Microcirculatory changes as a hallmark of aging in the heart and kidney / Cambios microcirculatorios como sello distintivo del envejecimiento en el corazón y riñón

SUMMARY: Changes in the microcirculation of multiple tissues and organs have been implicated as a possible mechanism in physiological aging. In particular, vascular endothelial growth factor is a secretory protein responsible for regulating angiogenesis via altering endothelial proliferation, survival, migration, extracellular matrix degradation and cell permeability. The aim of the present study was to evaluate the role of vascular endothelial growth factor in the progression of morphological alterations caused by physiological aging in the heart and kidney and to examine its relation to changes in capillary density. We used two age groups of healthy Wistar rats - 6- and 12-month- old. The expression of vascular endothelial growth factor was examined through immunohistochemistry and immunofluorescence and assessed semi-quantitatively. Changes in capillary density were evaluated statistically and correlated with the expression of vascular endothelial growth factor. We reported stronger immunoreactivity for vascular endothelial growth factor in the left compared to the right ventricle and also observed an increase in its expression in both ventricles in older animals. Contrasting results were reported for the renal cortex and medulla. Capillary density decreased statistically in all examined structures as aging progressed. The studied correlations were statistically significant in the two ventricles in 12-month-old animals and in the renal cortex of both age groups. Our results shed light on some changes in the microcirculation that take place as aging advances and likely contribute to impairment in the function of the examined organs.

Los cambios en la microcirculación de múltiples tejidos y órganos se han implicado como un posible mecanismo en el envejecimiento fisiológico. En particular, el factor de crecimiento endotelial vascular es una proteína secretora responsable de regular la angiogénesis mediante la alteración de la proliferación endotelial, la supervivencia, la migración, la degradación de la matriz extracelular y la permeabilidad celular. El objetivo del presente estudio fue evaluar el papel del factor de crecimiento del endotelio vascular en la progresión de las alteraciones morfológicas causadas por el envejecimiento fisiológico en el corazón y riñón y examinar su relación con los cambios en la densidad capilar. Utilizamos dos grupos de ratas Wistar sanas: 6 y 12 meses de edad. La expresión del factor de crecimiento del endotelio vascular se examinó mediante inmunohistoquímica e inmunofluorescencia y se evaluó semicuantitativamente. Los cambios en la densidad capilar se evaluaron estadísticamente y se correlacionaron con la expresión del factor de crecimiento del endotelio vascular. Informamos una inmunorreactividad más fuerte para el factor de crecimiento endotelial vascular en el ventrículo izquierdo en comparación con el derecho y también observamos un aumento en su expresión en ambos ventrículos en animales mayores. Se informaron resultados contrastantes para la corteza renal y la médula. La densidad capilar disminuyó estadísticamente en todas las estructuras examinadas a medida que avanzaba el envejecimiento. Las correlaciones estudiadas fueron estadísticamente significativas en los dos ventrículos en animales de 12 meses y en la corteza renal de ambos grupos de edad. Nuestros resultados arrojan luz sobre algunos cambios en la microcirculación que tienen lugar a medida que avanza el envejecimiento y probablemente contribuyan a un deterioro en la función de los órganos examinados.

Differential Analysis of Macular Structure and Microcirculation in Both Eyes of Patients With Myopic Anisometropia / 中国医学科学院学报

Objective To compare the macular structure and microcirculation in both eyes of the patients with myopic anisometropia.Methods Optical coherence tomography angiography(OCTA)was employed to scan the macular areas in both eyes of 44 patients with myopic anisometropia.The patients were assigned into high and low groups based on the refractive diopter,and the parameters such as retinal thickness,choroidal thickness,vascular density,and perfusion density in the macular areas of both eyes were compared between the two groups.Results Other macular areas except the central and external nasal areas and the choroid of the fovea in the high group were thinner than those in the low group(all P<0.05).There was no statistically significant difference in retinal vascular density or perfusion density in different areas between the two groups(all P>0.05).Conclusion In the patients with myopic anisometropia,most areas of the retina in the case of high myopia is thinner than that in the case of low myopia,while there is no difference in retinal vascular density or perfusion density in both eyes.

Effect of mild moxibustion with moxa stick and infrared mild moxibustion on skin blood perfusion at Waiguan (TE 5) / 中国针灸

