ObjectiveTo investigate the characteristics of gray matter structure and clinical symptoms in patients with Alzheimer's disease （AD） comorbid with apathy （AD-A）. MethodsThe study included 30 patients with AD-A， 30 AD disease patients without apathy （AD without apathy， AD-NA）， and 30 healthy controls （HCs） matched in gender， age， and years of education. All participants underwent a comprehensive neuropsychological assessment and magnetic resonance imaging （MRI） scans. Voxel-based morphometry （VBM） was used to analyze changes in gray matter volume among the three groups. Additionally， the correlation between the identified abnormal brain regions and apathy scale scores was analyzed. ResultsThere were no statistically significant differences among the three groups in terms of age， gender， years of education， or total intracranial volume. Compared with the HCs group， both the AD-A and AD-NA groups showed significantly lower scores in cognitive function （P<0.001）. The AD-A group exhibited significantly higher apathy scale scores compared with the AD-NA group （P<0.001）. Compared with the AD-NA group， the AD-A group showed reduced gray matter volume in the bilateral caudate nucleus， left orbitofrontal cortex， lingual gyrus， inferior frontal gyrus， superior frontal gyrus， entorhinal cortex， right middle frontal gyrus and posterior cingulate cortex （FWE-corrected， P<0.05 for all）. Compared with the HCs group， the AD-A group exhibited reduced gray matter volume in the bilateral middle temporal gyrus， left fusiform gyrus， calcarine sulcus， postcentral gyrus， right inferior frontal gyrus and supramarginal gyrus （FWE-corrected， P<0.05 for all）. Compared with the HCs group， the AD-NA group showed reduced gray matter volume in the left precuneus， inferior temporal gyrus， and right inferior temporal gyrus （FWE-corrected， P<0.05 for all）. In the AD-A group， changes in the gray matter volume of the left caudate nucleus （r= -0.557， P=0.002） and right middle frontal gyrus （r=-0.620， P=0.001） were negatively correlated with the apathy evaluation scale （AES） scores. ConclusionPatients in the AD-A group exhibited significant atrophy in the frontal-temporal-basal ganglia circuit， and the degree of gray matter atrophy was correlated with the severity of apathy.

Locally advanced non-small cell lung cancer (NSCLC) is a highly heterogeneous disease. For patients with driver gene-negative, unresectable NSCLC, traditional treatment primarily involves concurrent chemoradiotherapy. With the advent of the immunotherapy era, integrated treatment strategies combining concurrent chemoradiotherapy with immunotherapy have significantly improved therapeutic outcomes and substantially extended survival periods. This article summarizes the interaction mechanisms and clinical research progress of radiotherapy, chemotherapy, and immune checkpoint inhibitors in the treatment of NSCLC. This review also provides perspectives on the development of therapies in the future and predictive biomarkers, serving as a reference for treatment options for patients with unresectable locally advanced NSCLC.

Brain metastases are the most common intracranial tumors, and their incidence is increasing with the improvement of systemic treatments and survival rates. Optimal treatment usually requires a multidisciplinary approach, including radiotherapy, surgical resection, chemotherapy, targeted therapy, and immunotherapy. Stereotactic radiotherapy, compared to whole-brain radiotherapy, offers improved local control rates and reduced risk of neurocognitive impairment, and has become a new standard option for the treatment of brain metastases. Additionally, the widespread use of targeted and immune therapies in brain metastases has significantly improved the survival of some patients. This article reviews and integrates recent literature on the treatment of brain metastases and analyzes the role of stereotactic radiotherapy in comprehensive treatment, aiming to provide a reference for the selection of clinical treatment plans.

