Downregulation of stromal interaction molecule-1 is implicated in the age-associated vasoconstriction dysfunction of aorta, intrarenal, and coronary arteries.

The contractile function of vascular smooth muscle cells (VSMCs) typically undergoes significant changes with advancing age, leading to severe vascular aging-related diseases. The precise role and mechanism of stromal interaction molecule-1 (STIM1) in age-mediated Ca2+ signaling and vasocontraction remain unclear. The connection between STIM1 and age-related vascular dysfunction was investigated using a multi-myograph system, immunohistochemical analysis, protein blotting, and SA-ß-gal staining. Results showed that vasoconstrictor responses in the thoracic aorta, intrarenal artery, and coronary artery decreased with age. STIM1 knockdown in the intrarenal and coronary arteries reduced vascular tone in young mice, while no change was observed in the thoracic aorta. A significant reduction in vascular tone occurred in the STIM1 knockout group with nifedipine. In the thoracic aorta, vasoconstriction significantly decreased with age following the use of nifedipine and thapsigargin and almost disappeared after STIM1 knockdown. The proportion of senescent VSMCs increased significantly in aged mice and further increased in sm-STIM1 KO aged mice. Moreover, the expression of senescence markers p21, p16, and IL-6 significantly increased with age, with p21 expression further increased in the STIM1 knockdown aged group, but not p16 or IL-6. These findings indicate that different arteries exhibit distinct organ-specific features and that STIM1 downregulation may contribute to age-related vasoconstrictive dysfunction through activation of the p21 pathway.

Risk factors analysis and the establishment of nomogram prediction model for PICC-related venous thrombosis in patients with lymphoma: a double-center cohort-based case-control study.

Objective: The objective of this study is to examine the risk factors associated with the occurrence of PICC-Related Venous Thrombosis (PICC-RVTE) in individuals diagnosed with lymphoma, as well as to develop a predictive risk nomogram model. Methods: A total of 215 patients with lymphoma treated at Yunnan Provincial Tumor Hospital from January 2017 to December 2020 were retrospectively evaluated as the training cohort; 90 patients with lymphoma treated at the Department of Oncology of the First People's Hospital of Anning, Affiliated to Kunming University of Science and Technology during the January 2021 to September 2023 were evaluated as the validation cohort. Independent influencing factors were analyzed by logistic regression, a nomogram was developed and validated, and the model was evaluated using internal and external data cohorts for validation. Results: A total of 305 lymphoma patients were selected and 35 (11.48%) PICC-RVTE occurred, the median time was 13 days. The incidence within 1-2week was 65.71%. Multivariate analysis suggested that the activity amount, thrombosis history(within the last 12 months), ATIII, Total cholesterol and D-dimer levels were independently associated with PICC-RVTE, and a nomogram was constructed based on the multivariate analysis. ROC analysis indicated good discrimination in the training set (area under the curve [AUC] = 0.907, 95%CI:0.850-0.964) and the testing set (AUC = 0.896, 95%CI: 0.782-1.000) for the PICC-RVTE nomogram. The calibration curves showed good calibration abilities, and the decision curves indicated the clinical usefulness of the prediction nomograms. Conclusions: Patients should be advised to undergo color Doppler ultrasound system testing within two week after the implantation of a PICC catheter to detect PICC-RVTE at an early stage. The validated nomogram can be used to predict the risk of catheter-related thrombosis (CRT) in patients with lymphoma who received at least one chemotherapy after PICC catheterization, no bleeding tendency, no recent history of anticoagulant exposure and no severe heart, lung, renal insufficiency. This model has the potential to assist clinicians in formulating individualized treatment strategies for each patient.

Clinical Characteristics and Outcomes of Chinese Patients with Premature Acute Coronary Syndrome.

