Important forensic diagnostic indicators of sudden death in coronary atherosclerotic heart dis-ease,such as acute or chronic myocardial ischemic changes,sometimes make it difficult to locate the ischemic site due to the short death process,the lack of tissue reaction time.In some cases,the de-ceased died of sudden death on the first-episode,resulting in difficulty for medical examiners to make an accurate diagnosis.However,clinical studies on coronary instability plaque revealed the key role of coronary spasm and thrombosis caused by their lesions in sudden coronary death process.This paper mainly summarizes the pathological characteristics of unstable coronary plaque based on clinical medi-cal research,including plaque rupture,plaque erosion and calcified nodules,as well as the influencing factors leading to plaque instability,and briefly describes the research progress and technique of the atherosclerotic plaques,in order to improve the study on the mechanism of sudden coronary death and improve the accuracy of the forensic diagnosis of sudden coronary death by diagnosing different patho-logic states of coronary atherosclerotic plaques.

Objective To explore the effects of different concentrations of lidocaine infiltration and analgesia in pleural cavity after lung cancer surgery on rehabilitation of patients.Methods A total of 86 patients with lung cancer were selected and divided into the high concentration group(43 cases)and low concentration group(43 cases)by random number table method.Patients in the high concentration group received injection of 2.0%lidocaine hydrochloride in pleural cavity through the epidural catheter 1st day after surgery,and patients in the low concentration group received injection of 1.5%lidocaine hydrochloride in pleural cavity.In addition,patients in the two groups were treated with patient-controlled intravenous analgesia after surgery.The first time of getting out of bed,first time of exhaustion,first time of defecation and hospital stay after surgery of the two groups were compared.The visual analogue scale(VAS)scores 6 hours,12 hours,24 hours and 48 hours after surgery,the occurrence of agitation during the postoperative awakening period,and the number of analgesic pump compressions and the dosage of analgesic drugs within 24 hours after surgery were compared.The incidence of adverse drug reactions 24 hours after surgery were recorded and the quality of recovery of patients 24 hours after surgery was evaluated by 40-item quality of recovery score(QoR-40).Results The first time of getting out of bed,first time of exhaustion,first time of defecation and hospital stay after operation of patients in the high concentration group were shorter than those in the low concentration group(P<0.05).The VAS scores of the two groups 12 hours and 24 hours after surgery were higher than those 6 hours after surgery(P<0.05),the VAS scores 24 hours and 48 hours after surgery were lower than those 12 hours after surgery(P<0.05),and the VAS scores 48 hours after surgery were lower than those 24 hours after surgery(P<0.05).The VAS scores 6 hours,12 hours,24 hours,and 48 hours after surgery of patients in the high concentration group were lower than those in the low concentration group(P<0.05).The occurrence of agitation during the postoperative awakening period,and the number of analgesic pump compressions and the dosage of analgesic drugs within 24 hours after surgery for patients in the high concentration group were lower/less than those in the low concentration group(P<0.05).There was no significant difference in the total incidence of adverse drug reactions between the two groups(P>0.05).The total QoR-40 score of patients in the high concentration group were higher than those in the low concentration group(P<0.05).Conclusion The use of 2.0%lidocaine infiltration and analgesia in pleural cavity for patients after lung cancer surgery can reduce the agitation during the awakening period,alleviate the postoperative pain,improve the quality of postoperative recovery,and promote the postoperative recovery of the patients,with certain safety.

Parkinson’s disease (PD) is a neurodegenerative disease characterized by various motor and non-motor symptoms. The complexity of its symptoms suggests that PD is a heterogeneous neurological disorder. Its pathological changes are not limited to the substantia nigra-striatal system, but gradually extending to other regions including the cerebellum. The cerebellum is connected to a wide range of central nervous system regions that form essential neural circuits affected by PD. In addition, altered dopaminergic activity and α-synuclein pathology are found in the cerebellum, further suggesting its role in the PD progression. Furthermore, an increasing evidence obtained from imaging studies has demonstrated that cerebellar structure, functional connectivity, and neural metabolism are altered in PD when compared to healthy controls, as well as among different PD subtypes. This review provides a comprehensive summary of the cerebellar pathophysiology and results from neuroimaging studies related to both motor and non-motor symptoms of PD, highlighting the potential significance of cerebellar assessment in PD diagnosis, differential diagnosis, and disease monitoring.

