ObjectiveObesity has been identified as one of the most important risk factors for cognitive dysfunction. Physical exercise can ameliorate learning and memory deficits by reversing synaptic plasticity in the hippocampus and cortex in diseases such as Alzheimer’s disease. In this study, we aimed to determine whether 8 weeks of treadmill exercise could alleviate hippocampus-dependent memory impairment in high-fat diet-induced obese mice and investigate the potential mechanisms involved. MethodsA total of sixty 6-week-old male C57BL/6 mice, weighing between 20-30 g, were randomly assigned to 3 distinct groups, each consisting of 20 mice. The groups were designated as follows: control (CON), high-fat diet (HFD), and high-fat diet with exercise (HFD-Ex). Prior to the initiation of the treadmill exercise protocol, the HFD and HFD-Ex groups were fed a high-fat diet (60% fat by kcal) for 20 weeks. The mice in the HFD-Ex group underwent treadmill exercise at a speed of 8 m/min for the first 10 min, followed by 12 m/min for the subsequent 50 min, totally 60 min of exercise at a 0° slope, 5 d per week, for 8 weeks. We employed Y-maze and novel object recognition tests to assess hippocampus-dependent memory and utilized immunofluorescence, Western blot, Golgi staining, and ELISA to analyze axon length, dendritic complexity, number of spines, the expression of c-fos, doublecortin (DCX), postsynaptic density-95 (PSD95), synaptophysin (Syn), interleukin-1β (IL-1β), and the number of major histocompatibility complex II (MHC-II) positive cells. ResultsMice with HFD-induced obesity exhibit hippocampus-dependent memory impairment, and treadmill exercise can prevent memory decline in these mice. The expression of DCX was significantly decreased in the HFD-induced obese mice compared to the control group (P<0.001). Treadmill exercise increased the expression of c-fos (P<0.001) and DCX (P=0.001) in the hippocampus of the HFD-induced obese mice. The axon length (P<0.001), dendritic complexity (P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P<0.001) in the hippocampus were significantly decreased in the HFD-induced obese mice compared to the control group. Treadmill exercise increased the axon length (P=0.002), dendritic complexity(P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P=0.001) of the hippocampus in the HFD-induced obese mice. Our study found a significant increase in MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of HFD-induced obese mice compared to the control group. Treadmill exercise was found to reduce the number of MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of obese mice induced by a HFD. ConclusionTreadmill exercise led to enhanced neurogenesis and neuroplasticity by increasing the axon length, dendritic complexity, dendritic spine numbers, and the expression of PSD95 and DCX, decreasing the number of MHC-II positive cells and neuroinflammation in HFD-induced obese mice. Therefore, we speculate that exercise may serve as a non-pharmacologic method that protects against HFD-induced hippocampus-dependent memory dysfunction by enhancing neuroplasticity and neurogenesis in the hippocampus of obese mice.

Rheumatoid arthritis (RA) is an autoimmune disease driven by antigens and mediated by T cells. Collagen II (CII) and fibrinogen (Fib) are the two main antigens in the pathogenesis of RA. The antigen produced after citrulline modification (Cit) is also one of the inducements to induce the body to produce a pathogenic anti-citrulline protein antibody (ACPA). To provide a reference for RA-related research, this study intends to establish an RA animal model by using CII, Cit-CII, Fib, and Cit-Fib antigens, emulsification with complete Freund's adjuvant and immunization with DBA/1 mice, respectively, to compare the pathological characteristics of RA models induced by different antigens from the aspects of pathology, imaging and serum biochemistry. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of the China Academy of Chinese Medical Sciences. The results showed that the CII, Cit-CII, and Cit-Fib induced mice all had symptoms such as joint redness and swelling, and toe deformation and the clinical score and incidence rate were higher than those of the normal group. The CII group had the most serious lesions, with a incidence rate of 100%, and the Cit-CII and Cit-Fib groups had mild symptoms, with a incidence rate of 25% and 37.5%, respectively; pathological and imaging examination results showed that the joints of mice in CII-induced group showed severe synovial inflammation, cartilage and bone destruction, while those in Cit-CII and Cit-Fib group showed only slight inflammatory infiltration, joint cavity stenosis and bone destruction; the results of serum antibody detection showed that CII, Cit-CII and Cit-Fib groups all produced high levels of anti-cyclic citrullinated peptide (CCP) antibodies, among which, Cit-Fib group > Cit-CII group > CII group > Fib group, and both Cit-CII and Cit-Fib groups produced high levels of citrullinated epitope-specific antibodies, while the total IgG level was the highest in CII group; serum ELISA and RT-PCR analysis of joint tissue showed that the expression of pro-inflammatory factors and bone destruction-related molecules increased most significantly in the CII-induced group, followed by Cit-Fib and Cit-CII. The above results showed that among the four different antigens, the symptoms and conditions of arthritis in RA mice induced by CII were the most serious, and IgG instead of anti-CCP antibody was its typical immunological feature, and CII could be the first choice for the model of RA mice; Cit-Fib has certain immunogenicity, can partially induce the symptoms and conditions of RA arthritis in mice, and produce high-level anti-CCP antibody and anti-Cit-Fib antibody, which is more suitable for the study of citrulline-related RA; although Cit-CII has certain immunogenicity, the incidence, and severity of RA arthritis induced by Cit-CII in mice are low.