ObjectiveTo investigate whether the effects of paeonol （Pae） on angiotensin Ⅱ （AngⅡ）-induced senescence in vascular smooth muscle cells （VSMCs） were related to angiotensinogen of silencing regulatory information factor 6 （SIRT6）/adenosine diphosphate ribose polymerase 1 （PARP1） signaling pathway in VSMCs. MethodThe model of VSMC-stress aging induced by AngⅡ （100 nmol·L^-1） was established. The rats were divided into normal group， model group， low， medium， and high-concentration Pae groups （30， 60， 120 μmol·L^-1）. The positive rate of cell senescence was detected by SA-β-Gal staining， the ability of cell proliferation was detected by the cell counting kit-8 （CCK-8） method， the expression of SIRT6， PARP1， p16， p21， p53， proliferating cell nuclear antigen （PCNA）， deoxyribonucleic acid （DNA）-damaged protein γ-H2AX was detected by Western blot， and VSMC proliferation was detected by EdU staining. The silenced VSMCs were prepared by siRNA-SIRT6 transfection， and the protein expressions of SIRT6， PARP1， p16， and γ-H2AX in VSMCs silenced by SIRT6 were observed. ResultThe results of SA-β-Gal staining showed that the senescence positive rate of SA-β-Gal staining in the model group was higher than that in the normal group （P<0.01）， and the positive rate of SA-β-Gal staining in the Pae group was significantly lower than that in the model group （P<0.05， P<0.01）. The results of Western blot showed that as compared with the normal group， the expression of PCNA， SIRT6， and PARP1 in the model group was down-regulated， and the expression of aging-related proteins p16， p21， p53， and γ-H2AX was up-regulated in the model group （P<0.05， P<0.01）. Compared with the model group， Pae promoted the protein expression of PCNA， SIRT6， and PARP1 and inhibited the protein expression of p16， p21， p53， and γ-H2AX in a dose-dependent manner （P<0.05， P<0.01）. The results of EdU staining showed that the number of EdU positive cells in the model group was lower than that in the normal group （P<0.01）， and the number of EdU positive cells in Pae groups was significantly higher than that in the model group （P<0.05， P<0.01）. After SIRT6 silencing， the effects of Pae on promoting SIRT6 and PARP1 and inhibiting P16 were reversed （P<0.05， P<0.01）. In addition， the addition of SIRT6 inhibitor （IN-1） promoted the occurrence of cell senescence induced by AngⅡ （P<0.05， P<0.01）. ConclusionPae can effectively inhibit the aging of VSMCs， and its mechanism may be related to the regulation of SIRT6/PARP1 signal pathway.

Gut microbiota dysbiosis is an avenue for the promotion of atherosclerosis (AS) and this effect is mediated partly via the circulating microbial metabolites. More microbial metabolites related to AS vascular inflammation, and the mechanisms involved need to be clarified urgently. Paeonol (Pae) is an active compound isolated from Paeonia suffruticoas Andr. with anti-AS inflammation effect. However, considering the low oral bioavailability of Pae, it is worth exploring the mechanism by which Pae reduces the harmful metabolites of the gut microbiota to alleviate AS. In this study, ApoE^-/- mice were fed a high-fat diet (HFD) to establish an AS model. AS mice were administrated with Pae (200 or 400 mg·kg^-1) by oral gavage and fecal microbiota transplantation (FMT) was conducted. 16S rDNA sequencing was performed to investigate the composition of the gut microbiota, while metabolomics analysis was used to identify the metabolites in serum and cecal contents. The results indicated that Pae significantly improved AS by regulating gut microbiota composition and microbiota metabolic profile in AS mice. We also identified α-hydroxyisobutyric acid (HIBA) as a harmful microbial metabolite reduced by Pae. HIBA supplementation in drinking water promoted AS inflammation in AS mice. Furthermore, vascular endothelial cells (VECs) were cultured and stimulated by HIBA. We verified that HIBA stimulation increased intracellular ROS levels, thereby inducing VEC inflammation via the TXNIP/NLRP3 pathway. In sum, Pae reduces the production of the microbial metabolite HIBA, thus alleviating the ROS/TXNIP/NLRP3 pathway-mediated endothelial inflammation in AS. Our study innovatively confirms the mechanism by which Pae reduces the harmful metabolites of gut microbiota to alleviate AS and proposes HIBA as a potential biomarker for AS clinical judgment.
Animals ; Mice ; Atherosclerosis/drug therapy* ; Diet, High-Fat ; Endothelial Cells ; Inflammation/drug therapy* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Reactive Oxygen Species

