Serving as cerebral macrophages， microglial cells are meticulously regulated by the microenvironment of the central nervous system.In response to various environmental and cellular stresses， microglial cells are rapidly activated and exhibit either pro-inflammatory or anti-inflammatory phenotypes to maintain brain tissue homeostasis， and during this process， significant changes are observed in glucose metabolism of microglial cells. Aerobic glycolysis is the primary energy source for pro-inflammatory microglial cells， while oxidative phosphorylation is the energy source for anti-inflammatory microglial cells.This article systematically elaborates on glucose metabolism and glucose metabolic reprogramming pathways in microglial cells， as well as their role in central nervous system diseases. In addition， this article also discusses the potential of targeting glucose metabolic reprogramming in microglial cells for the treatment of related diseases.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

TCM proposes that the core pathological mechanism of depression is"deficient qi with stagnation and heat",with the following pathogenic characteristics and evolution patterns:"deficient qi"as the nature,and deficiency in nature is in spleen,and deficiency in superficiality is in brain;"stagnation"is the superficiality,and qi stagnation,phlegm stagnation,and blood stagnation are in the brain collaterals;"heat"fires the brain collaterals,depression raised the heat,and excessive heat accumulated to stagnation.Based on the understanding of the pathogenesis of depression caused by stress sensitization in modern medicine,this article explored the potential association between this mechanism and the core pathogenesis of"deficient qi with stagnation and heat".It proposed that tonifying deficiency,promoting circulation,and clearing heat are the basic treatment principles for depression.By inhibiting inflammatory reactions and improving the stress sensitization state of neurons and glial cells,TCM compound formulas can exert multi-target and multi-dimensional therapeutic characteristics.

Objectives: . Branchio-oto syndrome (BOS) primarily manifests as hearing loss, preauricular pits, and branchial defects. EYA1 is the most common pathogenic gene, and splicing mutations account for a substantial proportion of cases. However, few studies have addressed the structural changes in the protein caused by splicing mutations and potential pathogenic factors, and several studies have shown that middle-ear surgery has limited effectiveness in improving hearing in these patients. BOS has also been relatively infrequently reported in the Chinese population. This study explored the genetic etiology in the family of a proband with BOS and provided clinical treatment to improve the patient’s hearing. Methods: . We collected detailed clinical features and peripheral blood samples from the patients and unaffected individuals within the family. Pathogenic mutations were identified by whole-exome sequencing and cosegregation analysis and classified according to the American College of Medical Genetics and Genomics guidelines. Alternative splicing was verified through a minigene assay. The predicted three-dimensional protein structure and biochemical experiments were used to investigate the pathogenicity of the mutation. The proband underwent middle-ear surgery and was followed up at 1 month and 6 months postoperatively to monitor auditory improvement. Results: . A novel heterozygous EYA1 splicing variant (c.1050+4 A>C) was identified and classified as pathogenic (PVS1(RNA), PM2, PP1). Skipping of exon 11 of the EYA1 pre-mRNA was confirmed using a minigene assay. This mutation may impair EYA1-SIX1 interactions, as shown by an immunoprecipitation assay. The EYA1-Mut protein exhibited cellular mislocalization and decreased protein expression in cytological experiments. Middle-ear surgery significantly improved hearing loss caused by bone-conduction abnormalities in the proband. Conclusion . We reported a novel splicing variant of EYA1 in a Chinese family with BOS and revealed the potential molecular pathogenic mechanism. The significant hearing improvement observed in the proband after middle-ear surgery provides a reference for auditory rehabilitation in similar patients.

Objective To explore any effect of calorie restriction on the proliferation of satellite cells in the skeletal muscles of elderly rats.Methods Twelve male C57BL rats aged 12 or 13 months were randomly divided in to an experimental group and a control group,each of 6.The control group was fed 75.09 kJ/d as normal,while the experimental group was provided with 45.05 kJ/d (60％ of normal).The intervention lasted for 15 weeks and each rat's weight was measured every week.After the intervention,limb muscle satellite cells were sorted by fluorescenceactivated cell sorting after digestion,and the cell cycle was analyzed.Western blotting was used to assess the expression of cyclin A,D1 and E.Results There was no significant difference in the average weight of the two groups before the experiment.After the 15 weeks the average weight of the experimental group had decreased significantly (to 19.5±0.4 g),and it was significantly lighter than that of the control group (31.9±0.5 g).The average percentage of the satellite cells in the G0/G1 phase had decreased significantly in the experimental group,but the percentage in the S phase had increased significantly.The expression of cyclin A and E was significantly greater in the experimental group compared with the control group,but the expression of cyclin D1 had decreased significantly.Conclusion Caloric restriction can delay the proliferation of satellite cells in the skeletal muscles of elderly mice.

