19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Objective To investigate the effect of elastic pants on coagulation function and deep vein thrombosis by examining blood coagulation function and deep vein thrombosis in patients with liposuction in the thigh before and after operation.Methods 80 patients with liposuction were randomly divided into Ankle-length elastic pants(Ankle group,A group,n=40)and Knee-length elastic pants(Knee group,K group,n=40)from October 2021 to October 2022.After liposuction surgery,the two groups of patients used elastic bandage to initially compress and bind the thigh.According to the length of the patients'thigh,the patients in A group wore appropriate ankle-length elastic pants and the patients in K group wore appropriate knee-length elastic pants.The index were recorded including the popliteal vein flow rate,the common femoral vein flow rate,the instep temperature,the incidence of deep vein thrombosis(DVT),the incidence of intramuscular vein thrombosis of leg and the coagulation indexes(APTT,PT,Fib,D-dimer).Results Compared with pre-operation,the blood flow rate of popliteal vein and common femoral vein in A group was significantly faster,while the blood flow rate of popliteal vein in K group was significantly slower(P＜0.05).There was no significant change in APTT and PT in the two groups after operation(P＞0.05),but the Fib and D-Dimer increased significantly on the first day after operation,and then decreased gradually(P＜0.05).Compared with K group,the blood flow of popliteal vein and common femoral vein in A group was significantly faster at each time point after operation(P＜0.05).The Fib and D-Dimer of patients in A group were significantly lower than those in K group on the 1st,3rd and 7th day after operation(P＜0.05),and the blood coagulation index between the two groups returned to normal around the 14th day.There was no statistically significant difference in the instep temperature between groups and within groups(P＞0.05).No deep venous thrombosis was found in A group after surgery,while there were 3 cases of deep venous thrombosis without clinical symptoms in K group on the 3rd and 7th day,with no statistical difference(P＞0.05).After surgery,patients in A group and K group had intramuscular venous thrombosis of the leg on the 1st,3rd and 7th day after surgery,and there was statistically significant difference on the 3rd and 7th day between the two groups(P＜0.05).Conclusion Thigh liposuction can lead to deep vein thrombosis without obvious clinical symptoms and intramuscular vein thrombosis of leg.Ankle-length elastic pants are more conducive to blood circulation of patients'legs,improve blood hypercoagulability,and reduce the risk of deep vein thrombosis after operation.

【Objective】 To explore the relationship between the storage time of leukodepleted red blood cells and transfusion adverse reactions by analyzing the occurrence of transfusion adverse reactions of patients after leukodepleted red blood cells transfusion from four hospitals. 【Methods】 By using the electronic medical record management system, the collection and transfusion dates of leukodepleted red blood cells from four hospitals in Enshi Prefecture from 2018 to 2022, as well as the information on transfusion adverse reactions, were retrieved. 【Results】 From 2018 to 2022, a total of 697 61 bags of leukodepleted red blood cells were transfused in four hospitals, resulting in 166 cases of transfusion adverse reactions, among which 93 were allergic reactions, 63 were non hemolytic febrile reactions, and 10 were others, with a total incidence rate of transfusion adverse reactions at 0.24%. The average storage time of leukodepleted red blood cells with and without transfusion adverse reactions was (20.25±6.31) and (19.88±5.50) days, respectively. With a storage time of 7 days as the threshold, the incidence of transfusion adverse reactions was the lowest for a storage time of 15~21 days. The incidence of transfusion adverse reactions of leukodepleted red blood cells in two groups (with storage days ≤21 days and >21 days) was not statistically significant(P>0.05). 【Conclusion】 Allergic reactions were the main type of transfusion adverse reaction caused by leukodepleted red blood cells, and the incidence of transfusion adverse reactions decreased and then increased with the prolongation of the storage time of leukodepleted red blood cells. There was no significant difference in the incidence of transfusion adverse reactions with leukodepleted red blood cells stored for ≤ 21 days and >21 days.

