Association between lactic acidosis and multiple organ dysfunction syndrome after cardiopulmonary bypass.

Background: The relationship between hyperlactatemia and prognosis after cardiopulmonary bypass (CPB) is controversial, and some studies ignore the presence of lactic acidosis in patients with severe hyperlactacemia. This study explored the association between lactic acidosis (LA) and the occurrence of multiple organ dysfunction syndrome (MODS) after cardiopulmonary bypass. Methods: This study was a post hoc analysis of patients who underwent cardiac surgery between February 2017 and August 2018 and participated in a prospective study at Taizhou Hospital. The data were collected at: ICU admission (H0), and 4, 8, 12, 24, and 48 h after admission. Blood lactate levels gradually increased after CPB, peaking at H8 and then gradually decreasing. The patients were grouped as LA, hyperlactatemia (HL), and normal control (NC) based on blood test results 8 h after ICU admission. Basic preoperative, perioperative, and postoperative conditions were compared between the three groups, as well as postoperative perfusion and oxygen metabolism indexes. Results: There were 22 (19%), 73 (64%), and 19 (17%) patients in the LA, HL, and NC groups, respectively. APACHE II (24h) and SOFA (24h) scores were the highest in the LA group (P < 0.05). ICU stay duration was the longest for the LA group (48.5 (42.5, 50) h), compared with the HL (27 (22, 48) h) and NC (27 (25, 46) h) groups (P = 0.012). The LA group had the highest incidence of MODS (36%), compared with the HL (14%) and NC (5%) groups (P = 0.015). In the LA group, the oxygen extraction ratio (O2ER) was lower (21.5 (17.05, 32.8)%) than in the HL (31.3 (24.8, 37.6)%) and the NC group (31.3 (29.0, 35.4) %) (P = 0.018). In the univariable analyses, patient age (OR = 1.054, 95% CI [1.003-1.109], P = 0.038), the LA group (vs. the NC group, (OR = 10.286, 95% CI [1.148-92.185], P = 0.037), and ΔPCO2 at H8 (OR = 1.197, 95% CI [1.022-1.401], P = 0.025) were risk factor of MODS after CPB. Conclusions: We speculated that there was correlation between lactic acidosis and MODS after CPB. In addition, LA should be monitored intensively after CPB.

Long-term oral administration of hyperoside ameliorates AD-related neuropathology and improves cognitive impairment in APP/PS1 transgenic mice.

Alzheimer's disease (AD) is a highly prevalent neurodegenerative disorder characterized by the pathological hallmarks of ß-amyloid plaque deposits, tau pathology, inflammation, and cognitive decline. Hyperoside, a flavone glycoside isolated from Rhododendron brachycarpum G. Don (Ericaceae), has neuroprotective effects against Aß both in vitro and in vivo. However, whether hyperoside could delay AD pathogenesis remains unclear. In the present study, we observed if chronic treatment with hyperoside can reverse pathological progressions of AD in the APP/PS1 transgenic mouse model. Meanwhile, we attempted to elucidate the molecular mechanisms involved in regulating its effects. After 9 months of treatment, we found that hyperoside can improve spatial learning and memory in APP/PS1 transgenic mice, reduce amyloid plaque deposition and tau phosphorylation, decrease the number of activated microglia and astrocytes, and attenuate neuroinflammation and oxidative stress in the brain of APP/PS1 mice. These beneficial effects may be mediated in part by influencing reduction of BACE1 and GSK3ß levels. Hyperoside confers neuroprotection against the pathology of AD in APP/PS1 mouse model and is emerging as a promising therapeutic candidate drug for AD.

Dynamics of peripheral immune cells and their HLA-G and receptor expressions in a patient suffering from critical COVID-19 pneumonia to convalescence.