OBJECTIVES@#To observe the changes of skin blood flow perfusion at Waiguan (TE 5) caused by mild moxibustion with moxa stick and infrared mild moxibustion using laser speckle contrast imaging technology, and to compare the microcirculatory effect during and after both moxibustion methods and explore the dose-response relationship of moxibustion.@*METHODS@#Twenty-four healthy participants were treated with mild moxibustion with moxa stick and infrared mild moxibustion at left Waiguan (TE 5). The record started when the skin temperature reached (44±1) °C, and both moxibustion methods were provided within this temperature range. The 20-minute moxibustion process was divided into four stages (5, 10, 15, and 20 min) using interpolation method, and each participant completed eight interventions with a minimum 24-hour interval between different interventions. The skin surface temperature of the left Waiguan (TE 5) was monitored when both moxibustion interventions were given for 10 min using a TES1306 thermocouple thermometer. The skin microcirculatory blood perfusion units (MBPU) of left Waiguan (TE 5) was measured using a PSIN-01087 laser speckle blood flow imager 1 min before moxibustion, at 5, 10, 15, 20 min during moxibustion and continuously for 20 min after moxibustion in each intervention.@*RESULTS@#The skin surface temperature of the left Waiguan (TE 5) remained within the range of (44±1) °C during both moxibustion methods, with no statistically significant difference (P>0.05). Compared with that before moxibustion, the MBPU of the left Waiguan (TE 5) was increased significantly at 5, 10, 15, and 20 min of both moxibustion methods (P<0.05, P<0.01). Compared with moxibustion for 10, 15 and 20 min, the MBPU of the left Waiguan (TE 5) of moxibustion for 5 min was lower in both moxibustion methods (P<0.01). For both moxibustion methods with the same moxibustion course, the MBPU of the left Waiguan (TE 5) 20 min after intervention was significantly higher than that at 1 min before moxibustion (P<0.001), and there was no significant difference in MBPU between 1 min before moxibustion and 20 min after moxibustion among different groups (P>0.05). Within the same moxibustion method, the MBPU of the left Waiguan (TE 5) 20 min after moxibustion with the intervention of 5 min was lower compared to that of 10, 15, and 20 min of moxibustion (P<0.001), with no significant differences between 10, 15, and 20 min of moxibustion (P>0.05).@*CONCLUSIONS@#When controlling the skin temperature at Waiguan (TE 5) within (44±1) °C, infrared mild moxibustion has similar effects on skin microcirculatory blood perfusion as traditional mild moxibustion with moxa sticks. From a dose-response perspective, microcirculation reached a stable state after 10 min of moxibustion, and moxibustion interventions lasting for more than 10 min shows better therapeutic effects.

The skin surface microcirculation of conception vessel, governor vessel and thoroughfare vessel in patients with primary dysmenorrhea / 中国针灸

OBJECTIVE@#To observe the skin surface microcirculation of acupoints of conception vessel, governor vessel and thoroughfare vessel in patients with primary dysmenorrhea using laser speckle contrast imaging (LSCI), and provide acupoint selection basis of acupuncture-moxibustion for primary dysmenorrhea.@*METHODS@#Ninety-nine healthy female college students with regular menstrual cycles (normal group) and 94 female college students with primary dysmenorrhea (dysmenorrhea group) were recruited. Before menstrual period, on the first day of menstruation, and on the third day after menstruation, LSCI was used to observe the surface microcirculation at the abdominal acupoints of conception vessel, i. e. Yinjiao (CV 7), Qihai (CV 6), Shimen (CV 5), Guanyuan (CV 4), Zhongji (CV 3) and Qugou (CV 2), acupoints of thoroughfare vessel, i. e. Huangshu (KI 16), Zhongzhu (KI 15), Siman (KI 14), Qixue (KI 13), Dahe (KI 12), Henggu (KI 11) and acupoints of lumbosacral region of governor vessel, i. e. Xuanshu (GV 5), Mingmen (GV 4), Yaoyangguan (GV 3), Yaoshu (GV 2) as well as two non-acupoints.@*RESULTS@#Before menstrual period, there was no significant difference in the surface blood perfusion of the acupoints between the dysmenorrhea group and the normal group (P>0.05). On the first day of menstruation, the surface blood perfusion of Xuanshu (GV 5), Mingmen (GV 4), Yaoyangguan (GV 3) and right Huangshu (KI 16) in the dysmenorrhea group was higher than that in the normal group (P<0.05, P<0.01). On the third day after menstruation, the surface blood perfusion of the right Henggu (KI 11) in the dysmenorrhea group was lower than that in the normal group (P<0.05).@*CONCLUSION@#In patients with primary dysmenorrhea, on the first day of menstruation, the surface blood perfusion of Xuanshu (GV 5), Mingmen (GV 4), Yaoyangguan (GV 3) of governor vessel, and the right Huangshu (KI 16) of thoroughfare vessel is increased, while on the third day after menstruation, the surface blood perfusion of the right Henggu (KI 11) of thoroughfare vessel is decreased. These findings might provide a basis for acupoint selection in the acupuncture-moxibustion treatment of primary dysmenorrhea.

Effectiveness of tibial transverse transport combined with modified neurolysis in treatment of diabetic foot ulcers / 中国修复重建外科杂志

OBJECTIVE@#To investigate the effectiveness of tibial transverse transport (TTT) combined with modified neurolysis in treatment of diabetic foot ulcer (DFU) through a prospective randomized controlled study.@*METHODS@#The patients with DFU and diabetic peripheral neuropathy, who were admitted between February 2020 and February 2022, were selected as the research objects, of which 31 cases met the selection criteria and were included in the study. The patients were divided into two groups by random number table method. The 15 patients in the trial group were treated with TTT combined with modified neurolysis, and the 16 patients in the control group received treatment with TTT alone. There was no significant difference in gender, age, duration of DFU, ulcer area, Wagner classification, as well as preoperative foot skin temperature, visual analogue scale (VAS) score, ankle-brachial index (ABI), motor nerve conduction velocity (MNCV) of the common peroneal nerve, MNCV of the tibial nerve, MNCV of the deep peroneal nerve, two-point discrimination (2-PD) of heel, and cross-sectional area (CSA) of the common peroneal nerve between the two groups ( P>0.05). The time for ulcer healing, foot skin temperature, VAS scores, ABI, 2-PD of heel, and CSA of the common peroneal nerve before operation and at 6 and 12 months after operation were recorded and compared between groups. The differences in MNCV of the common peroneal nerve, MNCV of the tibial nerve, and MNCV of the deep peroneal nerve between pre-operation and 12 months after operation were calculated.@*RESULTS@#All patients in both groups were followed up 12-24 months (mean, 13.9 months). The surgical incisions in both groups healed by first intention and no needle tract infections occurred during the bone transport phase. Ulcer wounds in both groups healed successfully, and there was no significant difference in the healing time ( P>0.05). During the follow-up, there was no ulcer recurrences. At 12 months after operation, the MNCV of the common peroneal nerve, the MNCV of the tibial nerve, and the MNCV of the deep peroneal nerve in both groups accelerated when compared to preoperative values ( P<0.05). Furthermore, the trial group exhibited a greater acceleration in MNCV compared to the control group, and the difference was significant ( P<0.05). The foot skin temperature, VAS score, ABI, 2-PD of heel, and CSA of the common peroneal nerve at 6 and 12 months after operation significantly improved when compared with those before operation in both groups ( P<0.05). The 2-PD gradually improved over time, showing significant difference ( P<0.05). The 2-PD of heel and VAS score of the trial group were superior to the control group, and the differences were significant ( P<0.05). There was no significant difference in ABI, foot skin temperature, and CSA of the common peroneal nerve between groups after operation ( P>0.05).@*CONCLUSION@#Compared with TTT alone, the TTT combined with modified neurolysis for DFU can simultaneously solve both microcirculatory disorders and nerve compression, improve the quality of nerve function recovery, and enhance the patient's quality of life.