OBJECTIVE: To examine the anti-inflammatory effects and potential mechanisms of polypeptide from Moschus (PPM) in lipopolysaccharide (LPS)-induced THP-1 macrophages and BALB/c mice. METHODS: The polypeptide was extracted from Moschus and analyzed by high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Subsequently, LPS was used to induce inflammation in THP-1 macrophages and BALB/c mice. In LPS-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and lactate dehydrogenase release assays; the proinflammatory cytokines and reactive oxygen species (ROS) were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively; and protein and mRNA levels were measured by Western blot and real-time quantitative polymerase chain reaction (qRT-PCR), respectively. In LPS-induced BALB/c mice, the proinflammatory cytokines were measured, and lung histology and cytokines were observed by hematoxylin and eosin (HE) and immunohistochemical (IHC) staining, respectively. RESULTS: The SDS-PAGE results suggested that the molecular weight of purified PPM was in the range of 10-26 kD. In vitro, PPM reduced the production of interleukin 1β (IL-1β), IL-18, tumor necrosis factor α (TNF-α), IL-6 and ROS in LPS-induced THP-1 macrophages (P<0.01). Western blot analysis demonstrated that PPM inhibited LPS-induced nuclear factor κB (NF-κB) pathway and thioredoxin interacting protein (TXNIP)/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3) inflammasome pathway by reducing protein expression of phospho-NF-κB p65, phospho-inhibitors of NF-κB (Iκ Bs) kinase α/β (IKKα/β), TXNIP, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1 (P<0.05 or P<0.01). In addition, qRT-PCR revealed the inhibitory effects of PPM on the mRNA levels of TXNIP, NLRP3, ASC, and caspase-1 (P<0.05 or P<0.01). Furthermore, in LPS-induced BALB/c mice, PPM reduced TNF-α and IL-6 levels in serum (P<0.05 or P<0.01), decreased IL-1β and IL-18 levels in the lungs (P<0.01) and alleviated pathological injury to the lungs. CONCLUSION PPM could attenuate LPS-induced inflammation by inhibiting the NF-κB-ROS/NLRP3 pathway, and may be a novel potential candidate drug for treating inflammation and inflammation-related diseases.

Autoantibodies ; COVID-19 ; Humans ; Singapore/epidemiology*

Yi Yin, a famous medical scientist and culinary master in the late Xia Dynasty and early Shang Dynasty, developed the Chinese medicinal liquids and Chinese medicinal prescriptions emerged after that. Chinese medicinal prescriptions have attracted much attention because of their unique advantages in the treatment of chronic multifactorial diseases, representing an important direction of drug discovery in the future. Yiyin decoction theory is the superior form of personalized combined medication with advanced consciousness. It is different from not only the magic bullet theory of single component action but also the connotation of modern multi-target drugs. The core of Yiyin decoction theory can be summarized as compound compatibility, multiple effects, and moderate regulation. Compound compatibility refers to that the formulation of Chinese medicinal prescriptions involves the complex synergy and interactions between sovereign, minister, assistant, and guide medicinal materials. Multiple effects mean that the prescriptions employ a variety of mechanisms to exert comprehensive pharmacological effects of nonlinear feedback. Moderate regulation reflects that the prescriptions can accurately regulate the multiple points of the disease biological network as a whole. To solve the mystery of Yiyin decoction theory, we should not only simply study the known active substances(components) and their independent target effects in the mixture, but also mine the "dark matter" and "dark effect" of Chinese medicinal prescriptions. That is, we should learn the neglected atypical pharmacological effects of Chinese medicinal prescriptions and the multi-point nesting mechanism that plays a precise regulatory function in the body. Yiyin decoction theory focuses on the overall pharmacological effect to reflect the comprehensive clinical value of Chinese medicinal prescriptions, which is of great significance for the development of a new model for the evaluation and application of new Chinese medicinal prescriptions in line with the theory of traditional Chinese medicine.
China ; Drugs, Chinese Herbal/pharmacology* ; Medicine, Chinese Traditional ; Prescriptions

Objective:To review and summarize the main problems that have occurred in the history of manned spaceflight worldwide and the experience of the medical rescue support for astronauts at the main landing site since the first manned spaceflight mission of the Shenzhou-5 in China in 2003, focus on the technical status and return characteristics during the construction of the space station since the Shenzhou-12, and formulate a targeted injury treatment plan to ensure the safety of astronauts.Methods:This article summarized the lessons of accidental injuries of astronauts in foreign aerospace history, especially in the space station stage, combined with the experience of medical support of astronauts in manned spaceflight in China, and put forward a series of organizations, plans and treatments according to the mission characteristics of long-term orbits and adjustments of the main landing sites of space station mission spacecraft.Results:On the basis of the original pre-cabin emergency and helicopter ICU comprehensive rescue platform, the emergency procedures were further optimized, and the treatment plans under different complex terrains and the principles of rapid treatment and evacuation of astronauts were formulated.Conclusions:The effective treatment of astronauts returning from the space station in various situations could be ensured by the comprehensive rescue plan for the medical rescue of the space station mission and the construction and organization of the helicopter rescue platform.

