Gut microbiota, circulating cytokines and dementia: a Mendelian randomization study.

BACKGROUND: Some studies have shown that gut microbiota may be associated with dementia. However, the causal effects between gut microbiota and different types of dementia and whether cytokines act as a mediator remain unclear. METHODS: Gut microbiota, cytokines, and five dementia types, including Alzheimer's disease (AD), frontotemporal dementia (FTD), dementia with Lewy body (DLB), vascular dementia (VD), and Parkinson's disease dementia (PDD) were identified from large-scale genome-wide association studies (GWAS) summary data. We used Mendelian randomization (MR) to investigate the causal relationships between gut microbiota, cytokines, and five types of dementia. Inverse variance weighting (IVW) was used as the main statistical method. In addition, we explored whether cytokines act as a mediating factor in the pathway from gut microbiota to dementia. RESULTS: There were 20 positive and 16 negative causal effects between genetic liability in the gut microbiota and dementia. Also, there were five positive and four negative causal effects between cytokines and dementias. Cytokines did not act as mediating factors. CONCLUSIONS: Gut microbiota and cytokines were causally associated with five types of dementia, and cytokines seemed not to be the mediating factors in the pathway from gut microbiota to dementia.

[Correlation Between Initial Postoperative Hemoglobin Value and Prognosis in Non-Cardiac Surgery Patients Receiving Intraoperative Blood Transfusion].

Objective: To analyze the relationship between initial (within 24 hours) postoperative hemoglobin (Hb) value and prognosis in non-cardiac surgery patients receiving intraoperative blood transfusion, and to provide support for sensible blood use in surgery. Methods: A retrospective analysis was performed on all patients aged 18 or older who underwent non-cardiac surgeries and who received intraoperative blood transfusion at West China Hospital, Sichuan University from 2012 to 2018. According to their initial postoperative Hb levels, the patients were divided into 6 groups, including Hb<75 g/L, 75 g/L≤Hb<85 g/L, 85 g/L≤Hb<95 g/L, 95 g/L≤Hb<105 g/L, 105 g/L≤Hb<115 g/L, and Hb≥115 g/L goups. Multivariate linear regression was performed to examine the differences in the length-of-stay between the groups and binary logistic regression analysis was conducted to examine the differences between the groups in inpatient mortality, the rate of patient voluntary discharge against medical advice, incidence of acute ischemic injury, including acute kidney injury, myocardial infarction, and cerebral infarction, and length-of-stay longer than 28 days. In addition, the effects of multiple interactions between initial postoperative Hb and the types of surgery, the amount of intraoperative red blood cell infusion (red blood cell<8 U vs. red blood cell≥8 U), and preoperative anemia status (Hb<100 g/L vs. Hb≥100 g/L) on postoperative length-of-stay were analyzed. Results: A total of 7528 patients were included in this study. Compared to those of the reference group, the 95 g/L≤Hb<105 g/L group, the length-of-stay of patients with initial postoperative Hb<75 g/L increased and the mortality (odds ratio [ OR]=2.562) and the rate of voluntary discharge against medical advice ( OR=1.681) increased significantly. Patients in the 75 g/L≤Hb<85 g/L group had increased length-of-stay and increased incidence of acute ischemic injury ( OR=1.778) relative to the reference group. The interaction analysis showed that there was significant interaction between initial postoperative Hb and the types of surgery, which influenced the postoperative length-of-stay. Conclusion: In non-cardiac surgery patients who have receive blood transfusion, initial postoperative Hb<85 g/L is associated with poorer prognosis. However, those patients with higher initial postoperative Hb did not gain more benefits, suggesting that 85 g/L≤Hb<95 g/L may be the target Hb value for sensible intraoperative transfusion.

A Laser Line Auto-Scanning System for Underwater 3D Reconstruction.