Mechanism of Zhongfeng Xingnao Decoction in improving microcirculatory disorders in cerebral hemorrhage based on network pharmacology and molecular docking techniques / 中国中药杂志

This study aimed to explore the mechanism of Zhongfeng Xingnao Decoction(ZFXN) in intervening microcirculatory di-sorders in cerebral hemorrhage by network pharmacology and molecular docking techniques. The information on the components of ZFXN was obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database, and the predicted targets of chemical components were obtained from PubChem and SwissTargetPrediction. The relevant targets of cerebral hemorrhage and microcirculatory disorders were collected from the GeneCards database, and the common targets of the components and diseases were analyzed by the Database for Annotation, Visualization, and Integrated Discovery(DAVID) for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses. Visualization of the correlation network was carried out using Cytoscape software to further screen important chemical components for molecular docking prediction with disease targets. The animal experiment validation was performed using modified neurological severity score(mNSS), enzyme-linked immunosorbent assay(ELISA), quantitative real-time polymerase chain reaction(qRT-PCR), immunofluorescence, and Western blot to detect the effects of ZFXN intervention in mice with cerebral hemorrhage. The results showed that there were 31 chemical components and 856 targets in the four drugs contained in ZFXN, 173 targets for microcirculatory disorders in cerebral hemorrhage, and 57 common targets for diseases and components. The enrichment analysis showed that common targets were mainly involved in biological processes, such as cell proliferation and apoptosis, and signaling pathways, such as tumor pathway, viral infection, phosphoinositide-3-kinase/protein kinase B(PI3K/AKT) signaling pathway, and mitogen-activated protein kinase(MAPK) signaling pathway. Molecular docking results revealed that the common components β-sitosterol of Rhei Radix et Rhizoma, Notoginseng Radix et Rhizoma, and Ginseng Radix et Rhizoma Rubra showed good docking with proto-oncogene tyrosine-protein kinase(SRC), signal transducer and activator of transcription 3(STAT3), phosphoinositide-3-kinase catalytic alpha polypeptide gene(PIK3CA), recombinant protein tyrosine phosphatase non receptor type 11(PTPN11), AKT1, epidermal growth factor receptor(EGFR), calcium adhesion-associated protein beta 1(CTNNB1), vascular endothelial growth factor A(VEGFA), and tumor protein p53(TP53). Moreover, sennoside E of Rhei Radix et Rhizoma showed good docking with MAPK1. The results revealed that the ZFXN relieved the neural injury in mice with cerebral hemorrhage, decreased the expression of S100 calcium-binding protein B(S100β), neuron specific enolase(NSE), matrix metalloproteinase 9(MMP9), tumor necrosis factor α(TNF-α), interleukin 1β(IL-1β), SRC, EGFR, CTNNB1, VEGFA, TP53, glial fibrillary acidic protein(GFAP), and leukocyte differentiation antigen 86(CD86), and increased the expression of p-PI3K, p-AKT, and zona occludens 1(ZO-1). The results indicate that ZFXN may inhibit neuronal apoptosis and inflammatory response through PI3K/AKT/p53 pathway to protect the blood-brain barrier, thereby slowing down microcirculatory impairment in cerebral hemorrhage.

Correlation between four limbs perfusion index and lactic acid in patients with severe neurological diseases / 中华危重病急救医学