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
Humans ; Consensus ; Critical Care/methods* ; Intensive Care Units ; Pain/drug therapy* ; Analgesics/therapeutic use* ; Delirium/therapy* ; Critical Illness

Intestinal flora dysbiosis may play an important role in the occurrence and development of chronic fatigue syndrome (CFS), which may induce the inflammatory response and metabolic disturbance of patients with CFS. Acupuncture and moxibustion may achieve anti-fatigue effect by affecting the diversity and quantity of intestinal flora, improving intestinal barrier function, and regulating brain-gut peptides.
Acupuncture Therapy ; Fatigue Syndrome, Chronic/therapy* ; Gastrointestinal Microbiome ; Humans ; Moxibustion

Critical ultrasonography is widely used in ICU and has become an indispensable tool for clinicians. However, besides operator-dependency of critical ultrasonography, lack of standardized training mainly result in the physicians′ heterogenous ultrasonic skill. Therefore, standardized training as well as strict quality control plays the key role in the development of critical ultrasonography. We present this quality control standards to promote better development of critical ultrasonography.

Objective: To investigate the effect of maternal exposure to lipopolysaccharide during pregnancy on allergic asthma in offspring in mice. Methods: Animal experimental research was carried out from June 2019 to June 2021.Pregnant C57BL/6J mice were randomly divided into 2 groups by intraperitoneal injection with 7 μg/kg lipopolysaccharide (LPS) or phosphate buffered saline (PBS) at day 15.5 of gestation. After birth, 6 offspring were randomly chosen from each group at the age of 4 weeks, and stimulated with house dust mites (HDM) or PBS, further divided into 4 groups, such as LPS+PBS group, LPS+HDM group, PBS+PBS group, PBS+HDM group, with 3 mice in each group. The cough and wheezing were observed, the histological changes in lung tissue were examined after HE staining, and the expression of inflammatory factors including interleukin (IL)-4, IL-6, IL-17A, IL-23, interferon (IFN)-α and IFN-β in the lung tissue were detected by high-throughput liquid protein chip detection. T test or rank sum test was used for the comparison among these groups. Results: The asthma-like airway inflammation was more obvious in PBS+HDM group after stimulated by HDM than that in PBS+PBS group, nevertheless, this manifestation in LPS+HDM group was milder than that in PBS+HDM group. HE staining showed that inflammatory cell aggregation in the lung tissue in PBS+HDM group was significantly higher than that in PBS+PBS group (4.0 (3.5, 4.0) vs. 0 (0, 0.5), Z=2.02, P=0.043), while it was much lower in LPS+HDM group compared to PBS+HDM group (1.0 (0.5, 1.5) vs. 4.0 (3.5, 4.0), Z=1.99, P=0.046). High-throughput liquid protein chip detection of lung tissue showed that IL-6, IL-23 and IFN-β levels were significantly higher in PBS+HDM group when compared to those in PBS+PBS group ((114±3) vs. (94±4) ng/L, (210±4) vs. (173±7) ng/L, (113±2) vs. (94±4) ng/L, t=4.37, 4.84, 3.96, all P<0.05), while the levels of IL-6, IL-23, IFN-α, IFN-β in LPS+HDM group were significantly lower than those in PBS+HDM group ((87±5) vs. (114±3) ng/L, (171±7) vs. (210±4) ng/L, (16.1±0.6) vs. (20.9±0.3) ng/L, (95±1) vs. (113±2) ng/L, t=5.07, 5.07, 7.28, 7.47, all P<0.05). Conclusions: Prenatal low dose LPS exposure can reduce offspring's airway inflammatory reactions and prevent the development of allergic disease. Maternal infection during pregnancy may affect the occurrence and development of allergic asthma in offspring.
Animals ; Asthma/etiology* ; Disease Models, Animal ; Female ; Humans ; Inflammation ; Interleukin-23 ; Interleukin-6 ; Lipopolysaccharides ; Lung ; Maternal Exposure/adverse effects* ; Mice ; Mice, Inbred C57BL ; Pregnancy ; Pyroglyphidae

