynamic changes in the fQRS complex from admission to follow-up at one month: the fQRS shallower group (n = 49), fQRS deeper group (n = 25) and fQRS unchanged group (n = 148). Each patient was observed and followed for 12 months. RESULTS: Cox multivariate logistic regression analysis indicated that the dynamic deeper fQRS complex was an independent predictor of long-term mortality (HR: 5.563, 95 % CI: 1.079-28.678, P = 0.040) in patients with APE. Kaplan-Meier curve analysis revealed that the event-free survival of the fQRS shallower group significantly increased relative to that of the fQRS deeper group and that of the fQRS deeper group significantly decreased relative to that of the fQRS unchanged group and shallower group (P = 0.022, P = 0.041). CONCLUSION: Compared with the deeper fQRS complex, the dynamic shallower fQRS complex was an indicator of a good prognosis in APE patients, while the dynamic deeper fQRS complex indicated a poor prognosis. Dynamical changes in fQRS may assist clinicians in risk stratification and individualized treatment for APE, as well as in predicting APE regression or progression.

Evaluation of Left Ventricular Function in Patients With Severe Aortic Stenosis Utilizing Automated Cardiac Motion Quantitation Techniques.

OBJECTIVE: The objective of this study is to explore the patterns of alteration in left ventricular systolic function among patients with severe aortic stenosis (SAS) through the application of automatic myocardial motion quantification (aCMQ) techniques. Furthermore, we seek to ascertain dependable quantitative markers for the assessment of impaired left ventricular function in patients with SAS and an ejection fraction (EF) ≥ 60%. METHODS: Seventy patients who underwent echocardiography and received a diagnosis of severe aortic stenosis (SAS) in the hospital from November 2021 to August 2022 were selected for the SAS group and categorized into three subgroups based on ejection fraction (EF)-SAS group with EF ≥ 60%, SAS group with EF ranging from 50% to 59%, and SAS group with EF < 50%. Concurrently, 30 healthy individuals were recruited at the hospital during the same timeframe to serve as the control group. Participants from both groups underwent standard transthoracic echocardiography to assess conventional echocardiographic parameters. Dynamic images were examined using automatic myocardial motion quantification (aCMQ) software to derive longitudinal peak strain (LPS) parameters, which were then subjected to statistical analysis. RESULTS: In comparison to the control group participants, the measurements of ascending aorta diameter (AoD), left atrium diameter (LAD), interventricular septal end diastolic thickness (IVSd), left ventricular posterior wall end diastolic thickness (LVPWd), peak systolic velocity (Vmax), and mean pressure gradient (MPG) were significantly higher in the SAS groups (p < 0.05). When compared to participants in the SAS group with an EF ≥ 60%, the values of IVSd, LVPWd, Vmax, and MPG in the SAS group with EF ranging from 50% to 59% were significantly elevated (p < 0.05). Similarly, left ventricular end-diastolic diameter (LVEDD), the ratio of early diastolic mitral inflow velocity to early diastolic mitral annular velocity (E/e'), and the ratio of early to late diastolic mitral inflow velocities (E/A) in the SAS group with EF < 50% were significantly elevated (p < 0.05). The absolute values of longitudinal peak strain (LPS) in the SAS groups were significantly lower in comparison to those in the control group (p < 0.05). Furthermore, all measurements of left ventricular global longitudinal systolic peak strain (GLPS) showed a positive correlation with MPG, a moderate negative correlation with aortic valve area index (AVAI), and a moderate positive correlation with E/A. CONCLUSIONS: Patients with SAS and an EF < 50% exhibited the most profound impairment in left ventricular myocardial function. Utilizing the aCMQ technique enables the precise and quantitative evaluation of the severity of impaired left ventricular systolic function in patients within the SAS group with an EF ≥ 60%.

CaAOS as a hub gene based on physiological and transcriptomic analyses of cold-resistant and cold-sensitive pepper cultivars.

The yield and quality of pepper are considerably influenced by the cold conditions. Herein, we performed morphological, physiological and transcriptomic analyses by using two pepper seedlings, '2379' (cold-resistant) and '2380' (cold-sensitive). Briefly, 60 samples from each cultivar were analyzed at four distinct time points (0, 6, 24 and 48 h) at 5 °C in darkness. The physiological indices and activities of enzymes exhibited marked differences between the two cultivars. Transcriptomic analysis indicated that, compared to the control group, 11,415 DEGs were identified in '2379' and '2380' at 24 h. In the early stage, the number of DEGs in '2379' was 5.68 times higher than that in '2380', potentially explaining the observed differences in tolerance to colds. Processes such as protein targeting to membranes, jasmonic acid (JA)-mediated signalling, cold response and abscisic acid-activated signalling were involved. Subsequently, we identified a hub gene, CaAOS, that is involved in JA biosynthesis, positively influences cold tolerance and is a target of CaMYC2. Variations in the GC-motif of the CaAOS's promoter may influence the expression levels of CaAOS under cold treatment. The result of this study may lead to the development of more effective strategies for enhancing cold tolerance, potentially benefitting pepper breeding in cold regions.