Objective:This study aims to analyze the characteristics and basic principles of emergency surgery risks and anesthesia care of medical support at the landing site for China’s taikonauts of the Shenzhou-12, and to summarize China’s experience in medical support at the landing site for manned spaceflight, and ensure supports in special environments such as an emergency return of manned spaceflight.Methods:This study was carried out through literature research on relevant reports on the emergency surgery risks and aids of domestic and foreign astronauts at the landing sites, and summaries of the experience in medical support for taikonauts of spacecrafts from Shenzhou-5 to Shenzhou-11 at the landing sites. At the same time, according to the characteristics of Shenzhou-12 such as the long on-orbit time, the adjustment in the landing area, the optimization of the mission mode, and new search and rescue power, a series of organization, pre-arranged planning, equipment allocation, and effective anesthesia treatment plan were proposed and inspected in practice.Results:Based on the original anesthesia care plan of medical support, the first-aid carrier was adjusted and modified, the first-aid procedure was optimized, a new generation of supraglottic airway opening tool, video laryngoscope, portable ultrasound, and other devices were added, and the anesthesia care plan at the landing site for manned spaceflight was formulated to provide strong support for the medical care of taikonauts that had stayed in the outer space for a long time.Conclusions:Upon the targeted improvement and process optimization, the anesthesia care plan of medical support for taikonauts of Shenzhen-12 in the landing area fully meets the anesthesia requirement of medical support in special environments such as the emergency return of the taikonauts that have stayed in the outer space for a long time under the new orbital altitude.

This study aimed to investigate the effect of Tibetan medicine Ershiwuwei Songshi Pills(ESP) on the intestinal flora of non-alcoholic steatohepatitis(NASH) mice. Forty-eight male C57 BL/6 mice were randomly divided into the control group, model(methionine-choline-deficient, MCD) group, high-(0.8 g·kg~(-1)), medium-(0.4 g·kg~(-1)), and low-dose(0.2 g·kg~(-1)) ESP groups, and pioglitazone(PGZ, 10 mg·kg~(-1)) group, with eight mice in each group. Mice in the control group were fed with normal diet, while those in the remaining five groups with MCD diet for five weeks for inducing NASH. During modeling, they were gavaged with the corresponding drugs. The changes in body mass, daily water intake, and daily food intake were recorded. At the end of the experiment, the liver tissues were collected and stained with hematoxylin-eosin(HE) for observing the pathological changes, followed by oil red O staining for observing fat accumulation in the liver. The levels of serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) and triglyceride(TG) in liver tissue were measured. The changes in intestinal flora of mice were determined using 16 S rRNA high-throughput sequencing technology. The results showed that compared with the model group, the high-, medium-and low-dose ESP groups and the PGZ group exhibited significantly lowered AST and ALT in serum and TG in liver tissues and alleviated hepatocellular steatosis and fat accumulation in the liver. As demonstrated by 16 S rRNA sequencing, the abundance index and diversity of intestinal flora decreased in the model group, while those increased in the ESP groups. Besides, the Firmicutes to Bacteroidetes ratio decreased at the phylum level. In the alteration of the composition of intestinal flora, ESP reduced the abundance of Erysipelotrichia and Faecalibaculum but increased the abundance of Desulfovibrionaceae, Rikenellaceae, Lachnospiraceae, and Ruminococcaceae. This study has revealed that ESP has a protective effect against NASH induced by MCD diet, which may be related to its regulation of the changes in intestinal flora, alteration of the composition of intestinal flora, and inhibition of the intestinal dysbiosis.
Animals ; Disease Models, Animal ; Gastrointestinal Microbiome ; Liver ; Male ; Medicine, Tibetan Traditional ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/drug therapy*

A chronic cholestasis model was induced in mice by feeding a diet containing 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine(DDC). The effects of Ershiwuwei Songshi Pills(ESP) on endogenous metabolites in mice with chronic cholestasis were investigated by metabolomics analysis based on liquid chromatography-mass spectrometry(LC-MS). The results showed that ESP was effective in improving pathological injury and reducing serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP), and total bile acid in the model mice. Meanwhile, 13 common differential metabolites were revealed in metabolomic screening between the model/control group and the model/ESP group, including uric acid, glycolaldehyde, kynurenine, flavin adenine dinucleotide, L-3-phenyllactic acid, I-urobilin, leukotriene D4(LTD4), taurocholic acid, trioxilin A3, D-inositol-1,4-diphosphate, PC [16:0/20:2(11Z,14Z)], PC[14:0/22:2(13Z,16Z)], and PC[20:4(5Z,8Z,11Z,14Z)/20:4(5Z,8Z,11Z,14Z)]. After ESP intervention, the levels of all 13 differential metabolites were significantly retraced, and pathway analysis showed that ESP achieved its therapeutic effect mainly by affecting arachidonic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism, and primary bile acid biosynthesis. This study elucidated the mechanism of action of ESP against chronic cholestasis based on metabolites.
Animals ; Bile Acids and Salts ; Cholestasis/drug therapy* ; Chromatography, Liquid ; Medicine, Tibetan Traditional ; Metabolomics ; Mice