Obstructive sleep apnea hypopnea syndrome(OSAHS)is a group of diseases which occurred in the upper respiratory tract with transient, recurrent, partial or complete obstruction during night sleep. It can affect the regulation of hemodynamics, endocrine systems and autonomic nerve, and then result in the reduction of body oxygen saturation, chronic hypoxia and hypercapnia. Beside being an independent risk factor for cardiovascular and cerebrovascular diseases, many studies have shown that it is also associated with ocular surface diseases in OSAHS, such as floppy eyelid syndrome, dry eye, keratoconus, etc., but there is still a lack of perfect systematic analysis. This paper reviews the relationship between OSAHS and relevant ocular surface diseases including pathogenesis,clinical manifestations and treatment progress, in order to reduce the ophthalmic complications of OSAHS patients in clinical diagnosis and treatment,and better improve the quality of life of patients.

Bombesin receptor subtype-3(BRS-3) is an orphan receptor in the bombesin receptor family. Its signal transduction mechanism and biological function have attracted much attention. Seeking the ligand for BRS-3 is of great significance for exploring its function. Considering the fact that the activation of BRS-3 receptor can induce the change in intracellular Ca~(2+) concentration, the fluo-rometric imaging plate reader(FLIPR) was utilized for ligand screening at the cellular level. Among more than 400 monomeric compounds isolated from Chinese herbs, yuanhunine from Corydalis Rhizoma and sophoraisoflavanone A and licoriphenone from Glycyrrhizae Radix et Rhizoma antagonized BRS-3 to varying degrees. It was confirmed in HEK293 cells expressing BRS-3 that yuanhunine, sophoraisoflavanone A, and licoriphenone inhibited the calcium current response after the activation of BRS-3 by [D-Phe~6,β-Ala~(11),Phe~(13),Nle~(14)]bombesin-(6-14) in a dose-dependent manner with the IC_(50) values being 8.58, 4.10, and 2.04 μmol·L~(-1), respectively. Further study indicated that yuanhunine and sophoraisoflavanone A exhibited good selectivity for BRS-3. In this study, it was found for the first time that monomers derived from Chinese herbs had antagonistic activity against orphan receptor BRS-3, which has provided a tool for further study of BRS-3 and also the potential lead compounds for new drug discovery. At the same time, it provides reference for the research and development of innovative drugs based on the active ingredients of Chinese herbs.
Drugs, Chinese Herbal/chemistry* ; HEK293 Cells ; Humans ; Ligands ; Receptors, Bombesin

Endoscopy ; Humans ; Neoplasms/surgery* ; Submandibular Gland/surgery* ; Thyroidectomy

Acute ischemic stroke with large vessel occlusion (AIS-LVO) refers to ischemic stroke caused by large vessel occlusion of internal carotid artery, middle cerebral artery and vertebrobasilar artery, which has the characteristics of large infarct, relatively poor outcome, higher disability and mortality. Therefore, early vascular recanalization and rescue of ischemic penumbra are the key to improve the outcome of patients with AIS-LVO. Mechanical thrombectomy (MT) has a definite effect on AIS-LVO. The current guidelines recommend that MT should be performed on the basis of IVT for AIS-LVO patients without contraindications of intravenous thrombolysis (IVT), the so-called bridging therapy. IVT can increase the risk of bleeding to a certain extent, delay MT and increase the cost of hospitalization. However, there are still many controversies about whether the patients with AIS-LVO can directly perform MT. This article reviews the comparative study of direct MT and bridging therapy in patients with anterior circulation AIS-LVO, hoping to provide reference for clinicians in the treatment of AIS-LVO.