OBJECTIVE@#To observe the correlation between the four limbs perfusion index (PI) and blood lactic acid in patients with neurosis, and evaluate the predictive value of PI on microcirculation perfusion metabolic disorder in patients with neurosis.@*METHODS@#A prospective observational study was conducted. Adult patients admitted to the department of neurological intensive care unit (NICU) of the First Affiliated Hospital of Xinjiang Medical University from July 1 to August 20 in 2020 were enrolled. Under the condition of indoor temperature controlled at 25 centigrade, all patients were placed in the supine position, and the blood pressure, heart rate, PI of both fingers and thumb toes and arterial blood lactic acid were measured within 24 hours and 24-48 hours after NICU. The difference of four limbs PI at different time periods and its correlation with lactic acid were compared. Receiver operator characteristic curve (ROC curve) was used to evaluate the predictive value of four limbs PI on patients with microcirculatory perfusion metabolic disorder.@*RESULTS@#A total of 44 patients with neurosis were enrolled, including 28 males and 16 females; average age (61.2±16.5) years old. There were no significant differences in PI of the left index finger and the right index finger [2.57 (1.44, 4.79) vs. 2.70 (1.25, 5.33)], PI of the left toe and the right toe [2.09 (0.85, 4.76) vs. 1.88 (0.74, 4.32)] within 24 hours after entering the NICU, and the PI of the left index finger and the right index finger [3.17 (1.49, 5.07) vs. 3.14 (1.33, 5.36)], PI of the left toe and the right toe [2.07 (0.75, 5.20) vs. 2.07 (0.68, 4.67)] at 24-48 hours after NICU admission (all P > 0.05). However, compared to the PI of the upper and lower limbs on the same side, except for the 24-48 hours after ICU of the PI difference between the left index finger and the left toe (P > 0.05), the PI of the toe was lower than that of the index finger at the other time periods (all P < 0.05). The correlation analysis showed that the PI value of four limbs of patients in both time periods were significantly negatively correlated with arterial blood lactic acid (the r values of the left index finger, the right index finger, the left toe and the right toe were -0.549, -0.482, -0.392 and -0.343 respectively within 24 hours after entering the NICU; the r values of the left index finger, the right index finger, the left toe and the right toe were -0.331, -0.292, -0.402 and -0.442 respectively after entering the NICU 24-48 hours, all P < 0.05). Taking lactic acid ≥ 2 mmol/L as the diagnostic standard for metabolic disorder of microcirculation perfusion (total 27 times, accounting for 30.7%). The efficacy of four limbs PI in predicting microcirculation perfusion metabolic disorder were compared. ROC curve analysis showed that the area under the curve (AUC) and 95% confidence interval (95%CI) of left index finger, right index finger, left toe and right toe predicting microcirculation perfusion metabolic disorder were 0.729 (0.609-0.850), 0.767 (0.662-0.871), 0.722 (0.609-0.835), 0.718 (0.593-0.842), respectively. There was no significant difference in AUC compare with each other (all P > 0.05). The cut-off value of PI of right index finger for predicting microcirculation perfusion metabolic disorder was 2.46, the sensitivity was 70.4%, the specificity was 75.4%, the positive likelihood ratio was 2.86, and the negative likelihood ratio was 0.30.@*CONCLUSIONS@#There are no significant differences in PI of bilateral index fingers, bilateral toes in patients with neurosis. However, unilateral upper and lower limbs showed lower PI in the toe than in the index finger. There is a significantly negatively correlation between PI and arterial blood lactic acid in all four limbs. PI can predict the metabolic disorder of microcirculation perfusion, and its cut-off value is 2.46.

Design and implementation of a modular pulse wave preprocessing and analysis system based on a new detection algorithm / 生物医学工程学杂志

As one of the standard electrophysiological signals in the human body, the photoplethysmography contains detailed information about the blood microcirculation and has been commonly used in various medical scenarios, where the accurate detection of the pulse waveform and quantification of its morphological characteristics are essential steps. In this paper, a modular pulse wave preprocessing and analysis system is developed based on the principles of design patterns. The system designs each part of the preprocessing and analysis process as independent functional modules to be compatible and reusable. In addition, the detection process of the pulse waveform is improved, and a new waveform detection algorithm composed of screening-checking-deciding is proposed. It is verified that the algorithm has a practical design for each module, high accuracy of waveform recognition and high anti-interference capability. The modular pulse wave preprocessing and analysis software system developed in this paper can meet the individual preprocessing requirements for various pulse wave application studies under different platforms. The proposed novel algorithm with high accuracy also provides a new idea for the pulse wave analysis process.

Effect of superfine powder and aqueous extract of Polygonati Rhizoma on rats with natural perimenopausal syndrome / 中国中药杂志

This study aims to examine the effect of superfine powder and aqueous extract of Polygonati Rhizomaon on natural perimenopausal syndrome in rats and explore the underlying mechanism. To be specific, a total of 60 female SD rats(14-15 months old) with estrous cycle disorder were screened by the vaginal smear and randomized into model control group, β-estradiol 3-benzoate group(0.1 mg·kg~(-1)), superfine powder of Polygonati Rhizoma group(0.25, 0.5 g·kg~(-1)) and aqueous extract of Polygonati Rhizoma group(0.25, 0.5 g·kg~(-1)), and another 10 female SD rats(14-15 months old) were selected as the youth control group. The administration lasted 6 weeks. Then the perimenopausal syndrome-related indexes such as body temperature, microcirculatory blood flow of face and ear, vertigo period, salivary secretion, grip force, and bone strength were determined and open field test was conducted. The immune system-related indexes such as the wet weight and index of thymus and spleen, percentage of T lymphocytes and subgroups in peripheral blood, and hematological indexes were measured. In addition, the ovary-related indexes such as estrous cycle, the wet weight and index of uterus and ovary, ovarian tissue morphology, and cell apoptosis were determined. Moreover, hypothalamus-pituitary-ovary axis(HPO)-related indexes such as serum sex hormone levels, cytochrome P450 family 11 subfamily A member 1(CYP11A1), cytochrome P450 family 19 subfamily A member 1(CYP19A1), and cytochrome P450 family 17 subfamily A member 1(P450 17A1) in ovarian tissue were measured. The results showed that the superfine powder and aqueous extract of Polygonati Rhizoma significantly decreased body temperature(anal, facial and dorsal temperature), microcirculatory blood flow in the ear, and vertigo period, increased salivary secretion, grip force, bone strength, total distance and total speed in the open field test, wet weight and index of thymus and spleen, lymphocyte ratio, CD3~+ level, and CD4~+/CD8~+ ratio, reduced neutrophil number and ratio, estrous cycle disorder ratio, and number of ovarian apoptotic cells, raised wet weight and index of uterus, wet weight of ovary, levels of inhibin B(INHB), estradiol(E_2), anti-müllerian hormone(AMH), and ovarian CYP11A1 and CYP19A1, decreased follicle-stimulating hormone(FSH) and luteinizing hormone(LH) content, and improved ovarian tissue morphology. It is suggested that the superfine powder and aqueous extract of Polygonati Rhizoma can improve the symptoms associated with natural perimenopausal syndrome in rats and enhance ovarian function and immune function. The mechanism is that they regulate HPO axis function by increasing estrogen synthesis.