Objective To study the mechanism of oxidative stress involved in the pathogenesis and relapse of acute monocytic leukemia (M5 ).Methods We detected reactive oxide species (ROS)levels,conducted plasma analysis obtained from 76 M5 patients at diagnosis and at relapse,and observed the ultrastructure of mitochondria of mononuclear cells in peripheral blood by transmission electron microscope.Results Compared with that in the control group,the average fluorescence intensity of intracellular ROS was significantly increased in M5 groups, especially in the relapse patients (P < 0.05 ).Low total antioxidative capacity (T-AOC)and antioxidant enzyme activity were characteristic of M5 at both diagnosis and relapse. However, lactate dehydrogenase (LDH ), malondialdehyde (MDA)and 8-hydroxy-2’-deoxyguanine (8-OHdG)increased significantly at both diagnosis and relapse (P < 0.05 ).Prominent ultrastructural abnormalities (mitochondrial swelling,outer membrane blebs,and aberrant cristae disorder)were present in patients with primary M5,and they were obviously abnormal in relapsing M5 patients.Conclusion Oxidative stress is the initiating factor of M5.Mitochondria are the main intracellular location for ROS generation.To maintain the dynamic balance between ROS and antioxidant defence may be the critical factor for preventing relapse.

Objective To compare eradication rates,safety and compliance of minocycline quadruple and tailored therapies in patients retreated for Helicobacter pylori (H.pylori) infection.Methods Between January 2014 and June 2014,135 patients with dyspepsia (18-70 years) and H.pylori infection after at least one previous eradication treatment at a tertiary hospital were randomly assigned to a 10-day treatment with minocycline quadruple therapy versus tailored triple regimen of PPI,amoxicillin and a third antibiotic.In the group of tailored therapy,medications were adjusted based on clarithromycin sensitivity and cytochrome P450 isoenzyme 2C19 genotype.Eradication status was assessed 4-12 weeks after treatment.Results Although H.pylori eradication rates were higher in the minocycline therapy group than that in the tailored therapy group in intention-to-treat [84.1％ (95％ CI 75.0％-93.2％) vs 75.8％ (95％ CI 65.1％-86.5％),P =0.245] and per-protocol [88.3％ (95％ CI 80.3％-96.3％) vs 79.7％ (95％CI 69.7％-89.7％),P =0.197] analyses,the differences between the two groups were not statistically significant.The incidence of adverse effects and compliance between the two groups were also comparable.Conclusions The tailored therapy in this study had a poor eradication efficacy in the retreated patients with H.pylori infection.Minocycline quadruple therapy achieved a relatively satisfactory eradication efficacy and may be an alternative choice for the retreatment of H.pylori infection.Clinical trial registration Chinese Clinical Trial Registry,ChiCTR-TRC-13003975.

BACKGROUND:Bone marrow stem cells are defined by their multi-potential ability, and can be differentiated into intrinsic cells in the kidney.
OBJECTIVE:To study the effects of mobilizing autologous bone marrow stem cells by granulocyte colony-stimulating factor plus stem cellfactor on cellapoptosis and proliferation of rats with renal ischemia-reperfusion injury.
METHODS:Total y 160 male Sprague-Dawley rats were randomly divided into four groups:control group, model group, cytokine treatment group, cytokine control group. Rat models of unilateral renal ischemia-reperfusion injury were established in the model and cytokine treatment groups. Rats in the cytokine treatment group and cytokine control group received subcutaneous injection of granulocyte colony-stimulating factor (50μg/kg) and stem cellfactor (200μg/kg), once a day, for 5 continuous days. Rats in the model and control groups had no treatment. Apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method, and the expression of CD34-positive cells, Caspase-3, Bcl-2, proliferating cellnuclear antigen in the kidney were measured using immunohistochemistry staining.
RESULTS AND CONCLUSION:The number of CD34-positive cells in renal tissue of the cytokine treatment group was significantly higher than that of the control group and model group (P<0.05). The apoptotic index and expression of Capase-3 in the model group and cytokine treatment group were higher than those in the control group and cytokine control group (P<0.05). The apoptotic index and expression of Capase-3 in the cytokine treatment group were lower than that in the model group (P<0.05). The expression of Bcl-2 in the model group and cytokine treatment group was higher than that in the control group and cytokine control group (P<0.05). The expression of Bcl-2 in the cytokine treatment group was higher than that in the model group (P<0.05);however, as time went on, Bcl-2 expression was obviously decreased. Proliferating cellnuclear antigen expressed both in the model group and in the cytokine treatment group. Additional y, the proliferative index reached peak at 24 days in the model group, and then decreased gradual y;while in the cytokine treatment group, it reached the peak at 10 days, maintained a high level until the 17th day, and then decreased gradual y. Mobilization of autologous bone marrow stem cells by combination of granulocyte colony-stimulating factor and stem cellfactor can increase proliferation and decrease apoptosis of renal tubular epithelial cells after renal ischemia-reperfusion injury, and thus, promote the recovery from renal tubular injury.