Coronary pseudoaneurysm with a superficial mass and accompanying Brucella infection.

BACKGROUND AND AIMS: To our knowledge, no previously reported clinical data of a coronary artery fistula forming a pseudoaneurysm and presenting as a anterior chest wall lump. We reported a rare case of Coronary pseudoaneurysm with a superficial mass and accompanying Brucella infection. The patient was successfully treated with surgery. MATERIALS AND METHODS: The patient case data was extracted from hospital records. RESULTS: A 64-year-old male presented with a history of paroxysmal left-sided chest pain and painful anterior chest wall lump. Coronary computed tomography (CT) angiography revealed the RCA pseudoaneurysm that showed a peripherally calcified soft-tissue mass in the anterior mediastinum and communicated with the chest wall lump through intercostal spaces. The patient underwent the resection of chest lump and RCA pseudoaneurysm under cardiopulmonary bypass, along with a combined antimicrobial therapy. The patient was discharged successfully after the surgery. DISCUSSION AND CONCLUSION: We report this rare case and highlight the possible origin of the anterior mediastinal mass and anterior chest wall lump as a pseudoaneurysm formed by a coronary artery fistula.

Stochastic contribution for the coding of agonist induced calcium oscillation in hepatocytes.

The influence of stochastic inositol-1,4,5-trisphosphate receptor (IP3R) dynamics and their clustering have been extensively investigated to explore the mechanism through which the stochastic molecular event finally shape the intracellular calcium signaling. Most of the previous works employed simplified models which take the concentration of IP3 instead of that of the agonist as the stimulation intensity. However, the IP3 level is not linearly dependent on the agonist concentration in stimulus induced signaling systems because there are feedback links in the transduction network. In this work, we include both the IP3R dynamics and the typical agonist induced signaling transduction cascade in the model to investigate the essential influence of stochastic IP3R dynamics on the coding of the stimulus induced calcium signal. Simulation results reveal two distinct oscillation areas under different stimulation levels. The signal is optimally modulate by the IP3R cluster number in the weak stimulated area while affected by the stimulus intensity in the strong stimulated area. Different dependences of coefficient of variance (CV) on the number of clusters are obtained in these two areas, which explains the disagreement in the previous reported results. Besides, the transition between these areas explains the significant CV reduction observed in experiments.

Body mass index-associated responses to an ABVD-like regimen in newly-diagnosed patients with Hodgkin lymphoma.

Background: The role of body mass index (BMI) in the treatment outcomes of lymphoma patients is controversial. While investigating the efficacy of ABVD-like regimen in Hodgkin lymphoma (HL) patients, we observed that obese patients had poor responses. To better understand this clinical phenomenon, we evaluated the effect of BMI on responses to ABVD-like chemotherapy in HL patients. Methods: This retrospective cohort study evaluated the clinical outcomes of all 67 patients with confirmed HL who were treated at the First Affiliated Hospital of Soochow University from November 2016 to March 2023 with an ABVD-like regimen as first-line chemotherapy. Baseline patient characteristics and clinical outcomes were compared across different BMI categories. The primary end-point was the overall response rate defined as the proportion of the HL patients who achieved complete response or partial response. The additional end-points included progression-free survival and overall survival. Results: The median age of the HL patients was 31 years old. Of the patients, 10.4% were obese, and 17.9% patients were overweight. Interim and end-term response evaluations revealed overall response rates of 98.5% and 83.6%, respectively. The proportion of patients with potential poor prognostic factors (IPS risk factors) did not differ significantly in the responders versus non-responders. However, non-responders had a higher average BMI when compared with responders (p = 0.002). Poor overall response rates in higher BMI patients indeed manifested with shorter progression free survival (p = 0.013). The minimum relative dose of the ABVD-like regimen in the overweight and obese groups was significantly lower than in the normal weight group (p < 0.001). Conclusion: Our analyses show that >80% of newly-diagnosed HL patients responded to the ABVD-like regimen. We find that being obese or overweight at the time of diagnosis correlated with a poorer overall response rate and that BMI was an independent risk factor in HL patients treated with the ABVD-like regimen. Lower doses of ABVD-like regimen contributed to the discrepant findings of responses in the high BMI groups. These findings indicate that newly-diagnosed, obese HL patients receiving an ABVD-like regimen require personalized treatment.