ObjectiveTo investigate the characteristics of mitochondrial translational initiation factor 2 （MTIF2） gene methylation and its association with the development and progression of hepatocellular carcinoma （HCC）. MethodsMethSurv and EWAS Data Hub were used to perform the standardized analysis and the cluster analysis of MTIF2 methylation samples， including survival curve analysis， methylation signature analysis， the association of tumor signaling pathways， and a comparative analysis based on pan-cancer database. The independent-samples t test was used for comparison between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Cox proportional hazards model was used to perform the univariate and multivariate survival analyses of methylation level at the CpG site. The Kaplan-Meier method was used to investigate the survival differences between the patients with low methylation level and those with high methylation level， and the Log-likelihood ratio method was used for survival difference analysis. ResultsGlobal clustering of MTIF2 methylation showed that there was no significant difference in MTIF2 gene methylation level between different races， ethnicities， BMI levels， and ages. The Kaplan-Meier survival curve analysis showed that the patients with N-Shore hypermethylation of the MTIF2 gene had a significantly better prognosis than those with hypomethylation （hazard ratio ［HR］=0.492， P<0.001）， while there was no significant difference in survival rate between the patients with different CpG island and S-Shore methylation levels （P>0.05）. The methylation profile of the MTIF2 gene based on different ages， sexes， BMI levels， races， ethnicities， and clinical stages showed that the N-Shore and CpG island methylation levels of the MTIF2 gene decreased with the increase in age， and the Caucasian population had significantly lower N-Shore methylation levels of the MTIF2 gene than the Asian population （P<0.05）； the patients with clinical stage Ⅳ had significantly lower N-Shore and CpG island methylation levels of the MTIF2 gene than those with stage Ⅰ/Ⅱ （P<0.05）. Clinical validation showed that the patients with stage Ⅲ/Ⅳ HCC had a significantly lower methylation level of the MTIF2 gene than those with stage Ⅰ/Ⅱ HCC and the normal population （P<0.05）. ConclusionN-Shore hypomethylation of the MTIF2 gene is a risk factor for the development and progression of HCC.

ObjectiveTo investigate the therapeutic effect of Siegesbeckiae Herba water decoction （SWD） at different doses on atherosclerosis （AS） in a mouse model induced by a high-fat diet and analyze its potential mechanism of action. MethodsThirty-six male ApoE^-/- mice were randomly divided into six groups： blank control group， model group， low-dose， medium-dose， and high-dose SWD groups， and positive control group. Firstly， the AS mouse model was created by feeding mice a high-fat diet. After successful modeling， the low-， medium-， and high-dose SWD groups were intragastrically administered with SWD at 0.65， 1.3， 2.6 g·kg^-1， respectively. The positive control group was intragastrically administered with 30 mg·kg^-1 of atorvastatin calcium aqueous solution， while the blank and model groups received an equal volume of 0.9% sodium chloride solution via oral gavage， all administered for 12 weeks. During the administration period， the general condition of the mice was observed and recorded daily. Before sampling， color Doppler ultrasound was performed to observe the pathological changes in atherosclerotic plaques in the aortic wall of mice. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in aortic tissue in mice， and oil red O staining was used to detect the atherosclerotic plaque area in the aorta. Enzyme-linked immunosorbent assay （ELISA） was used to detect the serum lipid indices and the levels of interleukins （IL-1β， IL-4， IL-6， and IL-10） and tumor necrosis factor-α （TNF-α） in mice. Protein expression levels of IKKα， IKKβ， and NF-κB p65 in mouse aortic tissue were detected by Western blot. ResultsCompared with the blank control group， the model group showed a significant increase in body weight. The results of color Doppler ultrasound showed enhanced vascular wall echo， suggesting the presence of atherosclerotic plaques. HE staining showed foam cell aggregation， fibrous connective tissue proliferation， and vascular intima injury in the aortic tissue. Oil red O staining showed a significant increase in the plaque area in the aortic tissue （P<0.01）. ELISA results indicated significantly elevated levels of