Objective To analyze the clinical characteristics of high energy metabolism in lung cancer patients and its correlation with body composition,nutritional status,and quality of life,and to develop a corresponding risk prediction model.Methods Retrospectively analyzed 132 primary lung cancer patients admitted to the First Hospital of Shanxi Medical University from January 2022 to May 2023,and categorized into high(n=94)and low energy metabolism group(n=38)based on their metabolic status.Differences in clinical data,body composition,Patient Generated Subjective Global Assessment(PG-SGA)scores,and European Organization for Research and treatment of Cancer(EORTC)Quality of Life Questionnaire-Core 30(QLQ-C30)scores were compared between the two groups.Logistic regression was used to identify the risk factors for high energy metabolism in lung cancer patients,and a risk prediction model was established accordingly;the Hosmer-Lemeshow test was used to assess the model fit,and the ROC curve was used to test the predictive efficacy of the model.Results Of the 132 patients with primary lung cancer,94(71.2%)exhibited high energy metabolism.Compared with low energy metabolism group,patients in high-energy metabolism group had a smoking index of 400 or higher,advanced disease staging of stage Ⅲ or Ⅳ,and higher levels of IL-6 level,low adiposity index,low skeletal muscle index,and malnutrition(P<0.05),and lower levels of total protein,albumin,hemoglobin level,and prognostic nutritional index(PNI)(P<0.05).There was no significant difference in age,gender,height,weight,BMI and disease type between the two groups(P>0.05).Logistic regression analysis showed that smoking index≥400,advanced disease stage,IL-6≥3.775 ng/L,and PNI<46.43 were independent risk factors for high energy metabolism in lung cancer patients.The AUC of the ROC curve for the established prediction model of high energy metabolism in lung cancer patients was 0.834(95%CI 0.763-0.904).Conclusion The high energy metabolic risk prediction model of lung cancer patients established in this study has good fit and prediction efficiency.

Pathological,electrophysiological,and neuroimaging changes in the cerebellum can occur in neurodegenerative diseases such as Alzheimer disease,Parkinson disease,and amyotrophic lateral sclerosis.The activation and neurodegeneration of neurons in specific cerebellar regions may contribute to the clinical symptoms and pathological processes of these neurodegenerative diseases.This article reviews the clinical assessment methods and neuroimaging studies related to cerebellar symptoms in neurodegenerative diseases.The findings suggest that structural and functional abnormalities of the cerebellum are associated with symptoms such as motor,cognitive,and emotional dysfunction in these diseases.Developing a multidimensional,systematic clinical and imaging evaluation approach centered on the cerebellum will help deepen our understanding of the cerebellum's role in the pathogenesis of neurodegenerative diseases.It will also provide new directions for the early identification of symptoms,differential diagnosis,and the formulation of precise treatment plans.

Objective To investigate the contribution of microglia in the basolateral amygdala(BLA)to pain hypersensitivity and pain-related aversion in knee-joint monoarthritis mice.Methods A total of 61 mice were used for behavioral tests(14 mice in the control group and 47 mice in the model group),and other 6 mice were used for cell morphology(3 mice in each group).An animal model of knee-joint monoarthritis was established by injection of complete Freund's adjuvant(CFA)into the knee-joint cavity of mice.The von Frey and Hargreaves tests were used to examine mechanical allodynia and thermal hyperalgesia in mice,respectively.The place escape/avoidance paradigm test was used to examine pain-related aversion.Open field test and elevated plus maze test were used to examine anxiety-like behaviors in mice.Morphological changes of microglia in the BLA area after CFA injection were assessed by 3D reconstruction of microglia in the BLA brain region using immunofluorescence staining and Imaris software.Results Compared with the control group,CFA-arthritic mice produced significant mechanical and thermal hyperalgesia in the ipsilateral hindpaw and maintained for at least 12 and 19 days,respectively.Meanwhile,CFA injection induced pain-related aversion and anxiety-like behaviors in mice,accompanied by significant activation of BLA microglia.Inhibition of BLA microglia activation alleviated CFA-induced hyperalgesia and aversive behaviors but had no significant effects on anxiety-like behaviors.Conclusion CFA-arthritic mice produce hyperalgesia,pain-related aversion,and anxious behavior,in which hyperalgesia and pain-related aversion may be mediated by the activation of microglia in BLA.