Objective To estimate the therapeutic value of plasma exchange (PE) in severe bullous dermatoses and drug eruption. Methods Plasma exchange was carried out to treat 47 patients with severe dermatoses including 15 cases of pemphigus, 17 cases of bullous pemphigoid and 15 cases of drug eruption who were intolerant or unresponsive to glucocorticosteroids and or immunosuppressants. Cobe Spectra blood cell separator was utilized to collect plasma and cell components from patients' blood, and the replacement fluid and cell components were infused back into patients. Patients received 1 to 3 sessions of plasma exchange. Results Of the 47 patients, 44 (93.62%) achieved satisfactory efficacy with relief of clinical symptoms and improvement of laboratory parameters 2 to 3 days after the plasma exchange. Side effects occurred in 11 (23.4%) patients, which included fever, shivering, numbness of limbs, pruritus and convulsion. Conclusion Plasma exchange is beneficial for the control of severe drug eruption and bullous dermatoses.

BACKGROUND: There have been no reports available about the direct effect of beer on serum enzyme activity.OBJECTIVE: To observe the changes of the activity of various serum enzymes of the subjects in the in vivo and in vitro experiments after drinking bear.DESIGN: An observational controlled experiment.SETTING: The Institute of Basic Medicine of Taishan Medical College.PARTICIPANTS: The experiment was performed at the Institute of Basic Medicine of Taishan Medical College between March 2005 and April 2005.We selected 17 college students, aged 19 to 35 years, from Taishan Medical College, including undergraduate students and graduate students. In formed consents were obtained from the subjects before the experiment was conducted.METHODS: ① In vivo experiment: 3 mL of venous blood was collected from the subjects 3 hours after the ordinary diet as the control. Then, the subjects drank beer at an amount of 4 mL/kg according to their body mass immediately. 3 mL of blood was collected respectively 15, 30, 45, 60, 90,120, 80 minutes later to measure the changes of the activity of alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, al kaline phosphatase, creatine kinase , lactate dehydrogenase, diastase and lipase. ② In vitro experiment: 17 fresh serum samples were added into two test tubes separately with 0.5 mL of serum in each tube. 20 μL of normal saline was added to the tube of the control and 20 μL of beer was added into the test tube. The direct effect of beer on the activity of various enzymes was observed.MAIN OUTCOME MEASURES: The changes of the activity of alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, al kaline phosphatase, creatine kinase , lactate dehydrogenase, diastase and lipase of the serum on the in vivo and in vitro experiment .RESULTS: Totally 17 students were involved and all the students entered the stage of result analysis with no loss in the midway. ① In vivo experiment: Beer significantly decreased the activity of serum aspartate aminotransferase (418.08 ±58.68,383.41 ±63.01)nkat/L, significantly in creased the activity of serum alkaline phosphatase, (367 8.57±436.25,396 2.96±400.91)nkat/L (x2=19.00-20.00,P ＜ 0.01). The activity of other enzymes was all increased at different degrees. ② In vitro experiment: Beer inhibited the activity of various enzymes in vitro to a certain degree.CONCLUSION: Beer has some effect on enzyme activity in vivo and in vitro, thus affecting the body metabolism. Over drinking beer can affect health. In the routine detection of serum enzymes, attention should be given to avoid the interference caused by over drinking beer to make sure the experimental results are precise and reliable.