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.

Acori Tatarinowii Rhizoma is the dried rhizome of Acorus tatarinowii in the family of Tennantiaceae, which has the efficacy of opening up the orifices and expelling phlegm, awakening the mind and wisdom, and resolving dampness and opening up the stomach. Modern studies have shown that volatile oil is the main active ingredient of Acori Tatarinowii Rhizoma, and α-asarone and β-asarone have been proved to be the active ingredients in the volatile oil of Acori Tatarinowii Rhizoma, with pharmacological effects such as anti-Alzheimer's disease, antiepileptic, anti-Parkinson's disease, antidepressant, anticerebral ischemia/reperfusion injury, anti-thrombosis, lipid-lowering, and antitumor. By summarising and outlining the pharmacological effects of α-asarone and β-asarone and elucidating the possible mechanisms of their pharmacological effects, we can provide theoretical basis for the further research and clinical application of Acori Tatarinowii Rhizoma.
Allylbenzene Derivatives ; Acorus/chemistry* ; Anisoles/chemistry* ; Rhizome/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Humans ; Animals

Acute lung injury(ALI) is a critical clinical condition primarily characterized by refractory hypoxemia and infiltration of inflammatory cells in lung tissue, which can progress into a more severe form known as acute respiratory distress syndrome(ARDS). Immune cells and inflammatory cytokines play important roles in the progression of the disease. Due to its unclear pathogenesis and the lack of effective clinical treatments, ALI is associated with a high mortality rate and severely affects patients' quality of life, making the search for effective therapeutic agents particularly urgent. Ginseng Radix et Rhizoma, the dried root of the perennial herb Panax ginseng from the Araliaceae family, contains active ingredients such as saponins and polysaccharides, which possess various pharmacological effects including anti-tumor activity, immune regulation, and metabolic modulation. In recent years, studies have shown that ginsenosides exhibit notable effects in reducing inflammation, ameliorating epithelial and endothelial cell injury, and providing anticoagulant action, indicating their comprehensive role in alleviating lung injury. This review summarizes the pathogenesis of ALI and the molecular mechanisms through which ginsenosides act at different stages of ALI development. The aim is to provide a scientific reference for the development of ginsenoside-based drugs targeting ALI, as well as a theoretical basis for the clinical application of Ginseng Radix et Rhizoma in the treatment of ALI.
Ginsenosides/pharmacology* ; Humans ; Acute Lung Injury/immunology* ; Animals ; Panax/chemistry* ; Drugs, Chinese Herbal

Food addiction refers to the individual dependence on certain specific foods (high-calorie foods) to the extent that it becomes difficult to control and manifests a series of addictive-like behavioral changes. Food addiction is an important factor in the development of human obesity and is also a core factor that most people cannot maintain weight loss or adhere to restrictive diets to maintain a healthy weight. A deeper understanding of food addiction and its neurobiological mechanisms will provide accurate targets for intervening in food addiction to improve obesity. Food addiction is characterized by compulsive, chronic and repetitive nature. The Yale Food Addiction Scale (YFAS), a scale specifically designed to assess food addiction, was developed in 2009 by modeling all the DSM-IV for substance dependence to be applicable to eating behavior. In 2016, Gearhardt developed the Yale Food Addiction Scale 2.0, which contains 35 survey questions, to align the YFAS scale with the diagnostic criteria for addictive disorders in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. One of the most valid and used animal models for food addiction is the mouse food self-administration model. The mouse food self-administration model was modified according to the rat cocaine addiction model, and the food addiction status of the animals was evaluated based on three behaviors: persistence of feeding response, feeding motivation, and compulsive feeding. Studies have shown that the neural circuits of the lateral hypothalamus-ventral tegmental area-nucleus accumbens and ventral tegmental area-prelimbic-nucleus accumbens are key neurobiological mechanisms that regulate food addiction. Dopaminergic neurons in the ventral tegmental area project to the nucleus accumbens (NAc) to facilitate food reinforcement, food reward, and food addiction. The corticotropin-releasing factor (CRF) secreted by the hypothalamus may mediate chronic stress-induced VTA-nucleus accumbens reward system dysfunction and promote food addiction in mice. Meanwhile, the nucleus accumbens receives glutamatergic projections from the prelimbic cortex, an integral part of the reward system. Specific inhibition of the PL-NAc neural circuit develops a food addiction-susceptible phenotype in mice. Furthermore, dopaminergic projections from the ventral tegmental area to the prelimbic cortex specifically inhibited the PL-NAc neural circuit to promote a food-addicted phenotype in mice. Additionally, neurotensin-positive neurons in the lateral septum (LS^Nts) project to the tuberal nucleus (TU) via GABA signaling to suppress hedonic feeding.