In this study, a laser line auto-scanning system was designed to perform underwater close-range 3D reconstructions with high accuracy and resolution. The system changes the laser plane direction with a galvanometer to perform automatic scanning and obtain continuous laser strips for underwater 3D reconstruction. The system parameters were calibrated with the homography constraints between the target plane and image plane. A cost function was defined to optimize the galvanometer's rotating axis equation. Compensation was carried out for the refraction of the incident and emitted light at the interface. The accuracy and the spatial measurement capability of the system were tested and analyzed with standard balls under laboratory underwater conditions, and the 3D surface reconstruction for a sealing cover of an underwater instrument was proved to be satisfactory.

Application of Microfluidics in Drug Development from Traditional Medicine.

While there are many clinical drugs for prophylaxis and treatment, the search for those with low or no risk of side effects for the control of infectious and non-infectious diseases is a dilemma that cannot be solved by today's traditional drug development strategies. The need for new drug development strategies is becoming increasingly important, and the development of new drugs from traditional medicines is the most promising strategy. Many valuable clinical drugs have been developed based on traditional medicine, including drugs with single active ingredients similar to modern drugs and those developed from improved formulations of traditional drugs. However, the problems of traditional isolation and purification and drug screening methods should be addressed for successful drug development from traditional medicine. Advances in microfluidics have not only contributed significantly to classical drug development but have also solved many of the thorny problems of new strategies for developing new drugs from traditional drugs. In this review, we provide an overview of advanced microfluidics and its applications in drug development (drug compound synthesis, drug screening, drug delivery, and drug carrier fabrication) with a focus on its applications in conventional medicine, including the separation and purification of target components in complex samples and screening of active ingredients of conventional drugs. We hope that our review gives better insight into the potential of traditional medicine and the critical role of microfluidics in the drug development process. In addition, the emergence of new ideas and applications will bring about further advances in the field of drug development.

The Preventive Value of Acupoint Sensitization for Patients with Stable Angina Pectoris: A Randomized, Double-Blind, Positive-Controlled, Multicentre Trial.

BACKGROUND: Acupoint sensitization is considered an important factor in the efficacy of acupoint therapy. This study aimed to evaluate the efficacy of acupressure in the prevention of stable angina pectoris using acupoints with different pressure-pain sensitivities. METHODS: A total of 202 patients were enrolled and randomly assigned to a high-sensitivity group (HSG) (n = 109) in which patients received acupressure at the five acupoints with the highest sensitivity to pain and a low-sensitivity group (LSG) (n = 93) in which patients received acupressure at the five acupoints with the lowest sensitivity to pain. The duration of acupressure treatment was 4 weeks, and the patients were evaluated at baseline, week 4, and week 8. The primary outcome was a change in the frequency of angina attacks from baseline. The secondary outcomes included nitroglycerin consumption, the Canadian Cardiovascular Society classification, and the Seattle Angina Questionnaire score. Adverse events such as bleeding and subcutaneous haemorrhage were recorded in both groups. RESULTS: The effect of acupressure compared with baseline on the prevention of angina pectoris in HSG was better than that in LSG at week 4 (incidence rate ratio (IRR): 0.691 and 95% confidence interval (CI): [0.569, 0.839]) and week 8 (IRR: 0.692 and 95% CI: [0.569, 0.839]). No significant difference between groups was found in the frequency of nitroglycerin consumption at week 4 (odds ratio (OR) = 0.863 and 95% CI: [0.147, 5.077]) or week 8 (OR = 1.426 and 95% CI: [0.211, 9.661]). Two themes in the questionnaire showed significantly different changes from baseline between the two groups. Scores on the angina frequency (AF) subscale had changed more from the baseline in the HSG at week 8 than in the LSG (mean difference (MD) = 3.807 and 95% CI: [0.673, 6.942]). Scores on the treatment satisfaction (TS) subscale had also changed more in the HSG than in the LSG at week 4 (MD = 3.651 and 95% CI: [0.327, 7.327]) and week 8 (MD = 4.220 and 95% CI: [0.347, 7.346]). One patient in the LSG reported bruising at the acupoint. No unexpected safety problems arose. CONCLUSIONS: This study showed that acupressure at acupoints with high sensitivity to pain may effectively reduce the frequency of stable angina pectoris episodes. This trial is registered with NCT03975140.