OBJECTIVES: Host immune responses are indispensable to combat the disease. We report the dynamics of peripheral immune cells, cytokines, and human leucocyte antigen-G (HLA-G) and its receptor expressions in a patient suffering from critical COVID-19 pneumonia to convalescence. METHODS: Clinical data of the patient were collected from medical records. The expressions of HLA-G and receptors ILT2, ILT4 and KIR2DL4 in peripheral immune cells were measured with flow cytometry. RESULTS: From critical COVID-19 to the convalescent stage, early lymphopenia was improved (median: 0.6 × 109 L-1 vs. 0.9 × 109 L-1, P = 0.009), and an obvious fluctuation in WBC and neutrophil counts was observed. Initially, low levels of CD4+ T cells (from 120 to 528 µL-1) and CD8+ T cells (from 68 to 362 µL-1) gradually increased to normal levels. Meanwhile, high IL-6 (from 251.8 to 6.32 pg mL-1), IL-10 (from 39.53 to 5.21 pg mL-1) and IFN-γ (from 13.55 to 3.16 pg mL-1) levels decreased, and IL-4 (from 2.36 to 3.19 pg mL-1) and TNF-α (from 2.27 to 20.2 pg mL-1) levels increased quickly when the viral RNA returned negative. Moreover, the percentage of HLA-G+ T cells, B cells and monocytes follows high-low-high pattern, while the percentage of receptors ILT2-, ILT4- and KIR2DL4-expressing cells remained relatively stable. CONCLUSION: Our findings provide valuable information on the dynamics of early peripheral immunological responses in SARS-CoV-2 infection. CD4+ and CD8+ T cells, cytokines and HLA-G+ immune cells are associated with the natural history of the critical COVID-19 patient; however, future studies are necessary.

[Development history of acupuncture and moxibustion diagnosis and treatment institutions since the founding of the People's Republic of China].

The development process of acupuncture and moxibustion diagnosis and treatment institutions since the founding of the People's Republic of China is summarized and analyzed. The main forms of acupuncture and moxibustion diagnosis and treatment institutions have shifted from the individual, joint clinic and outpatient department of acupuncture and moxibustion in the early years of the founding of the People's Republic of China to the present acupuncture and moxibustion departments in Chinese medicine hospitals and general hospitals.The construction and development of public and private acupuncture and moxibustion hospital and key specialty of acupuncture and moxibustion fully expand the clinical application of acupuncture and moxibustion therapy. In the future, the development of acupuncture and moxibustion diagnosis and treatment institutions should highlight its own features to satisfy the requirements of different levels of society.

Correction to: Scored minor criteria for severe community-acquired pneumonia predicted better.

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Scored minor criteria for severe community-acquired pneumonia predicted better.

BACKGROUND: Infectious Disease Society of America/American Thoracic Society (IDSA/ATS) minor criteria for severe community-acquired pneumonia (CAP) are of unequal weight in predicting mortality, but the major problem associated with IDSA/ATS minor criteria might be a lack of consideration of weight in prediction in clinical practice. Would awarding different points to the presences of the minor criteria improve the accuracy of the scoring system? It is warranted to explore this intriguing hypothesis. METHODS: A total of 1230 CAP patients were recruited to a retrospective cohort study. This was tested against a prospective two-center cohort of 1749 adults with CAP. 2 points were assigned for the presence of PaO2/FiO2 ≤ 250 mmHg, confusion, or uremia on admission and 1 point for each of the others. RESULTS: The mortality rates, and sequential organ failure assessment (SOFA) and pneumonia severity index (PSI) scores increased significantly with the numbers of IDSA/ATS minor criteria present and minor criteria scores. The correlations of the minor criteria scores with the mortality rates were higher than those of the numbers of IDSA/ATS minor criteria present. As were the correlations of the minor criteria scores with SOFA and PSI scores, compared with the numbers of IDSA/ATS minor criteria present. The pattern of sensitivity, specificity, positive predictive value, and Youden's index of scored minor criteria of ≥2 scores or the presence of 2 or more IDSA/ATS minor criteria for prediction of mortality was the best in the retrospective cohort, and the former was better than the latter. The validation cohort confirmed a similar pattern. The area under the receiver operating characteristic curve of scored minor criteria was higher than that of IDSA/ATS minor criteria in the retrospective cohort, implying higher accuracy of scored version for predicting mortality. The validation cohort confirmed a similar paradigm. CONCLUSIONS: Scored minor criteria orchestrated improvements in predicting mortality and severity in patients with CAP, and scored minor criteria of ≥2 scores or the presence of 2 or more IDSA/ATS minor criteria might be more valuable cut-off value for severe CAP, which might have implications for more accurate clinical triage decisions.