Effects of Compound Danshen Dripping Pills on Ventricular Remodeling and Cardiac Function after Acute Anterior Wall ST-Segment Elevation Myocardial Infarction (CODE-AAMI): Protocol for a Randomized Placebo-Controlled Trial / 中国结合医学杂志

BACKGROUND@#Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction.@*OBJECTIVE@#This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale.@*METHODS@#This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment.@*DISCUSSION@#This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411).

Mean platelet volume and neutrophil to lymphocyte ratio in patients with tinnitus: a case-control study / Volume plaquetário médio e relação neutrófilos/linfócitos em pacientes com zumbido: estudo de caso-controle

Abstract Introduction: Different theories have been proposed on the etiology of tinnitus, including metabolic and audiologic causes. We suggest that mean platelet volume and neutrophil to lymphocyte ratio levels change in tinnitus, indicating microcirculatory disturbance and inflammatory process in the etiopathogenesis of tinnitus. Objectives: We aimed to evaluate the mean platelet volume and neutrophil to lymphocyte ratio in patients with tinnitus in comparison to healthy controls. Methods: Retrospective case-control study. Two-hundred and eighty-seven patients aged 18-59 years and diagnosed with tinnitus in the Ear, Nose, and Throat Clinic between December 2014 and May 2017 (patient group) and 275 healthy individuals who applied for a hearing screening within the same time period (control group). Demographics, concomitant diseases, laboratory results, and audiometric data were recorded. Mean platelet volume and neutrophil to lymphocyte ratio were the outcome measures. Patients with hearing loss due to presbycusis or another reasons, and patients with anatomical disorders in the external and middle ear were excluded from the study by using physical examinations, pure audio audiometry results and radiological imaging. The upper age limit was set at 59 to exclude presbycusis patients. Results: The ratio of female patients was higher in patient group than control group (58.5%, n = 168 vs. 49.4%, n= 127; respectively; p = 0.033). The mean age of patient group was significantly higher than those of control group (44.89 ± 10.96 years and 38.37 ± 10.65 years, respectively; p = 0.001). The percentage of subjects with high mean platelet volume level was significantly higher in patient group than control group (9.4%, n = 27, and 3.1%, n = 8 respectively; p = 0.008). The mean neutrophil to lymphocyte ratio was higher in patients with tinnitus than control group (1.95 ± 1.02 and 1.67 ±0.57, p = 0.012). A neutrophil to lymphocyte ratio level of 2.17 and above is associated with 1.991 times higher risk of tinnitus (odds ratio = 1.99, 95% confidence interval 1.31-3.02). Conclusion: High mean platelet volume and neutrophil to lymphocyte ratio values are associated with idiopathic tinnitus, suggesting the role of vascular pathologies in etiology of tinnitus. Tinnitus may be a sign of underlying systemic or local disorders. Therefore, patients with tinnitus should undergo detailed evaluation including hematological indices.

Resumo Introdução: Diferentes teorias já foram propostas sobre a etiologia do zumbido, inclusive causas metabólicas e audiológicas. Acreditamos que os níveis do volume plaquetário médio e da relação neutrófilos/linfócitos se alteram no zumbido, sugerem distúrbio microcirculatório e processo inflamatório na etiopatogenia do zumbido. Objetivo: Avaliar o volume plaquetário médio e a relação neutrófilos/linfócitos em pacientes com zumbido em comparação com controles saudáveis. Método: Estudo de caso-controle retrospectivo, com 287 pacientes entre 18 e 59 anos e diagnosticados com zumbido na Clínica de Otorrinolaringologia entre dezembro de 2014 e maio de 2017 (grupo pacientes) e 275 indivíduos saudáveis que solicitaram uma triagem auditiva no mesmo período (grupo controle). Foram registrados dados demográficos, doenças concomitantes, resultados laboratoriais e dados audiométricos. O volume plaquetário médio e a relação neutrófilos/linfócitos foram as medidas de desfecho. Pacientes com perda auditiva por presbiacusia ou por outros motivos e pacientes com distúrbios anatômicos na orelha externa e média foram excluídos do estudo por meio de exame físico, resultados de audiometria tonal pura e imagens radiológicas. O limite de idade superior foi fixado em 59 anos para excluir pacientes com presbiacusia. Resultados: A proporção de pacientes do sexo feminino foi maior no grupo de pacientes do que no grupo controle (58,5%, n = 168 vs. 49,4%, n = 127; respectivamente; p = 0,033). A média de idade do grupo de pacientes era significantemente maior do que a do grupo controle (44,89 ± 10,96 anos e 38,37 ± 10,65 anos, respectivamente; p = 0,001). A porcentagem de indivíduos com nível alto de volume plaquetário médio foi significantemente maior no grupo de pacientes do que no grupo controle (9,4%, n = 27 e 3,1%, n = 8, respectivamente; p = 0,008). A relação neutrófilos/linfócitos média foi maior nos pacientes com zumbido do que no grupo controle (1,95 ± 1,02 e 1,67 ±0,57, p = 0,012). Um nível de relação neutrófilos/linfócitos de 2,17 e acima está associado a um risco 1,991 vez maior de zumbido (odds ratio = 1,99, Intervalo de Confiança de 95% 1,31 a 3,02). Conclusão: Altos valores de volume plaquetário médio e relação neutrófilos/linfócitos estão associados ao zumbido idiopático, sugerem o papel de doenças vasculares na etiologia do zumbido. O zumbido pode ser um sinal de distúrbios sistêmicos ou locais subjacentes. Portanto, pacientes com zumbido devem ser submetidos a uma avaliação detalhada, inclusive índices hematológicos.