This study aimed to investigate the clinical characteristics and major adverse cardiovascular events (MACEs) of Chinese patients with premature acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). This study was a secondary retrospective analysis involving 2114 ACS patients undergoing PCI at a single center in China. The patients were divided into two groups according to age (premature ACS group: ≤ 55 years in men, ≤ 65 years in women; nonpremature ACS group: > 55 years in men, > 65 years in women). The primary endpoint was all-cause death, and the secondary endpoint was a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, target vessel revascularization, and recurrent angina at follow-up, defined as MACEs. The incidence of all-cause death and MACEs was significantly lower in the premature than in the nonpremature ACS group (P < 0.001). Female sex, higher triglyceride levels, and higher low-density lipoprotein cholesterol levels were identified as independent risk factors that accelerated the development of ACS, whereas higher high-density lipoprotein cholesterol levels were identified as protective factors. Furthermore, in patients with premature ACS, non-ST-elevation ACS, cardiac insufficiency, multivessel disease, and left main lesion were risk factors for MACEs. Younger individuals, especially females, are advised to undergo early screening for the risk factors of premature ACS. Primary prevention of dyslipidemia should be more aggressively promoted at a young age. For premature ACS patients undergoing PCI, strengthened management and regular re-examinations are necessary to avoid adverse cardiovascular events as much as possible.

Sophocarpine Alleviates Isoproterenol-Induced Kidney Injury by Suppressing Inflammation, Apoptosis, Oxidative Stress and Fibrosis.

One of the most common diseases affecting people and leading to high morbidity is kidney injury. The alleviation of inflammation and apoptosis is considered a potential therapeutic approach for kidney injury. Sophocarpine (SOP), a tetracyclic quinolizidine alkaloid, exhibits various beneficial biological properties. To investigate the effects of SOP on isoproterenol (ISO)-induced kidney injury, we randomly divided mice into four groups: Control, ISO, ISO+SOP (20 mg/kg) and ISO+SOP (40 mg/kg). SOP was administered intraperitoneally to the mice over two weeks, accompanied by intraperitoneal stimulation of ISO (10 mg/kg) for another four weeks. After the mice were sacrificed, several methods such as ELISA, staining (H&E, TUNEL, DHE and Masson) and Western blotting were applied to detect the corresponding indicators. The kidney injury serum biomarkers SCr and BUN increased after the ISO challenge, while this effect was reversed by treatment with SOP. Pathological changes induced by ISO were also reversed by treatment with SOP in the staining. The inflammatory cytokines IL-ß, IL-6, TNF-α, MCP-1 and NLRP3 increased after the challenge with ISO, while they were decreased by treatment with SOP. The apoptotic proteins cleaved-caspase-3 and Bax increased, while Bcl-2 decreased, after the challenge with ISO, and these effects were reversed by treatment with SOP. The antioxidant proteins SOD-1 and SOD-2 decreased after being stimulated by ISO, while they increased after the treatment with SOP. The fibrotic proteins collagen I, collagen III, α-SMA, fibronectin, MMP-2 and MMP-9 increased after the challenge with ISO, while they decreased after the treatment with SOP. We further discovered that the TLR-4/NF-κB and TGF-ß1/Smad3 signaling pathways were suppressed, while the Nrf2/HO-1 signaling pathway was activated. In summary, SOP could alleviate ISO-induced kidney injury by inhibiting inflammation, apoptosis, oxidative stress and fibrosis. The molecular mechanisms were suppression of the TLR-4/NF-κB and TGF-ß1/Smad3 signaling pathways and activation of the Nrf2/HO-1 signaling pathway, indicating that SOP might serve as a novel therapeutic strategy for kidney injury.

The changes of the peripheral CD4+ lymphocytes and inflammatory cytokines in Patients with COVID-19.

To investigate the clinical value of changes in the subtypes of peripheral blood lymphocytes and levels of inflammatory cytokines in patients with COVID-19, the total numbers of lymphocytes and CD4+ lymphocytes and the ratio of CD4+/CD8+ lymphocytes were calculated and observed in different groups of patients with COVID-19. The results show that the lymphocytopenia in patients with COVID-19 was mainly manifested by decreases in the CD4+ T lymphocyte number and the CD4+/CD8+ ratio. The decreased number of CD4+ T lymphocytes and the elevated levels of TNF-α and IL-6 were correlated with the severity of COVID-19 disease.