Carbazole Alkaloids from Clausena anisum-olens: Isolation, Characterization, and Anti-HIV Evaluation.

Two new carbazole alkaloids (1,2) and six known carbazole alkaloids (3-8) were isolated from Clausena anisum-olens. Their structures were elucidated based on extensive spectroscopic analysis. All isolated compounds (1-8) were evaluated for their anti-HIV effects on virus replication in MT-4 lymphocytes infected by HIV-1NL4-3 Nanoluc-sec virus, and new carbazole alkaloid 1 exhibited anti-HIV activity with an EC50 value of 2.4 µg/mL and SI of 7.1.

Priority for Treatment and Intensive Care of Patients With Non-Severe Community-Acquired Pneumonia.

BACKGROUND: The Infectious Disease Society of America/the American Thoracic Society (IDSA/ATS) minor criteria for severe community-acquired pneumonia (CAP) are of unequal weight in predicting mortality. It is unclear whether the patients with non-severe CAP meeting the minor criteria most strongly associated to mortality should have the priority for treatment and intensive care. It is warranted to explore this intriguing hypothesis. METHODS: A retrospective cohort study of 1230 patients with CAP was performed. This was tested against a prospective 2-center cohort of 1749 adults with CAP. RESULTS: The patients with CAP fulfilling the predictive findings most strongly associated to mortality, i.e. PaO2/FiO2 ≤ 250 mm Hg, confusion, and uremia, showed higher mortality rates than those not fulfilling the predictive findings in subgroup analyses of the retrospective cohort. The more the number of predictive findings present, the higher the mortality rates. The prospective cohort confirmed a similar pattern. Interestingly, the patients with non-severe CAP meeting the predictive findings demonstrated unexpectedly higher mortality rates compared with the patients with severe CAP not meeting the predictive findings in the prospective cohort (P = 0.003), although there only existed death of an uptrend in the retrospective cohort. Two similar and intriguing paradigms about sequential organ failure assessment (SOFA) scores and pneumonia severity index (PSI) scores were confirmed in the 2 cohorts. CONCLUSIONS: The patients with non-severe CAP fulfilling the predictive findings most strongly associated to mortality demonstrated higher SOFA and PSI scores and mortality rates, and might have the priority for treatment and intensive care.

[Effect of Electroacupuncture at "Shenmen" (HT 7)- "Tongli" (HT 5) of Heart Meridian on Neuronal Activities in Paraventricular Nucleus of Hypothalamus in Myocardial Ischemia Rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of "Shenmen" (HT 7) - "Tongli" (HT 5) segment of the Heart Meridian on neuronal electrical activities of hypothalamic paraventricular nucleus (PVN) in rats with myocardial ischemia (MI), so as to investigate its possible mechanism underlying improvement of MI. METHODS: Thirty-two SD rats were randomly divided into sham control, model, HT 7-HT 5 and "Taiyuan" (LU 9)- "Lieque" (LU 7) groups (n=8 in each group). EA preconditioning (2 Hz, 1 V, 20 min) was applied to bilateral HT 7-HT 5 and bilateral LU 9-LU 7, respectively, once everyday for 7 days. The electrical activities of the right PVN region were recorded by the implanted microelectrode array(2×4)and Plexon multi-channel acquisition system. Cluster analysis of neuronal signals was carried out by Offline Sorter software. The discharge waveforms, autocorrelation and cross-correlation of neuronal activities were analyzed by using Neuro Explorer software. RESULTS: Cluster analysis of neuronal signals showed that 2, 2, 1 and 1 interneuron in the sham, model, HT 7-HT 5, and LU 9-LU 7 groups, and 3 pyramidal neurons in the HT 7-HT 5 were acquired. Cross correlation analysis showed that the SPK 02 a and SPK 02 b neurons of the HT 7-HT 5 group had an inhibitory relationship. The total discharge frequency was significantly increased in the model group relevant to the sham group (P<0.01), and was markedly lower in the HT 7-HT 5 group than in the model group and LU 9-LU 7 group (P<0.01). Real-time spectrum analysis showed that the local field potential spectrum energy of the HT 7-HT 5 group was significantly lower than that of the model group and the LU 9-LU 7 group. CONCLUSION: EA of HT 7-HT 5 segment of the Heart Meridian can inhibit the electrical activity of interneuron and activate the electrical activity of pyramidal neuron in PVN region, and an inhibitory relationship exists between the interneuron and pyramidal neuron in MI rats, which may be a mechanism of EA in regulating activities of the ischemic heart.