IL-1β， IL-6， TNF-α， total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein （LDL） in mouse serum （P<0.01）， as well as significantly decreased levels of IL-4， IL-10， and high-density lipoprotein （HDL） （P<0.01）. Western blot results showed that the expression of IKKα， IKKβ， and NF-κB p65 in mouse aortic tissue increased significantly （P<0.01）. Compared with those in the model group， mice in the middle- and high-dose SWD groups showed significant weight loss. In the high-dose group， the aortic vascular wall echoes were weakened， and the atherosclerotic plaques were reduced. The aortic lesions of mice in the medium- and high-dose SWD groups were significantly alleviated. The plaque area percentage showed an inverse correlation with the administered dose in all groups treated with SWD （P<0.05）. In the medium-dose SWD group， serum levels of IL-1β， IL-6， TNF-α， TC， TG， and LDL were significantly decreased （P<0.05， P<0.01）， while those of IL-4 and IL-10 were significantly increased （P<0.01）. In the high-dose SWD group， levels of IL-1β， IL-6， TNF-α， TC， TG， and LDL were significantly decreased （P<0.01）， while IL-4， IL-10， and HDL were significantly increased （P<0.01）. The IKKα and IKKβ expression was significantly decreased in the low-dose SWD group （P<0.05）， and IKKα， IKKβ， and NF-κB p65 were significantly decreased in the medium- and high-dose SWD groups （P<0.05， P<0.01）. ConclusionSWD may exert therapeutic effects on AS by regulating the expression of related inflammatory factors through the NF-κB signaling pathway， thereby reducing inflammation， plaque area， and lipid content in the body.

The pathogenesis of neurodegenerative diseases (NDDs) is fundamentally linked to complex and profound alterations in metabolic networks within the brain, which exhibit marked spatial heterogeneity. While conventional bulk metabolomics is powerful for detecting global metabolic shifts, it inherently lacks spatial resolution. This methodological limitation hampers the ability to interrogate critical metabolic dysregulation within discrete anatomical brain regions and specific cellular microenvironments, thereby constraining a deeper understanding of the core pathological mechanisms that initiate and drive NDDs. To address this critical gap, spatial metabolomics, with mass spectrometry imaging (MSI) at its core, has emerged as a transformative approach. It uniquely overcomes the limitations of bulk methods by enabling high-resolution, simultaneous detection and precise localization of hundreds to thousands of endogenous molecules—including primary metabolites, complex lipids, neurotransmitters, neuropeptides, and essential metal ions—directly in situ from tissue sections. This powerful capability offers an unprecedented spatial perspective for investigating the intricate and heterogeneous chemical landscape of NDD pathology, opening new avenues for discovery. Accordingly, this review provides a comprehensive overview of the field, beginning with a discussion of the technical features, optimal application scenarios, and current limitations of major MSI platforms. These include the widely adopted matrix-assisted laser desorption/ionization (MALDI)-MSI, the ultra-high-resolution technique of secondary ion mass spectrometry (SIMS)-MSI, and the ambient ionization method of desorption electrospray ionization (DESI)-MSI, along with other emerging technologies. We then highlight the pivotal applications of spatial metabolomics in NDD research, particularly its role in elucidating the profound chemical heterogeneity within distinct pathological microenvironments. These applications include mapping unique molecular signatures around amyloid β‑protein (Aβ) plaques, uncovering the metabolic consequences of neurofibrillary tangles composed of hyperphosphorylated tau protein, and characterizing the lipid and metabolite composition of Lewy bodies. Moreover, we examine how spatial metabolomics contributes to constructing detailed metabolic vulnerability maps across the brain, shedding light on the biochemical factors that render certain neuronal populations and anatomical regions selectively susceptible to degeneration while others remain resilient. Looking beyond current applications, we explore the immense potential of integrating spatial metabolomics with other advanced research methodologies. This includes its combination with three-dimensional brain organoid models to recapitulate disease-relevant metabolic processes, its linkage with multi-organ axis studies to investigate