Index of microcirculatory resistance: state-of-the-art and potential applications in computational simulation of coronary artery disease / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The dysfunction of coronary microcirculation is an important cause of coronary artery disease (CAD). The index of microcirculatory resistance (IMR) is a quantitative evaluation of coronary microcirculatory function, which provides a significant reference for the prediction, diagnosis, treatment, and prognosis of CAD. IMR also plays a key role in investigating the interaction between epicardial and microcirculatory dysfunctions, and is closely associated with coronary hemodynamic parameters such as flow rate, distal coronary pressure, and aortic pressure, which have been widely applied in computational studies of CAD. However, there is currently a lack of consensus across studies on the normal and pathological ranges of IMR. The relationships between IMR and coronary hemodynamic parameters have not been accurately quantified, which limits the application of IMR in computational CAD studies. In this paper, we discuss the research gaps between IMR and its potential applications in the computational simulation of CAD. Computational simulation based on the combination of IMR and other hemodynamic parameters is a promising technology to improve the diagnosis and guide clinical trials of CAD.

Inspiration from the research advances in microcirculatory dysfunction to the treatment of burn shock and burn septic shock / 中华烧伤杂志

Microcirculatory dysfunction is an important pathophysiological change of shock. In the last decade, many researches on the mechanism of microcirculatory dysfunction have been involved in areas such as the glycocalyx damage of vascular endothelial cells, macrocirculation- microcirculation discoupling, vascular hyporeactivity, and microcirculation monitoring. Accordingly, this paper discussed how these research findings can be applied to burn patients, with the aim of alerting the clinicians to improving microcirculation, and maintaining hemodynamic coordination during the treatment of burn shock and burn septic shock. In addition, with the development of accurate and reliable microcirculation monitoring techniques, it is necessary to carry out multi-center clinical trials to reveal the clinical significance of target-oriented shock resuscitation protocol combining macrocirculatory and microcirculatory parameters.

Peripapillary microvascular parameters in unilateral open-angle glaucoma using the optical coherence tomography-angiography

Objective@#This study compared the peripapillary retinal nerve fiber layer (pRNFL) microangiographic properties [vessel area density (VAD) and blood flux index (BFI)] of unilateral open-angle glaucomatous eyes to contralateral eyes-at-risk, and to eyes of healthy age- and sex-matched subjects.@*Methods@#This was a single-center, case-control study of Filipinos diagnosed with unilateral primary openangle glaucoma (POAG) or normal-tension glaucoma (NTG). Mean overall and quadrantal VAD and BFI of the three groups were measured with optical coherence tomography- angiography (OCT-A). Area under the receiver operating characteristic (AROC) was used to measure diagnostic ability.@*Results@#Twenty-two (22) glaucomatous subjects (15 POAG and 7 NTG eyes), 22 contralateral eyes-at-risk, and 22 normal eyes from age- and sex-matched control subjects completed the study. Eyes with glaucoma showed lower mean overall VAD (40%) and BFI (0.37) compared to eyes-at-risk (44.4% and 0.42, respectively; p <0.001) and control eyes (45.6% and 0.44, respectively; p <0.001). Mean VAD and BFI values of eyes-at-risk and control groups did not significantly differ from each other. Overall pRNFL thickness showed highest diagnostic accuracy for glaucoma (AROC = 0.97), followed by VAD (0.94), and BFI (0.88) (p=0.46).@*Conclusion@#VAD and BFI were significantly diminished in unilateral open-angle glaucoma, suggesting that the utility of OCT-A in the detection of glaucoma is comparable to pRNFL thickness.

Influence of Acupuncture on Microcirculation Perfusion of Pericardium Meridian and Heart in Acute Myocardial Ischemia Model Rats / 中国结合医学杂志