Objective To analyze the screening results of spinal problems in children and adolescents aged 6-18 years and the influencing factors of scoliosis to provide reference for the prevention of spinal problems in children and adolescents. Methods Stratified cluster random sampling was used to screen the prevalence of scoliosis among kindergarten to senior high school students in Shiyan city, and a questionnaire survey was conducted among subjects or parents. Multivariate logistic regression was used to analyze the risk factors affecting the occurrence of scoliosis. Results A total of 1 674 children and adolescents were investigated, and 113 cases of scoliosis were detected, with a detection rate of 6.75%. The probability of scoliosis was 1.92% (13/678), 5.35% (28/523) and 17.76% (72/473) in elementary school, junior high school and senior high school students, respectively. The detection rate of scoliosis gradually increased with the increase of education level (χ² for trend = 5.272, P < 0.05). In the scoliosis group, the proportions of females (65.49%), malnutrition (25.66%), sitting postural irregularity (52.21%), daily sitting learning time > 12 h (63.72%), daily electronic product use time > 2 h (67.26%), high physical activity > 1 time/d (42.48%) in the past 7 d, and daily outdoor activity time ≤ 2 h (62.83%) were higher than those in the group without scoliosis (P < 0.05).Multivariate logistic regression analysis showed that female students (OR=1.840, 95% CI:1.385-2.716), malnutrition (OR=2.175, 95% CI: 1.542-3.941), improper sitting posture (OR=2.228, 95% CI: 1.592-4.182), daily sitting study time>12 hours (OR=3.258 , 95% CI: 2.562-11.247), daily electronic product use time>2 hours (OR=2.619, 95% CI: 1.935-5.508) , Heavy physical activity in the past 7 days (OR=1.724, 95% CI: 1.347-2.966) , Daily outdoor activity ≤2 h（OR=1.830，95% CI: 1.463-3.103）is a risk factor for scoliosis in children and adolescents (P<0.05). Conclusions The occurrence of scoliosis in children and adolescents is related to gender, nutritional status, and learning habits, and it is necessary to strengthen the screening of high-risk groups in order to reduce the occurrence of scoliosis.

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.

Mutations in genes encoding amyloid precursor protein (APP) and presenilins (PSs) cause familial forms of Alzheimer's disease (AD), a neurodegenerative disorder strongly associated with aging. It is currently unknown whether and how AD risks affect early brain development, and to what extent subtle synaptic pathology may occur prior to overt hallmark AD pathology. Transgenic mutant APP/PS1 over-expression mouse lines are key tools for studying the molecular mechanisms of AD pathogenesis. Among these lines, the 5XFAD mice rapidly develop key features of AD pathology and have proven utility in studying amyloid plaque formation and amyloid β (Aβ)-induced neurodegeneration. We reasoned that transgenic mutant APP/PS1 over-expression in 5XFAD mice may lead to neurodevelopmental defects in early cortical neurons, and performed detailed synaptic physiological characterization of layer 5 (L5) neurons from the prefrontal cortex (PFC) of 5XFAD and wild-type littermate controls. L5 PFC neurons from 5XFAD mice show early APP/Aβ immunolabeling. Whole-cell patch-clamp recording at an early post-weaning age (P22-30) revealed functional impairments; although 5XFAD PFC-L5 neurons exhibited similar membrane properties, they were intrinsically less excitable. In addition, these neurons received smaller amplitude and frequency of miniature excitatory synaptic inputs. These functional disturbances were further corroborated by decreased dendritic spine density and spine head volumes that indicated impaired synapse maturation. Slice biotinylation followed by Western blot analysis of PFC-L5 tissue revealed that 5XFAD mice showed reduced synaptic AMPA receptor subunit GluA1 and decreased synaptic NMDA receptor subunit GluN2A. Consistent with this, patch-clamp recording of the evoked L23>L5 synaptic responses revealed a reduced AMPA/NMDA receptor current ratio, and an increased level of AMPAR-lacking silent synapses. These results suggest that transgenic mutant forms of APP/PS1 overexpression in 5XFAD mice leads to early developmental defects of cortical circuits, which could contribute to the age-dependent synaptic pathology and neurodegeneration later in life.
Mice ; Animals ; Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Amyloid beta-Protein Precursor/metabolism* ; Mice, Transgenic ; Neurons/metabolism* ; Receptors, AMPA/metabolism* ; Disease Models, Animal

Parkinson's disease (PD) is a common neurodegenerative disorder caused by the loss of dopamine neurons in the substantia nigra and the formation of Lewy bodies, which are mainly composed of alpha-synuclein fibrils. Alpha-synuclein plays a vital role in the neuroinflammation mediated by the nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in PD. A better understanding of the NLRP3 inflammasome-mediated neuroinflammation and the related mitochondrial impairment during PD progression may facilitate the development of promising therapies for PD. This review focuses on the molecular mechanisms underlying NLRP3 inflammasome activation, comprising priming and protein complex assembly, as well as the role of mitochondrial impairment and its subsequent inflammatory effects on the progression of neurodegeneration in PD. In addition, the therapeutic strategies targeting the NLRP3 inflammasome for PD treatment are discussed, including the inhibitors of NLRP3 inflammatory pathways, mitochondria-focused treatments, microRNAs, and other therapeutic compounds.
Humans ; Parkinson Disease/complications* ; alpha-Synuclein ; Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; Neuroinflammatory Diseases ; Mitochondria