Electroacupuncture modulates the activity of the hippocampus-nucleus tractus solitarius-vagus nerve pathway to reduce myocardial ischemic injury.

The hippocampus is involved in the regulation of the autonomic nervous system, together with the hypothalamus and brainstem nuclei, such as the paraventricular nucleus and nucleus tractus solitarius. The vagus nerve-nucleus tractus solitarius pathway has an important role in cardiovascular reflex regulation. Myocardial ischemia has been shown to cause changes in the autonomic nervous system, affecting the dynamic equilibrium of the sympathetic and vagal nerves. However, it remains poorly understood how the hippocampus communicates with brainstem nuclei to regulate the autonomic nervous system and alleviate myocardial ischemic tissue damage. A rat model of acute myocardial ischemia (AMI) was made by ligating the left anterior descending branch of the coronary artery. Three days before ischemia, the hippocampal CA1 region was damaged. Then, 3 days after ischemia, electroacupuncture (EA) at Shenmen (HT7)-Tongli (HT5) was performed (continuous wave, 1 mA, 2 Hz, duration of 30 minutes). Cluster analysis of firing patterns showed that one type of neuron was found in rats in the sham and AMI groups. Three types of neurons were observed in the AMI + EA group. Six types of neurons were found in the AMI + EA + Lesion group. Correlation analysis showed that the frequency of vagus nerve discharge in each group was negatively correlated with heart rate (HR) (P < 0.05, r = -0.424), and positively correlated with mean arterial pressure (MAP) (P < 0.05, r = 0.40987) and the rate-pressure product (RPP) (P < 0.05, r = 0.4252). The total frequency of the nucleus tractus solitarius discharge in each group was positively correlated with vagus nerve discharge (P < 0.01, r = 0.7021), but not with hemodynamic index (HR: P > 0.05, r = -0.03263; MAP: P > 0.05, r = -0.08993; RPP: P > 0.05, r = -0.03263). Some neurons (Neuron C) were negatively correlated with vagus nerve discharge, HR, MAP and RPP in the AMI + EA group (vagus nerve discharge: P < 0.05, r = -0.87749; HR: P < 0.01, r = -0.91902; MAP: P < 0.05, r = -0.85691; RPP: P < 0.01, r = -0.91902). Some neurons (Neurons C, D and E) were positively correlated with vagus nerve discharge, HR, MAP and RPP in the AMI + EA + Lesion group (vagus nerve discharge: P < 0.01, r = 0.8905, P < 0.01, r = 0.9725, P < 0.01, r = 0.9054; HR: P < 0.01, r = 0.9347, P < 0.01, r = 0.9089, P < 0.05, r = 0.8247; MAP: P < 0.05, r = 0.8474, P < 0.01, r = 0.9691, P < 0.01, r = 0.9027; RPP: P < 0.05, r = 0.8637, P < 0.01, r = 0.9407, P < 0.01, r = 0.9027). These findings show that the hippocampus-nucleus tractus solitarius-vagus nerve pathway is involved in the cardioprotective effect of EA at the heart meridian. Some interneurons in the nucleus tractus solitarius may play a particularly important role in the cardiomodulatory process.