Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

Zishen Huoxue decoction (ZSHX) enhances cardiomyocyte viability following hypoxic stress; however, its upstream therapeutic targets remain unclear. Network pharmacology and RNA sequencing analyses revealed that ZSHX target genes were closely associated with mitophagy and apoptosis in the mitochondrial pathway. In vitro, ZSHX inhibited pathological mitochondrial fission following hypoxic stress, regulated FUN14 domain-containing protein 1 (FUNDC1)-related mitophagy, and increased the levels of mitophagy lysosomes and microtubule-associated protein 1 light chain 3 beta II (LC3II)/translocase of outer mitochondrial membrane 20 (TOM20) expression while inhibiting the over-activated mitochondrial unfolded protein response. Additionally, ZSHX regulated the stability of beta-tubulin through Sirtuin 5 (SIRT5) and could modulate FUNDC1-related synergistic mechanisms of mitophagy and unfolded protein response in the mitochondria (UPR^mt) via the SIRT5 and -β-tubulin axis. This targeting pathway may be crucial for cardiomyocytes to resist hypoxia. Collectively, these findings suggest that ZSHX can protect against cardiomyocyte injury via the SIRT5-β-tubulin axis, which may be associated with the synergistic protective mechanism of SIRT5-β-tubulin axis-related mitophagy and UPR^mt on cardiomyocytes.
Mitophagy/drug effects* ; Tubulin/genetics* ; Animals ; Myocytes, Cardiac/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Sirtuins/genetics* ; Unfolded Protein Response/drug effects* ; Myocardial Ischemia/genetics* ; Rats ; Humans ; Rats, Sprague-Dawley ; Apoptosis/drug effects* ; Male

Objective Establish the fingerprint of the group and optimize the extraction process of the Yunpi Huatan Tongqiao decoction.Methods The macroscopic characterization and similarity analysis of the extract fingerprint were carried out by applying the total statistical moment method.With baicalin,wogonin,rosmarinic acid,liquiritin,glycyrrhizic acid and paste yield as key quality attributes,and extraction time,water addition and extraction times as key process parameters,the optimal extraction process was selected by AHP-independent weight method,and the process was verified.Results Establishing a total statistical moment similarity evaluation method,and the average statistical moment similarity of the total amount of fingerprints of different extraction methods was 0.8807.The ANOVA results of the process evaluation model function are displayed that P<0.0001,R2=0.9904,indicating that the model was statistically significant.The best extraction process was determined as follows:adding 10-fold volume of water in the whole prescription,extracting for 1.5 h and extracting twice.Conclusion The total statistical moment analysis method that conforms to the fingerprint characteristics of the fingerprint of the extract was established,which was stable and reliable,which provided a reference basis for the quality control of the whole process of the subsequent process research.

Circulating tumor DNA (ctDNA) is cell-free DNA released by tumors or circulating tumor cells, containing abundant tumor-specific information that can serve as biomarkers for cancer early screening, monitoring, prognosis, and prediction of treatment response. This is particularly attractive in the field of gastric cancer, where high-quality screening, monitoring, and prediction methods are currently lacking. Gastric cancer exhibits significant tumor heterogeneity, with large differences in genetic and epigenetic characteristics among different subgroups. Methylated ctDNA has high sensitivity and specificity, which can help clarify tumor genotyping and facilitate the formulation of precise diagnostic and therapeutic strategies. Furthermore, numerous studies have confirmed the unique advantages of methylated DNA in predicting treatment response, adjuvant therapy, and drug resistance assessment, which may be used in the future to enhance the efficacy of chemotherapy regimens and improve patient chemotherapeutic response, and even treat multidrug resistance. However, there are several challenges associated with methylated ctDNA, such as low sensitivity and specificity at single-target sites, limited association between some gastric cancer subtypes and ctDNA, off-target risks, and the lack of large-scale and high-quality clinical research evidence. This review mainly summarizes current research on the methylation status of ctDNA in gastric cancer and connects these findings to early screening, recurrence monitoring, and potential treatment opportunities for gastric cancer. With advances in technology and the deepening of interdisciplinary research, ctDNA detection will reveal more disease information and become an essential foundation for gastric cancer research and precision medicine treatment.

Objective To observe the effect of extracorporeal shockwave therapy (ESWT) in regulating endothelial cell phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression on lower ex-tremity vascular lesion and its possible mechanism.Methods Twenty-four 2-month-old healthy male SD rats were randomly divided into the three groups:control group (group A),diabetes angiopathy group (group B),diabetes angiopathy+ESWT group (group C).The group B and C were fed with high fat and high sugar and intraperitoneally injected with streptozotocin 60 mg/kg to establish the rat model of diabetes vascular lesion. The group C received ESWT at 1 week (T1),2 weeks (T2),3 weeks (T3) and 4 weeks (T4) after modeling,and the blood stream velocity of rat femoral artery vascular lesion area and vascular internal diameter were measured at T4 by ultrasound.At the end of ESWT,the rats were immediately killed for taking their femoral arteries and gastrocnemius.The structures of the femoral arteries in each group were observed under electron microscopy.Western blot was used to detect the expression levels of PTEN,PI3K and Akt proteins,while qRT-PCR was used to detect the expression levels of PTEN mRNA.Immunofluorescence was used to detect the expression level of CD31 in gastrocnemius muscle .Results The peak systolic flow velocity and end-dias-tolic flow velocity of femoral artery at T4 in group B and C were significantly lower than those in group A (P<0.05),but group C was higher than group B (P<0.05).The internal diameter of femoral artery had no statistical difference among 3 groups (P>0.05).The PTEN expression level in group B and group C was sig-nificantly lower than that in group A (P<0.05),while group C was higher than group B (P<0.05).The ex-pression levels of PI3K and Akt in group B were higher than those in group A (P<0.05),and group C was lower than group B (P<0.05).The PTEN mRNA expression level in group B and group C was significantly lower than that in group A (P<0.05),but group C was higher than group B (P<0.05).Under electron mi-croscopy,it was observed that after ESWT,the endothelial cell damage in group C was obvious when com-pared with group B.The CD31 expression level in group B and group C was significantly lower than that in group A (P<0.05),but group C was higher than group B (P<0.05).Conclusion ESWT could improve the vascular function,increase the peak velocity during systolic period of femoral artery in diabetes rats and im-prove the microvessel density of gastrocnemius muscle by up-regulating PTEN in lower extremity artery and down-regulating PI3K and Akt in diabetes rats.