OBJECTIVE@#To observe the influence of acupuncture on microcirculation perfusion of the pericardium meridian and heart in acute myocardial ischemia (AMI) rats and evaluate whether acupuncture can simultaneously affect the meridians and corresponding viscera. Additionally, acupoints at different meridians were compared and whether they exert the same effects was discussed.@*METHODS@#Totally 32 Sprague-Dawley rats were subjected to left anterior descending (LAD) ligation to develop an AMI model. Rats were divided into 4 groups, including AMI, acupuncture Neiguan (PC 6), Lieque (LU 7) and Qiansanli (LI 10) groups (n=8). Eight rats received only thoracotomy (sham-operated group). The rats in the acupuncture groups received manual acupuncture at PC 6, LU 7 and LI 10 acupoints for 15 min, respectively. The microcirculation perfusion of pericardium meridian and heart was monitored by laser speckle perfusion imager (LSPI) before, during and after acupuncture manipulation for 15 min. Subsequently, the perfusion unit (PU) was calculated and analyzed by PSI System.@*RESULTS@#After LAD, compared to pre-acupuncture stage, the heart microcirculation perfusion (HMP) in the AMI group decreased continuously at during-acupuncture (P>0.05) and post-acupuncture stages (P0.05). Compared to pre-acupuncture stage, the PMP and HMP in PC 6 group significantly increased during acupuncture manipulation (both P0.05); however, they were significantly reduced after acupuncture manipulation (both P<0.05). Additionally, HMP of LI 10 group was decreased significantly during acupuncture, especially compared to pre-acupuncture stage (P<0.05).@*CONCLUSIONS@#Acupuncture at PC 6 obviously increased the PMP and HMP in AMI rats, and the effects were superior to at LU 7 and LI 10 acupoints. It was further confirmed that acupuncture promoted qi and blood circulation, indicating that acupoint specificity exists and features a meridian-propagated effect.

Protective Mechanism of Electroacupuncture on Peripheral Neurotoxicity Induced by Oxaliplatin in Rats / 中国结合医学杂志

OBJECTIVE@#To study the effect of electroacupuncture (EA) on oxaliplatin-induced peripheral neuropathy (OIPN) in rats.@*METHODS@#Male Sprague-Dawley rats were equally divided into 3 groups using a random number table: the control group, the OIPN group, and the EA (OIPN + EA) group, with 10 rats in each. The time courses of mechanical, cold sensitivity, and microcirculation blood flow intensity were determined. The morphology of the dorsal root ganglion (DRG) was observed by electron microscopic examination. The protein levels of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and the transient receptor potential (TRP) protein family in DRGs were assayed by Western blot.@*RESULTS@#EA treatment significantly reduced mechanical allodynia and cold allodynia in OIPN rats (P<0.01). Notably, oxaliplatin treatment resulted in impaired microcirculatory blood flow and pathomorphological defects in DRGs (P<0.01). EA treatment increased the microcirculation blood flow and attenuated the pathological changes induced by oxaliplatin (P<0.01). In addition, the expression levels of Nrf2 and HO-1 were down-regulated, and the TRP protein family was over-expressed in the DRGs of OIPN rats (P<0.01). EA increased the expression levels of Nrf2 and HO-1 and decreased the level of TRP protein family in DRG (P<0.05 or P<0.01).@*CONCLUSION@#EA may be a potential alternative therapy for OIPN, and its mechanism may be mainly mediated by restoring the Nrf2/HO-1 signaling pathway.

Influence of Microcirculatory Dysfunction on Myocardial Injury after Cardiopulmonary Resuscitation / 生物医学与环境科学（英文）

Objective@#This study aimed to examine the effects of microcirculatory dysfunction and 654-1 intervention after cardiopulmonary resuscitation on myocardial injury.@*Methods@#Landrace pigs were divided into a sham operation group (S group, n= 6), ventricular fibrillation control group (VF-C group, n= 8) and 654-1 intervention group (VF-I group, n= 8). Hemodynamics was recorded at baseline, at recovery of spontaneous circulation (ROSC), and 1 h, 2 h, 4 h and 6 h thereafter. Sidestream dark field (SDF) technology was used to evaluate and monitor the microcirculation flow index, total vessel density, perfusion vessel ratio, De-Backer score, and perfusion vessel density in animal viscera at various time points.@*Results@#After administration of 654-1 at 1.5 h post-ROSC, the hemodynamics in the VF-I group, as compared with the VF-C group, was significantly improved. The visceral microcirculation detected by SDF was also significantly improved in the VF-I group. As observed through electron microscopy, significantly less myocardial tissue injury was present in the VF-I group than the VF-C group.@*Conclusion@#Administration of 654-1 inhibited excessive inflammatory by improving the state of visceral microcirculation.

Resuscitation fluids as drugs: targeting the endothelial glycocalyx / 中华医学杂志(英文版)

Fluid resuscitation is an essential intervention in critically ill patients, and its ultimate goal is to restore tissue perfusion. Critical illnesses are often accompanied by glycocalyx degradation caused by inflammatory reactions, hypoperfusion, shock, and so forth, leading to disturbed microcirculatory perfusion and organ dysfunction. Therefore, maintaining or even restoring the glycocalyx integrity may be of high priority in the therapeutic strategy. Like drugs, however, different resuscitation fluids may have beneficial or harmful effects on the integrity of the glycocalyx. The purpose of this article is to review the effects of different resuscitation fluids on the glycocalyx. Many animal studies have shown that normal saline might be associated with glycocalyx degradation, but clinical studies have not confirmed this finding. Hydroxyethyl starch (HES), rather than other synthetic colloids, may restore the glycocalyx. However, the use of HES also leads to serious adverse events such as acute kidney injury and bleeding tendencies. Some studies have suggested that albumin may restore the glycocalyx, whereas others have suggested that balanced crystalloids might aggravate glycocalyx degradation. Notably, most studies did not correct the effects of the infusion rate or fluid volume; therefore, the results of using balanced crystalloids remain unclear. Moreover, mainly animal studies have suggested that plasma may protect and restore glycocalyx integrity, and this still requires confirmation by high-quality clinical studies.