how systemic metabolic health influences neurodegeneration, and its convergence with single-cell and subcellular analyses to achieve unprecedented molecular resolution. In conclusion, this review not only summarizes the current state and critical role of spatial metabolomics in NDD research but also offers a forward-looking perspective on its transformative potential. We envision its continued impact in advancing our fundamental understanding of NDDs and accelerating translation into clinical practice—from the discovery of novel biomarkers for early diagnosis to the development of high-throughput drug screening platforms and the realization of precision medicine for individuals affected by these devastating disorders.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of toripalimab （Tor） combined with chemotherapy （CT） in the treatment of locally advanced or metastatic non-small cell lung cancer （NSCLC）. METHODS PubMed， the Cochrane Library， Embase， Web of Science， CBM， CNKI， Wanfang Data， and Health Technology Assessment （HTA） related websites were searched to collect the HTA reports， systematic reviews/meta-analyses and pharmacoeconomic studies of Tor+CT in the treatment of locally advanced or metastatic NSCLC from database/website inception to March 31， 2025. After data extraction and quality evaluation， the results of the included studies were analyzed descriptively. RESULTS A total of eleven studies were included， involving five systematic reviews/meta-analyses， and six pharmacoeconomic studies. Among the five systematic reviews/ meta-analyses， two were of high quality， while there was one each of moderate， low， and very low quality. All six pharmacoeconomic studies were of good quality. In terms of efficacy， compared with CT， Tor+CT significantly improved patients’ progression-free survival （PFS） and overall survival （P＜0.05）. In addition， compared with ipilimumab+CT， durvalumab， durvalumab+tremelimumab and sugemalimab+CT， Tor+CT could also improve the PFS （P＜0.05）. In terms of safety， there was no significant difference in the incidence of grade≥3 adverse events between patients receiving Tor+CT and CT （P＞0.05）； while Tor+CT had a lower incidence of grade≥3 adverse E-mail： events， compared with camrelizumab+CT， pembrolizumab+ 3233255290@qq.com ipilimumab， nivolumab+CT and atezolizumab+CT （P＜0.05）.In terms of cost-effectiveness， Tor+CT treatment had certain cost-effectiveness advantages， compared with CT. CONCLUSIONS Compared with CT， other programmed death-1/programmed death-ligand 1 inhibitors alone， or their combination with CT， Tor+CT for the treatment of locally advanced or metastatic NSCLC has good efficacy， safety and cost-effectiveness.

Objective To evaluate the bioequivalence of a single oral dose of ritonavir in fasted and fed conditions in healthy Chinese adult subjects with the test and reference formulations.Methods A single-center,open-label,randomized,single-dose,two-periods,two-sequence crossover design was used,and 64 subjects were enrolled in both the fasted and fed groups.The subjects received 100 mg of the test preparation or reference preparation orally per cycle,and the drug concentration of ritonavir in plasma was detected using the high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method.Pharmacokinetic parameters were estimated by a non-compartment model,and SAS 9.4 software was used for statistical analysis.Results Arithmetic mean values of the main pharmacokinetic parameters of the subject formulation of ritonavir tablets and the reference formulation in the fasting group:Cmax were(791.90±400.20)and(809.60±449.14)ng·mL-1;AUC0_t were(6 072.61±2 631.98)and(6 296.30±3 388.95)ng·h·mL-1;AUC0-∞ were(6 129.59±2 655.57)and(6 347.26±3 434.12)ng·h·mL-1,respectively.Arithmetic mean values of the main pharmacokinetic parameters of the subject formulation of ritonavir tablets and the reference formulation in the fed group:Cmax were(512.37±233.60)and(521.74±223.87)ng·mL-1;AUC0_t were(4 203.43±2 221.33)and(4 200.13±1 993.50)ng·h·mL-1;AUC0_∞ were(4 259.21±2 266.88)and(4 259.63±2 044.12)ng·h·mL-1.The 90％confidence intervals for the geometric mean ratios of Cmax,AUC0_t and AUC0_∞ of the prototype drug ritonavir in plasma after oral administration of 100 mg of the test and reference formulations of ritonavir tablets under fasting and fed conditions fell within the 80.00％to 125.00％equivalence interval.Conclusion The test and reference formulations of ritonavir tablets were bioequivalent under fasting and postprandial conditions.