The utilization of optimal orthodontic force is crucial to prevent undesirable side effects and ensure efficient tooth movement during orthodontic treatment.However,the sensitivity of existing detection techniques is not sufficient,and the criteria for evaluating optimal force have not been yet established.Here,by employing 3D finite element analysis methodology,we found that the apical distal region(A-D region)of mesial roots is particularly sensitive to orthodontic force in rats.Tartrate-resistant acidic phosphatase(TRAP)-positive osteoclasts began accumulating in the A-D region under the force of 40 grams(g),leading to alveolar bone resorption and tooth movement.When the force reached 80 g,TRAP-positive osteoclasts started appearing on the root surface in the A-D region.Additionally,micro-computed tomography revealed a significant root resorption at 80 g.Notably,the A-D region was identified as a major contributor to whole root resorption.It was determined that 40 g is the minimum effective force for tooth movement with minimal side effects according to the analysis of tooth movement,inclination,and hyalinization.These findings suggest that the A-D region with its changes on the root surface is an important consideration and sensitive indicator when evaluating orthodontic forces for a rat model.Collectively,our investigations into this region would aid in offering valuable implications for preventing and minimizing root resorption during patients'orthodontic treatment.

Objective:Cardiac arrest (CA) represents a significant public health challenge, posing a substantial threat to individual health and survival. To enhance the survival rates of patients experiencing out-of-hospital cardiac arrest (OHCA), Baoan District in Shenzhen City has undertaken exploratory initiatives and practical interventions, yielding promising preliminary outcomes.Methods:1.Innovate emergency medical services by developing a "four-circle integration" system that connects to the hospital. This system encompasses the social emergency medical system, the out-of-hospital emergency medical system, the in-hospital emergency medical service system, and the intensive care treatment system. 2.Develop a comprehensive model for the construction of a social emergency medical training system, characterized by party leadership, government oversight, departmental coordination, professional guidance, technological support, and community involvement, termed the "Baonan Model." Additionally, establish evaluation criteria to assess the effectiveness of the social emergency medical training system in Baonan District; 3. Develop a cardiac arrest registration system and a social emergency medical training management system for Baonan District; 4. Enhance the proficiency in treatment techniques and the quality of cardiopulmonary resuscitation among emergency medical professionals; 5. Strengthen and advance the development of a "five-minute social rescue network" to address the critical "emergency window period." .Result:In Baonan District, 9.18% of the public is trained in emergency medical skills. The bystander CPR rate for OHCA is 26.11%, AED use is at 4.78%, the 30-day survival rate is 6.31%, and the discharge survival rate is 4.44%.Conclusion:The implementation of the aforementioned measures can substantially enhance the survival rate of patients experiencing OHCA at the time of discharge.

Lung cancer is the top cause of cancer deaths globally.Advances in immune checkpoint inhibitors(ICIs)have transformed cancer treatment,but their use in lung cancer has led to more side effects.This study examined if past pulmonary tuberculosis(TB)affects ICIs'effectiveness and safety in lung cancer treatment.We reviewed lung cancer patients treated with ICIs at Beijing Chest Hospital from January 2019 to August 2022.We compared outcomes and side effects between patients with and without prior TB.Of 116 patients(40 with TB history,76 without),prior TB didn't reduce treatment effectiveness but did increase severe side effects.Notably,older patients(≥65 years)faced a higher risk of severe side effects.Detailed cases of two patients with severe side effects underscored TB as a risk factor in lung cancer patients receiving ICIs,stressing the need for careful monitoring and personalized care.

Influenza is a contagious respiratory disease caused by influenza viruses, and the burden of severe disease is commonly seen in high risk populations. Influenza vaccination is an effective way to prevent influenza and its complications, especially for high risk populations. Although some countries have included influenza vaccine in their national immunization programs, influenza vaccination rates remain low globally in high risk populations. The influenza vaccine in China is still a non-immunization program vaccine that is voluntarily vaccinated at its own expense, and the influenza vaccine immunization strategy is different across the country. There is still a gap between the vaccination rate of the influenza vaccine and that of developed countries. It is an urgent problem to further optimize the whole population immunization strategy of influenza vaccine in China, strengthen the publicity of the whole population immunization strategy of influenza vaccine, and reduce the disease burden of influenza in China.