Valuation of Normal Range of Ankle Systolic Blood Pressure in Subjects with Normal Arm Systolic Blood Pressure.

SUBJECT: This study aimed to establish a normal range for ankle systolic blood pressure (SBP). METHODS: A total of 948 subjects who had normal brachial SBP (90-139 mmHg) at investigation were enrolled. Supine BP of four limbs was simultaneously measured using four automatic BP measurement devices. The ankle-arm difference (An-a) on SBP of both sides was calculated. Two methods were used for establishing normal range of ankle SBP: the 99% method was decided on the 99% reference range of actual ankle BP, and the An-a method was the sum of An-a and the low or up limits of normal arm SBP (90-139 mmHg). RESULTS: Whether in the right or left side, the ankle SBP was significantly higher than the arm SBP (right: 137.1 ± 16.9 vs 119.7 ± 11.4 mmHg, P<0.05). Based on the 99% method, the normal range of ankle SBP was 94~181 mmHg for the total population, 84~166 mmHg for the young (18-44 y), 107~176 mmHg for the middle-aged(45-59 y) and 113~179 mmHg for the elderly (≥ 60 y) group. As the An-a on SBP was 13 mmHg in the young group and 20 mmHg in both middle-aged and elderly groups, the normal range of ankle SBP on the An-a method was 103-153 mmHg for young and 110-160 mmHg for middle-elderly subjects. CONCLUSION: A primary reference for normal ankle SBP was suggested as 100-165 mmHg in the young and 110-170 mmHg in the middle-elderly subjects.

Meta-analysis of coronary artery bypass graft surgery combined with stem cell transplantation in the treatment of ischemic heart diseases.

OBJECTIVE: The use of bone marrow cells (BMCs) to regenerate the myocardium and vessels is a new treatment for ischemic heart diseases (IHD) that has been receiving attention. In this study, a meta-analysis was used to analyze the efficacy of combining coronary artery bypass graft (CABG) surgery with BMC transplantation in the treatment of IHD. METHODS AND RESULTS: MEDLINE, EMBASE, Cochrane, CNKI, WAN-FANG, and WEI-PU databases were searched. The main inclusion criteria were as follows: (a) studies that analyzed patients diagnosed with chronic IHD. (b) Studies that had randomized-controlled trials. (c) Studies that included research comparing the efficacy of CABG and CABG combined with bone BMC transplantation in the treatment of IHD. (d) Studies with specific enumeration data at the end of the follow-up with a follow-up time of at least 3 months. Nine randomized trials were included. There were 158 patients in the group that received the treatment of CABG surgery as well as stem cell transplantation, referred to as the 'cell transplantation group.' A total of 147 patients were in the group that only received the treatment of CABG surgery, referred to as the 'CABG group'. Our data show that not only did stem cell transplantation significantly improve left ventricular ejection fraction (odds ratio=11.7, 95% confidence interval: 4.04-19.36; P=0.003) but it also significantly reduced the left ventricular end-diastolic volume and left ventricular end-systolic volume (P<0.001). CONCLUSION: BMC transplantation is associated with a significant improvement in left ventricular ejection fraction and the attenuation of left ventricular remodeling.

PPARγ ligands decrease hydrostatic pressure-induced platelet aggregation and proinflammatory activity.