Objective To analyze the current oral health status of middle-aged and elderly people in Wuhan,and to provide clinical evidence for preventing and promoting oral health among middle-aged and elderly people.Methods The data was col-lected from the annual health examination data system of Wuhan,which included 1994 patients aged 45～95.According to the World Health Organization(WHO)"Basic Methods of Oral Health Survey"(5 th edition),the data of caries,periodontal disease,dentition defect,dentition loss and denture restoration was mainly studied.Statistical methods such as Chi-square test and vari-ance analysis were used for data analysis.Results Among the 1994 subjects,1613 people(80.89％)were male and 218 people(10.93％)were older than 75 years old.The average numbers of caries and teeth loss were 2.68 and 2.03,respectively.The mean number of caries and tooth loss increased with age.The mean numbers of caries and tooth loss in 45～,55～,65～,75～,and 85～95 years old groups were 0.98 and 0.54,1.82 and 1.39,3.21 and 2.48,7.65 and 6.04,12.65 and 9.91,respective-ly.The difference among different age groups was statistically significant(P＜0.01).The proportion of restoration of teeth loss was also elevated with the increase of age(P＜0.01),and the difference of community periodontal index(CPI)among different age groups was also statistically significant(P＜0.01).The proportion of people in CPI1 group(shallow periodontal pocket)was decreased with the increase of age,while the proportion of people in CPI2 group(deep periodontal pocket)was increased with the increase of age(P＜0.01).Conclusion The overall oral health examination results of middle-aged and elderly people in Wuhan shows that the oral health status is slightly better when compared with the result of urban area in the 4th National Oral Health Examination.But caries,periodontal disease,tooth loss and unrepaired dentures are still serious in the elderly population.It is necessary to improve the prevention awareness of oral diseases in the elderly through regular oral examination,timely detection and treatment.At the same time,attention should be paid to dental restoration in the elderly population to improve the quality of life.

AIM: To observe the early retinal degeneration and activation of microglia in C57BL/6N(Crb1rd8/rd8)mice.METHODS:Totally 15 male SPF C57BL/6N mice and 15 male SPF C57BL/6J mice were raised normally, and fundus photography examinations were performed by Micron-Ⅲ at the time of 0, 4, 8, 12 wk of enrollment to calculate the number and area of retinopathy. At the end of experiment, all mice were sacrificed and the right eyeballs were removed to prepare retinal tissue slices. After HE staining, the retinal tissue morphology was observed under optical microscope while the location and level of CX3CR1 expression were detected in immunohistochemical staining. The left eyeballs were removed to isolate retina, then Western-Blot was used to analyze the expression of CD86 and CD206 proteins in retina, and the concentration of IL-1β, IL-6, TNF-α, IL-4 and IL-10 in retina was detected by electrochemiluminescence.RESULTS:The result of fundus photography examinations showed that the number of retinopathy in the C57BL/6N significantly increased at 4, 8, and 12 wk, and there were differences in variations compared with the C57BL/6J at the same time point(all P<0.05). In the changes in area of retinopathy, there was a difference between two groups at 12 wk(P<0.05), but no difference in variations within groups(both P>0.05). HE staining of retinal tissue showed that the retinal structure of C57BL/6N mice was abnormal, with loose and disordered cell arrangement, and the photoreceptor layer was obviously protruding to the inner side of retina with a drusen-like protrusion. The retinal structure of C57BL/6J mice was clearer, with orderly cell arrangement and no obvious abnormality. Immunohistochemical results showed that CX3CR1 was highly expressed in ganglion cell layer, inner and outer plexiform layer, photoreceptor cell layer and lesion in the retina of C57BL/6N mice, with a mean density of 0.285±0.056 in C57BL/6N and 0.189±0.084 in C57BL/6J mice(P<0.05). The results of Western-Blot showed that the expression of CD86 and CD206 in retina of C57BL/6N increased compared with that in C57BL/6J to varying degrees, and the difference of CD86 was statistically significant(P<0.05). The results of cytokine detection showed that the level of IL-1β, TNF-α in C57BL/6N was significantly higher than that of C57BL/6J, while IL-10 was significantly lower(all P<0.05).CONCLUSION: The retinal degeneration of C57BL/6N(Crb1rd8/rd8)mice progressed slowly and gradually aggravated with age. The retinal structure of the lesion was disordered and accompanied by microglial infiltration dominated by M1 polarization.