Effects of dexmedetomidine on hemodynamic, oxygenation, microcirculation, and inflammatory markers in a porcine model of sepsis

Purpose: To determine whether dexmedetomidine aggravates hemodynamic, metabolic variables, inflammatory markers, and microcirculation in experimental septic shock. Methods: Twenty-four pigs randomized into: Sham group (n = 8), received saline; Shock group (n = 8), received an intravenous infusion of Escherichia coli O55 (3 × 109 cells/mL, 0.75 mL/kg, 1 hour); Dex-Shock group (n = 8), received bacteria and intravenous dexmedetomidine (bolus 0.5 mcg/kg followed by 0.7 mcg/kg/h). Fluid therapy and/ornorepinephrine were administered to maintain a mean arterial pressure > 65 mmHg. Hemodynamic, metabolic, oxygenation, inflammatory markers, and microcirculation were assessed at baseline, at the end of bacterial infusion, and after 60, 120, 180, and 240 minutes. Results: Compared to Shock group, Dex-Shock group presented a significantly increased oxygen extraction ratio at T180 (23.1 ± 9.7 vs. 32.5 ± 9.2%, P = 0.0220), decreased central venous pressure at T120 (11.6 ± 1 vs. 9.61 ± 1.2 mmHg, P = 0.0214), mixed-venous oxygen saturation at T180 (72.9 ± 9.6 vs. 63.5 ± 9.2%, P = 0.026), and increased plasma lactate (3.7 ± 0.5 vs. 5.5 ± 1 mmol/L, P = 0.003). Despite the Dex-Shock group having a better sublingual vessel density at T240 (12.5 ± 0.4 vs. 14.4 ± 0.3 mL/m2; P = 0.0003), sublingual blood flow was not different from that in the Shock group (2.4 ± 0.2 vs. 2.4 ± 0.1 mL/kg, P = 0.4418). Conclusions: Dexmedetomidine did not worsen the hemodynamic, metabolic, inflammatory, or sublingual blood flow disorders resulting from septic shock. Despite inducing a better sublingual vessel density, dexmedetomidine initially and transitorily increased the mismatch between oxygen supply and demand.

Comparação entre Dois Escores de Risco quanto à Predição de Obstrução Microvascular Coronariana durante a Intervenção Percutânea Primária / The Comparison between Two Risk Scores as for the Prediction of Coronary Microvascular Obstruction during Primary Percutaneous Intervention

Resumo Fundamento: Para pacientes com infarto do miocárdio com elevação do segmento ST (IAMCST) que sofrem de obstrução coronariana microvascular funcional e estrutural (OCM) subsequente, nenhuma abordagem terapêutica específica e definitiva de atenuação foi comprovada como válida em testes de larga escala atuais, o que destaca a necessidade de abordar seu reconhecimento precoce. Objetivos: Este estudo teve como objetivo comparar o desempenho de dois escores de risco clínico com uma medida objetiva de OCM durante intervenção coronária percutânea (ICP) em casos de IAMCST Métodos: A medição do índice de resistência microcirculatória (IRM) foi realizada e os parâmetros clínicos e angiográficos basais também foram registrados. Os pacientes foram divididos em entre os grupos OM (obstrução microvascular) e NOM (não-obstrução microvascular), de acordo com o valor de IRM pós-procedimento. O risco de OCM foi avaliado para todos os participantes pelos escores preditivos SAK e ATI, respectivamente. Cada sistema foi calculado somando-se as pontuações de todas as variáveis. As curvas de características do operador receptor (ROC) e a área sob a curva (AUC) de dois modelos de risco foram utilizadas para avaliar o desempenho discriminatório. Um ecocardiograma foi realizado sete dias após o procedimento para avaliar a fração de ejeção do ventrículo esquerdo (FEVE). Um valor P bicaudal de <0,05 foi considerado estatisticamente significativo. Resultados: Entre os 65 pacientes elegíveis com IAMCST, 48 foram alocados no grupo NOM e 17 no grupo OM, com uma incidência de OCM de 26,15%. Não houve diferença significativa na AUC entre os dois escores. A FEVE avaliada para o grupo NOM foi maior do que para o grupo OM. Conclusão: Os escores SAK e ATI tiveram bom desempenho para estimar o risco de OCM após ICP primário para pacientes com IAMCST.

Abstract Background: For patients with ST-segment elevation myocardial infarction (STEMI) that are suffering from subsequent coronary microvascular functional and structural obstruction (CMVO), no specific and definitive therapeutic approaches of attenuation have been proven valid in up-to-date large-scale tests, which highlights the urge to address its early recognition. Objectives: This study aimed to compare the performance of two clinical risk scores with an objective measurement of CMVO during percutaneous coronary intervention (PCI) with STEMI. Methods: The Index of Microcirculatory Resistance (IMR) measurement was conducted and the baseline clinical and angiographic parameters were also recorded. The patients were divided into MO (Microvascular obstruction) or NMO (Non-microvascular obstruction) groups according to the post-procedure IMR value. The CMVO risk was evaluated for all participants by SAK and ATI predictive scores, respectively. Each system was calculated by summing the scores of all variables. The receiver operator characteristic (ROC) curves and the area under the curve (AUC) of two risk models were used to evaluate the discriminatory performance. An echocardiography was performed seven days after the procedure to evaluate left ventricular ejection fraction (LVEF). A two-sided P-value of <0.05 was considered statistically significant. Results: Among the 65 eligible STEMI patients, 48 patients were allocated in the NMO group and 17 in the MO group, with a CMVO incidence of 26.15%. There was no significant difference in the AUC between both scores. The LVEF evaluated for the NMO group was higher than that of MO group. Conclusion: Both SAK and ATI scores performed well in estimating CMVO risk after primary PCI for STEMI patients.