Hypertension is known to be associated with platelet overactivity, but the direct effects of hydrostatic pressure on platelet function remain unclear. The present study sought to investigate whether elevated hydrostatic pressure is responsible for platelet activation and to address the potential role of peroxisome proliferator-activated receptor-γ (PPARγ). We observed that hypertensive patients had significantly higher platelet volume and rate of ADP-induced platelets aggregation compared to the controls. In vitro, Primary human platelets were cultured under standard (0 mmHg) or increased (120, 180, 240 mmHg) hydrostatic pressure for 18 h. Exposure to elevated pressure was associated with morphological changes in platelets. Platelet aggregation and PAC-1 (the active confirmation of GPIIb/IIIa) binding were increased, CD40L was translocated from cytoplasm to the surface of platelet and soluble CD40L (sCD40L) was released into the medium in response to elevated hydrostatic pressure (180 and 240 mmHg). The PPARγ activity was up-regulated as the pressure was increased from 120 mmHg to 180 mmHg. Pressure-induced platelet aggregation, PAC-1 binding, and translocation and release of CD40L were all attenuated by the PPARγ agonist Thiazolidinediones (TZDs). These results demonstrate that platelet activation and aggregation are increased by exposure to elevated pressure and that PPARγ may modulate platelet activation induced by high hydrostatic pressure.

Aging attenuates the interarm diastolic blood pressure difference induced by one-arm exercise.

OBJECTIVES: It is known that one-arm exercise increases the interarm diastolic blood pressure difference (dIAD) in young individuals, but no research has been carried out in middle-aged and more senior populations. This study aimed to determine whether aging impacts the exercise-induced dIAD in healthy individuals. METHODS: Normotensive adults (n=120) were recruited and divided into the young (22.5±1.5 years), middle-aged (42.8±4.6 years), and senior (61.0±7.0 years) groups. The right arm exercise involved performing cycling movements at 60 times/min for 3 min. Bilateral brachial blood pressures (BPs) were simultaneously measured using two automatic BP measurement devices before (baseline), immediately (0), 5, 10, and 15 min after the exercise. The difference in bilateral diastolic BPs was calculated as BP l-r and its absolute value of at least 10 mmHg was considered as IAD. RESULTS: At baseline, the systolic blood pressure (SBP) l-r and diastolic blood pressure (DBP) l-r were similar in three age groups. One-arm exercise induced a marked decrease in DBP in the exercised arm, and then increased the prevalence of DBP l-r and dIAD in the three age groups in an age-dependent manner. The prevalence of dIAD increased from the baseline of zero to 85% at 0 min in young, 37% in middle-aged, and 30% in senior groups. One-arm exercise did not significantly alter the prevalence of SBP l-r and systolic IAD in the three groups. A reverse correlation was found between the DBP l-r 0 and ages (r=-0.359, P<0.05), but there was no correlation between aging and SBP l-r 0. CONCLUSION: Aging attenuates the levels and duration of the dIAD induced by one-arm exercise in healthy adults.

[Investigation on the relationship between the solar term of onset and syndrome types in 430 patients with acute myocardial infarction by circular statistical analysis].

OBJECTIVE: To study the relationship between the solar term of onset of acute myocardial infarction (AMI) and its syndrome types in traditional Chinese medicine (TCM). METHODS: The clinical data about 430 patients with AMI hospitalized in Foshan Hospital of TCM from February 4th 2003 (Beginning of Spring) to February 3rd 2008 (Beginning of Spring) were collected, and the solar term of onset as angle coordinate was regarded, then the peak phase of the onset solar term in each syndrome type of AMI was calculated by circular statistical analysis. RESULTS: Among 430 patients with AMI, 134 patients were considered to have qi stagnancy and blood stasis syndrome, 188 patients showed the syndrome of turbid sputum obstruction, 29 of them showed deficiency of yin-blood, and 79 showed deficiency of yang qi. The clinical manifestation of AMI was mainly asthenia syndrome (qi stagnancy and blood stasis+turbid sputum obstruction, 74.9%). According to the circular statistical analysis, the peak of the solar terms of AMI onset occurred at the Beginning of Spring in all cases (r=0.127 4, P<0.01), and standard deviation (s)=116.300 6 degree angle, showed it mainly occurred in winter and spring. As the peak of the onset of qi stagnancy and blood stasis occurred at Winter Solstice and Lesser Cold (r=0.200 5, P<0.01), its peak occurred in winter; the turbid sputum obstruction syndrome occurred at Spring Equinox (r=0.147 0, P<0.05), mainly in spring, yet the symptoms of above two peaks were generally mild. Besides, there was no significant difference in onset of the solar term in regard to onset of deficiency of yin-blood and deficiency of yang qi (both P>0.05). CONCLUSION: There is a close relationship between periodicity of the solar terms and onset of AMI. The main treatment for AMI is to expel turbid sputum, activate blood to resolve stasis and promote blood circulation to relieve pain; also the method of activating blood to resolve stasis is frequently contemplated in winter, and the method of expelling turbid sputum is the main strategy in spring.