Objective To explore the clinical efficacies of different surgical methods for elderly patients with lumbar tuberculosis.Methods The clinical data of 289 elderly patients with lumbar tuberculosis admitted to Hebei Chest Hospital from August 2018 to August 2021 were retrospectively analyzed.According to surgical methods,the patients were divided into the posterior group(109 cases),the anterior and posterior combination group(81 cases),and the anterior group(99 cases).The time of bone graft and fusion,operation time,hospital stay,intraoperative blood loss,and complications of the three groups were collected and compared among the three groups.The spine Cobb angle was regularly determined,the correction degree was calculated;the levels of erythrocyte sedimentation rate(ESR),white blood cell count(WBC),and C-reactive protein(CRP)were collected and compared among the three groups;and the Frankel grading and visual analogue scale(VAS)scores of the three groups were compared.Results After a 2-year follow-up,there was no significant difference in the time of bone graft and fusion among the three groups(P>0.05),the anterior group had the shortest operation time,the posterior group had the shortest hospital stay,and the lowest intraoperative blood loss and incidence of complications,with statistically significant differences(P<0.05).The correction degree of the anterior and posterior combination group was better than that of the posterior group and the anterior group(P<0.05),and the Cobb angles after operation and at the last follow-up in the posterior group was better(P<0.05).The anterior and posterior combination group had better improvement effect on CRP and ESR at the last follow-up(P<0.05),the WBC level of the posterior group was lower(P<0.05).The proportions of patients in grade E of Frankel grading at the last follow-up in the three groups were higher than those after surgery(P<0.05);compared with the preoperative period,the VAS scores at the last follow-up of the three groups decreased(P<0.05),and the VAS score of the posterior group was lower(P<0.05).Conclusion The effects of anterior surgery,posterior surgery and anterior and posterior combined surgery in the treatment of elderly lumbar tuberculosis are good,and the approach method can be scientifically and reasonably formulated according to patients' physical condition to improve the clinical treatment effect.

Objective:To study the serological characteristics of ABO*A2.08 subtype and explore its genetic molecular mechanism.Methods:ABO blood group identification was performed on proband and her family members by routine serological methods.ABO genotyping and sequence analysis were performed by polymerase chain reaction-sequence specific primer(PCR-SSP),and direct sequencing of PCR products from exons 6 and 7 of ABO gene were directly sequenced and analyzed.The effect of gene mutation in A2.08 subtype on structural stability of GTA protein was investigated by homologous protein conserved analysis,3D molecular modeling and protein stability prediction.Results:The proband's serological test results showed subtype Ax,and ABO genotyping confirmed that the proband's genotype was ABO*A207/08.Gene sequencing of the proband's father confirmed the characteristic variation of c.539G＞C in the 7th exon of ABO gene,leading to the replacement of polypeptide chain p.Arg180Pro(R180P).3D protein molecular modeling and analysis suggested that the number of hydrogen bonds of local amino acids in the protein structure was changed after the mutation,and protein stability prediction showed that the mutation had a great influence on the protein structure stability.Conclusion:The mutation of the 7th exon c.539G＞C of ABO gene leads to the substitution of polypeptide chain amino acid,which affects the structural stability of GTA protein and leads to the change of enzyme activity,resulting in the A2.08 phenotype.The mutated gene can be stably inherited.