ObjectiveThis study aimed to investigate the HIV genotypic subtypes and molecular transmission clusters among men who have sex with men （MSM） with newly reported HIV infections in Dehong Dai and Jingpo Autonomous Prefecture （Dehong Prefecture）， Yunnan Province， China， between 2010 and 2019. The study aimed to identify potential high-risk transmitters and provide reference data for screening， management， and intervention of infection sources. MethodsPlasma samples from newly reported HIV-positive MSM individuals in Dehong Prefecture between 2010 and 2019 were collected. The viral pol gene fragments were amplified， sequenced， and genotyped. Genetic distances （GD） between pairwise sequences were analyzed and calculated. MEGA 7.0 and Gephi were used for phylogenetic and molecular transmission network analysis. ResultsA total of 159 newly reported HIV infections among MSM were included in the study， with successful genotyping of 100 cases. Nine HIV-1 subtypes were identified， with the most prevalent being CRF01_AE subtype （52%）， followed by CRF07_BC subtype （31%）， CRF55_01B subtype （10%）， and others （7%）. Cluster analysis revealed a total network access rate of 67%， forming three transmission clusters. CRF01_AE subtype formed two transmission clusters with 38 and 3 infected individuals， while CRF07_BC subtypes formed one transmission cluster with 26 infected individuals. The transmission network within the CRF01_AE clusters exhibited a more complex relationship. Significant differences in educational level were observed between the two main transmission clusters. ConclusionThe predominant HIV subtypes among newly reported MSM cases in Dehong Prefecture between 2010 and 2019 were CRF01_AE and CRF07_BC. Significant cultural differences are observed between the main transmission clusters. Continued monitoring of genotypic subtypes and targeted interventions within transmission clusters are warranted.

Objective To establish a blast injury experimental model using a shock tube at lateral lying position of C57BL/6 mice, investigate biomechanical responses of macrophages/microglia cells in the heart, lung and brain tissues to mechanical damage by shock wave within 24 hours. Methods Shock tube was employed to generate a shock wave to C57BL/6 mice. Firstly, the weight changes of mice were measured at different time points after the shock. Then the cardiac, pulmonary and whole brain tissue samples were dissected after anesthesia. Pathological sections were stained with HE staining to detect structural damage; the TUNEL staining method was used to mark and count the proportion of dead cells in each tissue. Microglial cells were labeled with fluorescent antibody, while responses and changes of macrophages/microglia after shock loading were analyzed. Results The shock tube exerted 179 kPa overpressure shock wave upon sideway of the mouse, and lethal rate of the mouse was 3.33%. Compared with normal control group, the mice in experimental group had a significant weight loss within 24 hours after loading shock. Pathological sections showed rupture of lung tissues after shock, accompanied by alveolar protein deposition, pulmonary bulla and other diseases. Fluorescence staining showed that lung tissue was recruited and activated in a large amount within 24 hours. The proportion of dead cells cleared rebounded to normal level within 24 hours. The heart was highly tolerant to shock, and macrophages appeared near the large blood vessels. The brain showed unilateral aggregation of microglia due to the impact posture, mainly due to prolonged inflammation and a higher proportion of dead cells at the junction of gray and white matter. Conclusions A blast shock model at lateral lying position of the mouse was established. Within 24 hours, macrophages/microglia were recruited quickly to the injury site after being impacted, which mediated strong immune stress, and might participate in the immune response to trigger a second long-term inflammatory injury. The results of the study provide experimental basis for the evaluation of primary impact injury, such as dose-effect relationship and tissue damage difference.