Nitrogen fertilizer at heading stage effectively compensates for the deterioration of rice quality by affecting the starch-related properties under elevated temperatures.

Relevant evidence of rice quality responses to increased temperatures under field condition has been obtained in our previous study. Understanding the intrinsic mechanism of increased temperatures and fertilizer treatment in regulating rice quality formation will be contributed to the development of mitigation measures suitable for actual field operations and to cope with climate warming. This study investigated the potential role of nitrogen fertilizer in regulating the rice quality under field warming through identifying starch-related property indicators. Results showed application of nitrogen fertilizer at heading stage effectively delayed the significantly increased accumulation of total starch, amylose and amylopectin, and reduced the starch particle size, chain length distribution, and crystal structure induced by high temperature, which further compensated the deterioration of rice quality caused by elevated temperature.

Exogenous spermidine enhances the photosynthetic and antioxidant capacity of rice under heat stress during early grain-filling period.

High temperature has adverse effects on rice growth by inhibiting the flag leaf photosynthetic and antioxidant capacity, which can be alleviated by various exogenous chemicals such as spermidine (Spd). However, the role of Spd in conferring heat tolerance in rice is not well documented. Conventional japonica rice varieties Wuyunjing 24 and Ningjing 3 were treated with high temperatures at 37.5/27.0°C (day/night) and foliar sprayed with 1mmolL-1 Spd after flowering. Results showed activities of superoxide dismutase (SOD) and peroxidase (POD) activities were deceased during high temperature treatment and eventually lead to the malondialdehyde (MDA) accumulation. Exogenous Spd significantly increased both SOD and POD activities at the later stage of high-temperature treatment, and reduced MDA accumulation were identified in both rice varieties. Application of Spd further increased the amount of soluble sugars during high temperature stress and that maintained the osmotic equilibrium of rice leaves. Spd significantly increased photosystem II (ΦPSII), photosynthetic electron transport rate (ETR), variable fluorescence/maximum fluorescence ratio (Fv'/Fm'), stomatal conductance and the photochemical reaction of light energy ratio (Pr), and ultimately improved the photosynthetic and transpiration rate during high temperature stress. In conclusion, exogenous Spd can effectively alleviate the adverse consequences of high temperature and could be further applied to provide strategies in mitigating the challenges of global warming-induced yield loss and other possible relevant issues.

Chemosensitizing effect of Paris Saponin I on Camptothecin and 10-hydroxycamptothecin in lung cancer cells via p38 MAPK, ERK, and Akt signaling pathways.

Paris Saponin I (PSI), a steroidal sponins isolated from plant, has been exhibited antitumor and many other biological activities. In this study, we investigated the role and underlying mechanisms of PSI in the synergistic regulation of antitumor activity of Camptothecin (CPT) and 10-hydroxycamptothecin (HCPT) in four types of lung cancer cells. The inhibitory evaluation showed that PSI could significantly reduce the CPT/HCPT-mediated cell proliferation and enhance the sensitivities of H1299, H460 and H446 lung cancer cells to CPT/HCPT. Mechanism study indicated that PSI improved the CPT/HCPT induced apoptosis in lung cancer cells through mitochondria pathway including cytochrome C release and activation of caspase-9 and -3 cascades. Furthermore, PSI plus CPT/HCPT also increased the up-regulation of Bax and down-regulation of Bcl-2 and Bcl-XL in H460 and H446 cells. Moreover, PSI enhanced CPT/HCPT-mediated inhibition of p38 MAPK and activation of phosphorylation of p38 MAPK in H1299 cells, and suppression of Akt and ERK pathways activation in H460 cells as well as in H446 cells. Collectively, our results demonstrated that PSI functions as a chemosensitizer by enhancing apoptosis through influencing p38 MAPK, ERK, and Akt pathways in lung cancer cells, and the combination with CPT/HCPT might be a promising strategy for the development of new therapeutic agents.