Smoking is the leading preventable risk factor for disease and death worldwide. Tobacco and its smoke contain a complex mix of over 9 500 chemical substances, including oxidative gases, heavy metals, and 83 known carcinogens. Long-term smoking is a significant risk factor for respiratory diseases such as acute lung injury, emphysema, and pulmonary fibrosis. Damage to alveolar epithelial cells (AECs) is a common pathological feature in these smoking-related lung diseases. AECs, which line the surface of the alveoli, play a crucial role in preventing overexpansion or collapse, secreting cell factors and surfactants, containing abundant mitochondria, and being essential for lung tissue maturation, gas exchange, metabolism, and repair after damage. Damage to these cells can lead to pulmonary edema and alveolar collapse. Cigarette smoke (CS) can disrupt alveolar epithelial cell function through various pathways, resulting in cell death, tissue damage, and the development of lung diseases.This review summarizes recent research on the damage caused by CS to AECs, showing that CS can promote cell death and damage through induction of oxidative stress, autophagy, endoplasmic reticulum stress, mitochondrial dysfunction, inflammation, and epithelial-mesenchymal transition. It also affects the proliferative function of alveolar type II epithelial cells. The review highlights that CS-induced oxidative stress is a key factor in causing various types of damage, with TRP ion channels serving as important triggers. Inhibiting CS-induced oxidative damage can significantly prevent cell death and subsequent diseases such as pulmonary emphysema. The activation of the same pathway induced by CS can lead to different types of cell damage, potentially encouraging the development of different diseases. CS can either directly induce or indirectly promote cell inflammation through endoplasmic reticulum stress, mitochondrial dysfunction, and senescence. There are interconnected relationships between these mechanisms, and SIRT1 is an important protein in preventing CS-induced AECs damage. Increasing SIRT1 activity can alleviate CS-induced autophagy, endoplasmic reticulum stress, and senescence in various cell damages; its substrate NAD⁺ is already used clinically, and its effectiveness in COPD treatment deserves further exploration. The impact of CS on cells varies based on concentration: lower concentrations stimulate stress responses or apoptosis, while higher concentrations lead to apoptosis or necrosis through various mechanisms, ultimately impairing lung epithelial function. When external stimuli exceed the cells’ self-healing capacity, they can cause damage to cells, lung epithelial barriers, and alveoli, promoting the development of related lung diseases. Key proteins that play a protective role may serve as potential targets to mitigate cell damage.This review provides insights into the various mechanisms through which CS induces damage to AECs, covering important transcription factors, DNA repair proteins, and membrane channel proteins, paving the way for the study of new mechanisms and pathways. However, there are still unanswered questions, such as the need for further exploration of the upstream pathways of CS-induced autophagy in AECs and the intrinsic mechanisms of CS in enhancing the stem cell properties of AECs and its relationship to the occurrence of lung cancer.It is expected that this article will provide a theoretical basis for future research on the mechanisms of lung epithelial cell damage caused by CS or its individual components and inspire clinical strategies for the prevention and treatment of smoking-related lung diseases.