Chronic graft-versus-host disease(cGVHD)is one of a major complication that affecting the long-term survival and living quality of patients after allogeneic hematopoietic stem cell transplantation,with the incidence of 30％-70％.Unlike acute GVHD,cGVHD involves a large number of immune cells and cytokines in addition to T cell,which is activated abnormally by the donor,and cytokine storms,which characterized by infiltration of donor lymphocytes and damage to host target organ.Recent studies have further made progress in targeting related immune cells and cytokines.In this review,the pathogenesis and therapeutic prospects of cGVHD were summarized from the perspectives of classical innate and adaptive immunity.

Sjögren's syndrome(SS)is a chronic autoimmune disease that affects exocrine glands, especially salivary and lacrimal glands. The main clinical manifestations are dry mouth and dry eyes, but also multi-organ and multi-system can be involved. Cold agglutinin disease(CAD)is an autoimmune disease characterized by red blood cell agglutination in the blood vessels of extremities caused by cold agglutinin at low temperature, resulting in skin microcirculation disturbance, or hemolytic anemia. Cold agglutinin disease is divided into two categories, primary cold agglutinin disease and secondary cold agglutinin disease. Primary cold agglutinin disease is characterized with cold agglutinin titer of 1 ∶4 000 or more and positive Coomb's test. However, the Coomb's test is not necessarily positive and the cold agglutinin titer is between 1 ∶32 and 1 ∶4 000 in secondary cold agglutinin disease. Here, we reported an elderly patient admitted to hospital due to fever. He was diagnosed with respiratory infection, but he showed incompletely response to the anti-infection treatment. Further laboratory tests showed the patient with positive ANA and anti-SSA antibodies. Additionally, the patient complained that he had dry mouth and dry eyes for 1 year. Schirmer test and salivate gland imaging finally confirmed the diagnosis Sjogren's syndrome. During the hospital stay, the blood clots were found in the anticoagulant tubes. Hemolytic anemia was considered as the patient had anemia with elevated reticulocytes and indirect bilirubin. In addition, further examination showed positive cold agglutination test with a titer of 1 ∶1 024, and cold agglutinin disease was an important type of cold-resistant autoimmune hemolytic anemia. Furthermore, the patient developed cyanosis after ice incubating at the tip of the nose. Hence, the patient was diagnosed as CAD and he was successfully treated with glucocorticoids instead of anti-infection treatments. Hence, the patient was diagnosed with SS combined with secondary CAD. SS combined CAD are rarely reported, and they are both autoimmune diseases. The abnormal function of B lymphocytes and the production of autoantibodies might be the common pathogenesis of them. Cold agglutinin disease can lead to severe hemolytic anemia, even life-threatening. In clinical practice, timely recognizing and dealing with CAD might promote the prognosis of the patient.
Male ; Humans ; Aged ; Anemia, Hemolytic, Autoimmune/diagnosis* ; Sjogren's Syndrome/diagnosis* ; Anemia, Hemolytic/complications* ; Dry Eye Syndromes/complications* ; Autoantibodies

The alphaherpesvirus envelope glycoprotein I,encoded by the non-essential gene US7,plays an important role in the pathogenic mechanism of the virus.Recent studies have shown that envelope glycoprotein gI is important in the assembly of alpha herpesvirus particles and the diffusion of viral particles,by participating in secondary envelope coating and promoting in-tercellular transmission.The protein also has essential roles in promoting the axonal transport of the virus along neurons and the anti-host immune response,thereby affecting virulence.This article discusses the molecular mechanism through which gI affects the virulence of alpha herpes virus,thus providing a theoretical basis for in-depth study of the function of this protein.

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.