Objective: To explore the treatment technique, occurrence and development patterns of such radiation injuries as in a major radiological accident in which a victim suffered mild bone marrow radiation sickness combined grade degree Ⅲ acute radiation induced skin injury, based on his dose estimation, clinical manifestations and disease treatments. Methods: History inquiry in detail, earlier physical dose estimation and biological dose estimation were conducted in conjunction with analyzing the chromosome aberration of peripheral blood lymphocytes. The physical dose was estimated by Monte Carlo method.The systematic laboratory and imaging examination was performed to evaluate the condition. The comprehensive analysis was conducted to determine the diagnosis and treatment plan. Results: At 3d after the exposure, "Ren" felt mild pain and discomfortable on the skin of the right index finger. The body of the right hand index finger was covered with blister at 21 d after exposure.The estimation of biological dose was 0.43 Gy (95%CI: 0.31-0.58 Gy), and the physical dose was estimated to be 36-164 Gy for each part of the right hand finger. The hematopoietic system, immune system and endocrine system were normal. The liver function index value was transiently increased. The liver damage resulted from the use of antibiotic-induced combined with the patient′s past medical history and admission examination result, and the relevant antibiotics were discontinued. The liver function returned to normal after liver protection treatment. At 22 d after irradiation, a right finger incision and decompression surgery were performed. The stem cells were extracted and implanted into the right index finger. After 59 days of hospitalization, there was no obvious discomfort in the body, and the right index finger recovered well, as well as the pain significantly relieved, and the knuckle activity was basically normal. Conclusions The patient with excessive radiation and grade Ⅲ acute radiation skin injury was successfully treated, and local application of autologous adipose-derived stem cell transplantation achieved good result .

Objective To investigate the clinicopathological characteristics and prognostic factors of hepatoid adenocarcinoma of the stomach (HAS).Methods From Jan 2006 to Jan 2016,the clinical pathological data of 15 HAS cases in our hospital were analyzed retrospectively.60 TNM stage matched cases of non-HAS gastric cancer served as the control group.The clinical pathology factors and prognosis were compared between the two groups.Results Serum AFP positive HAS patients accounted for 87％.The serum level of AFP in HAS were significantly higher than that in controls (P ＜0.001).HAS was more prone to lymphatic invasion (73％ vs.33％,x2 =7.918,P =0.005) and vascular invasion (40％ vs.10％,x2 =8.036,P =0.005) than control gastric cancer.The immunohistochemistry positive rates of AFP,Glypican3,Hepatocyte and CEA in HAS were 87％,87％,33％,53％ respectively.Liver metastasis (53％ vs.12％,P =0.001) and other distant metastases (53％ vs.15％,P =0.004) were higher in the HAS.HAS median survival time was significantly lower (28.0 months vs.50.7 months,x2 =4.350,P =0.037).Postoperative HAS 1,3 and 5 years survival rates were 80％,33％ and 20％,respectively,significantly worse than 97％,78％ and 33％ in control group (x2 =5.525,17.198,5.472,P =0.019,0.000,0.019 respectively).The independent risk factor influencing the prognosis of HAS included TNM stage,vascular invasion,distant metastasis.Conclusions HAS is often complicated with higher serum AFP and prone to vascular invasion,lymph node metastasis and distant metastasis,hence a poorer prognosis.

Objective To investigate a dose response curve based on a genetic workstation with automatic analysis system of dicentric chromosome assay (DCA) for establishing a high speed dose estimation method.Methods Peripheral blood from three healthy volunteers was irradiated in vitro using 60Co γ-rays,and then lymphocytes were cultured and fixed on slides using the standard protocol for DCA.Dicentric chromosome in metaphase cells was analyzed automatically with the genetic workstation and confirmed manually,and the dose response curve of automated dicentric chromosome was fitted.Dicentric chromosome of another peripheral blood sample irradiated with different doses was manually analyzed to verify the accuracy of the above automated DCA.Results The yield of automated DCA was well fitted by an equation Y =0.018 06D2 + 0.012 79D + 0.000 489 1 with a correlation coefficient R2 =0.961.The biological dose of radiation could be accurately estimated by this dose response curve within a few minutes.Conclusions We had successfully established a new dosimetry method by analyzing dicentric chromesome automatically,which can save a lot of manual analysis time and hence has important significance for emergency rescue in nuclear accidents.