[Construction of subtracted cDNA library by suppression subtractive hybridization for differentially expressed genes in eosinophils from asthma patients].

OBJECTIVE: To construct a subtracted cDNA library of differentially expressed genes in eosinophils from asthma patients. METHODS: Suppression subtractive hybridization (SSH) was used to isolate the cDNA fragments of differentially expressed genes in the eosinophils of asthma patients before and after treatment. The cDNA fragments were directly inserted into T/A cloning vector to establish the subtractive library, followed by amplification of the library through E. coli transformation with calcium chloride and screening of blue and white clones of the transformants. One hundred positive bacterial clones were randomly picked and identified by colony PCR. RESULTS: The amplified library contained more than 3,000 positive bacterial clones. Analysis of the randomly selected 100 white clones by PCR showed that 90% of the clones contained 100-500 bp inserts, which might be the cDNA fragments of differentially expressed genes in eosinophils of asthma patients before treatment. CONCLUSION: A subtracted cDNA library of differentially expressed genes in the eosinophils of asthma patients before and after treatment is constructed successfully by SSH and T/A cloning techniques, which lays a solid foundation for screening and cloning new specific differentially.expressed genes in the eosinophils of asthma patients.

[Study of genes that differentially expressed in eosinophils of patients with asthma by suppression subtractive hybridization technology].

OBJECTIVE: To study genes that differentially expressed in peripheral blood eosinophils of patient with asthmatic. METHODS: Total RNA extracted from eosinophils of patient at the time of exacerbation was taken as the tester and the total RNA from eosinophils of the same patient after improvement as driver. The ds cDNA was synthesized by SMART PCR cDNA Synthesis technology. The differentially expressed genes were obtained by suppression subtractive hybridization (SSH) technology and were further identified by Southern blot. RESULTS: Twelve differentially expressed genes including transformation growth factor beta activated kinase like (TAK1L) protein, cGMP gated channel protein were obtained. CONCLUSION: Increased expression of these genes were involved in the regulation of proinflammatory response, signal transduction, energy metabolism and cell apoptosis, which may help to clarify the molecular mechanism of eosinophils in asthma and may provide the theoretical base for finding out the new medicines towards eosinophils.

[Cloning of differentially expressed genes of eosinophils from asthmatic patients by suppression subtractive hybridization].

OBJECTIVE: To explore the molecular mechanism of eosinophils for its role in bronchial asthma. METHODS: The total RNA extracted from the eosinophils of patients during the onset of asthma was used as the tester and the total RNA obtained after treatment served as the driver. cDNA suppression subtractive hybridization (SSH) was performed using the protocols described in the Clontech SMART PCR cDNA Syn thesis Kit and PCR-Select cDNA Subtraction Kit. The subtracted cDNA was then inserted into T vector to generate subtracted cDNA library. Clones of the subtracted cDNA library were screened by hybridization and the insert sequence of the positive clones was compared with the sequence in the GenBank. RESULTS: A total of 400 clones selected from the subtracted cDNA library were amplified by PCR and about 85% of these clones contained inserts. Six differential cDNA fragments were acquired after two differential screening. These genes were involved in the regulation of proinflammatory response, signal transduction, energy metabolism and cell apoptosis. CONCLUSION: Differentially expressed genes of the eosinophils during the onset and the remission stage of bronchial asthma can be effectively cloned by SSH, which provides a solid foundation for clarifying the molecular mechanism of eosinophils in asthma and a theoretical base for clinical treatment and prevention of asthma.