As the global population continues to age, the incidence of Alzheimer’s disease (AD), one of the most common neurodegenerative diseases, continues to rise significantly. As the disease progresses, the patient’s daily living abilities gradually decline, potentially leading to a complete loss of self-care abilities. According to estimates by the Alzheimer’s Association and the World Health Organization, AD accounts for 60%-70% of all other dementia cases, affecting over 55 million people worldwide. The case number is estimated to double by 2050. Despite extensive research, the precise etiology and pathogenesis of AD remain elusive. Researchers have a profound understanding of the disease’s pathological hallmarks, which include amyloid plaques and neurofibrillary tangles resulting from the abnormal phosphorylation of Tau protein. However, the exact causes and mechanisms of the disease are still not fully understood, leaving a vital gap in our knowledge and understanding of this debilitating disease. A crucial player that has recently emerged in the field of AD research is the α7 nicotinic acetylcholine receptor (α7nAChR). α7nAChR is composed of five identical α7 subunits that form a homopentamer. This receptor is a significant subtype of acetylcholine receptor in the central nervous system and is widely distributed in various regions of the brain. It is particularly prevalent in the hippocampus and cortical areas, which are regions associated with learning and memory. α7nAChR plays a pivotal role in several neurological processes, including neurotransmitter release, neuronal plasticity, cell signal transduction, and inflammatory response, suggesting its potential involvement in numerous neurodegenerative diseases, including AD. In recent years, the role of α7nAChR in AD has been the focus of extensive research. Emerging evidence suggests that α7nAChR is involved in several critical steps in the disease progression of AD. These include involvement in the metabolism of amyloid β-protein (Aβ), the phosphorylation of Tau protein, neuroinflammatory response, and oxidative stress. Each of these processes contributes to the development and progression of AD, and the involvement of α7nAChR in these processes suggests that it may play a crucial role in the disease’s pathogenesis. The potential significance of α7nAChR in AD is further reinforced by the observation that alterations in its function or expression can have significant effects on cognitive abilities. These findings suggest that α7nAChR could be a promising target for therapeutic intervention in AD. At present, the results of drug clinical studies targeting α7nAChR show that these compounds have improvement and therapeutic effects in AD patients, but they have not reached the degree of being widely used in clinical practice, and their drug development still faces many challenges. Therefore, more research is needed to fully understand its role and to develop effective treatments based on this understanding. This review aims to summarize the current understanding of the association between α7nAChR and AD pathogenesis. We provide an overview of the latest research developments and insights, and highlight potential avenues for future research. As we deepen our understanding of the role of α7nAChR in AD, it is hoped that this will pave the way for the development of novel therapeutic strategies for this devastating disease. By targeting α7nAChR, we may be able to develop more effective treatments for AD, ultimately improving the quality of life for patients and their families.

Objective To investigate the effect of transcutaneous electrical acupoint stimulation(TEAS)on postoperative sore throat(POST)in patients undergoing double-lumen bronchial intubation based on general anesthesia.Methods A total of 103 patients,45 males and 58 females,aged 18-64 years,BMI 18-28 kg/m2,ASA physical status Ⅰ-Ⅲ,who received selective operation of double-lumen bronchial intubation under general anesthesia were selected.The patients were divided into two groups using the random number table method:TEAS group(n = 51)and control group(n = 52).In the TEAS group,TEAS on Tiantu acupoint and bilateral Hegu acupoints started 30 minutes before anesthesia induction,and the stimulation lasted until the patients were sent to the recovery room.In the control group,electrodes were placed on the same acupoints without electrical stimulation.The Mallampati grade,number of tracheal intu-bation attempts,compression of cricoid cartilage,resistance during intubation,and double-lumen endobron-chial tube(DLT)retention time were recorded.The incidence and severity of POST,VAS pain scores of sore throat,and the incidence of hoarseness 1 hour,6,and 24 hours after extubation were recorded.Results Compared with the control group,the incidence of POST,the incidence of POST level 1,and VAS pain scores of sore throat were significantly decreased 1 hour,6,and 24 hours after extubation(P＜0.05),the incidence of POST level 2 was significantly decreased 6 hours after extubation in the TEAS group(P＜0.05).There were no significant differences in the situations related to tracheal intubation,and the inci-dence of hoarseness 1 hour,6,and 24 hours after extubation between the two groups.Conclusion The transcutaneous electrical acupoint stimulation on Tiantu acupoint and bilateral Hegu acupoints can signifi-cantly reduce the incidence and severity of postoperative sore throat,and VAS pain scores of sore throat in patients undergoing double-lumen bronchial intubation.