Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc), primarily manifesting as motor dysfunctions such as resting tremor, muscle rigidity, and bradykinesia. According to the classical model of basal ganglia motor control, approximately half of the medium spiny neurons (MSNs) in the striatum are D1-MSNs, which constitute the direct pathway. These neurons express D₁-dopamine receptor (D₁R) and substance P, and they mainly participate in the selection, initiation, and execution of movements. The other half are D2-MSNs, which constitute the indirect pathway. These neurons express D₂-dopamine receptor (D₂R) and adenosine 2A receptors and are involved in inhibiting unnecessary movements or terminating ongoing movements, thereby adjusting movement sequences to perform more precise motor behaviors. The direct pathway in the striatum modulates the activity of motor cortex neurons by exciting D1-MSNs through neurotransmitters such as glutamate (Glu), allowing the motor cortex to send signals more freely to the motor system, thus facilitating the generation and execution of specific motor behaviors. Studies using D1-Cre and D2-Cre mice with neurons labeled for D₁R and D₂R have shown that both types of neurons are involved in the execution of movements, with D1-MSNs participating in movement initiation and D2-MSNs in inhibiting actions unrelated to the target movement. These findings suggest that the structural and functional plasticity of D1-MSNs and D2-MSNs in the basal ganglia circuitry enables motor learning and behavioral regulation. Additionally, when SNpc DA neurons begin to degenerate, D1-MSNs are initially affected but do not immediately cause motor impairments. In contrast, when D2-MSNs undergo pathological changes, they are first activated by upstream projecting neurons, leading to the inhibition of most motor behaviors and resulting in motor dysfunction. Therefore, it is hypothesized that motor impairments such as bradykinesia and initiation difficulties are more closely related to the functional activity of D2-MSNs. The extracellular signal-regulated kinase (Erk)/mitogen-activated protein kinase (MAPK) signaling pathway has been identified as a critical modulator in the pathophysiology of PD. Recent findings indicate that Erk/MAPK signaling pathway can mediate DA and Glu signaling in the central nervous system, maintaining normal functional activity of striatal MSNs and influencing the transmission of motor control signals. Within this complex regulatory network, the Erk/MAPK signaling pathway plays a key role in transmitting motor information to downstream neurons, regulating normal movements, avoiding unnecessary movements, and finely tuning motor behaviors. Our laboratory’s previous research found that 4 weeks of aerobic exercise intervention improved motor dysfunction in PD mice by inhibiting the Erk1/2 signaling upstream of striatal MSNs, primarily involving the Erk1/2 signaling in D2-MSNs rather than D1-MSNs. This review summarizes the neurobiological mechanisms of Erk/MAPK signaling pathway in D2-MSNs for the prevention and treatment of motor dysfunction in PD. By exploring the role of this signaling pathway in regulating motor abnormalities and preventing motor dysfunction in the central nervous system of PD, this review provides new theoretical perspectives for related mechanistic research and therapeutic strategies.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Central venous lesion represents one of the common complications affecting vascular access in hemodialysis patients, potentially compromising hemodialysis efficacy. The management of symptomatic central venous lesion remains a critical challenge in clinical practice. Current primary treatment strategies include percutaneous transluminal angioplasty and percutaneous transluminal stenting. Advances in techniques such as sharp recanalization and the mother-child platform approach, along with the development of high-pressure balloons, paclitaxel- coated balloons, and covered stents, have significantly improved procedural success rates. However, unresolved issues persist, including standardized treatment protocols, technical considerations for lesion traversal, and optimal stent selection criteria. This article comprehensively reviews the treatment principles, lesion passage techniques, treatment techniques, and recent advancements of central venous lesion.

This article retrospectively analyzed the clinical data of three recipients who developed acute antibody mediated rejection (AMR) after receiving different courses of immunotherapy prior to liver transplantation for hepatocellular carcinoma. It focused on their diagnostic and therapeutic processes, including the immunosuppressive induction regimen [rabbit anti-human thymocyte globulin (rATG) + methylprednisolone] , postoperative liver function changes, diagnostic methods for acute AMR (such as allograft liver biopsy, panel reactive antibody testing, and donor-specific antibody testing) , and the combination treatment strategies used (rATG, rituximab, intravenous immunoglobulin, and plasma exchange). The aim of this article is to summarize the clinical characteristics, diagnosis, and treatment experiences of acute AMR occurring after liver transplantation in patients with liver cancer who had received immunotherapy, explore the potential risks involved, and provide a reference for clinicians in managing such cases.

Central venous lesion represents one of the common complications affecting vascular access in hemodialysis patients, potentially compromising hemodialysis efficacy. The management of symptomatic central venous lesion remains a critical challenge in clinical practice. Current primary treatment strategies include percutaneous transluminal angioplasty and percutaneous transluminal stenting. Advances in techniques such as sharp recanalization and the mother-child platform approach, along with the development of high-pressure balloons, paclitaxel- coated balloons, and covered stents, have significantly improved procedural success rates. However, unresolved issues persist, including standardized treatment protocols, technical considerations for lesion traversal, and optimal stent selection criteria. This article comprehensively reviews the treatment principles, lesion passage techniques, treatment techniques, and recent advancements of central venous lesion.

This article retrospectively analyzed the clinical data of three recipients who developed acute antibody mediated rejection (AMR) after receiving different courses of immunotherapy prior to liver transplantation for hepatocellular carcinoma. It focused on their diagnostic and therapeutic processes, including the immunosuppressive induction regimen [rabbit anti-human thymocyte globulin (rATG) + methylprednisolone] , postoperative liver function changes, diagnostic methods for acute AMR (such as allograft liver biopsy, panel reactive antibody testing, and donor-specific antibody testing) , and the combination treatment strategies used (rATG, rituximab, intravenous immunoglobulin, and plasma exchange). The aim of this article is to summarize the clinical characteristics, diagnosis, and treatment experiences of acute AMR occurring after liver transplantation in patients with liver cancer who had received immunotherapy, explore the potential risks involved, and provide a reference for clinicians in managing such cases.

Objective To investigate the intervention efficacy of best possible self (BPS)on the mental health of new recruits (including state optimism and pessimism,perceived stress and subjective well-being).Methods A non-randomized controlled trial was conducted on 212 new recruits subjected with cluster sampling from an army unit in a training base for new recruits in September 2023.Based on their organizational structure,they were divided into a study group (n=100,receiving BPS intervention 15 min/d,for 2 consecutive weeks)and a control group[n=112,typical day (TD)intervention,15 min/d,same period].Future Expectancy Scale (FEX),Chinese Perceived Stress Scale (CPSS),Positive and Negative Affect Scale (PANAS ) and Satisfaction with Life Scale (SWLS ) were used to measure the 2 groups of participants at T0 (baseline),T1 (end of the first week of intervention),T2 (end of the second week of intervention)and T3 (1 week after the end of intervention)in order to evaluate the intervention efficacy on above mentioned mental health indicators.Results There were no significant differences in demographic and baseline psychological variables listed above between the 2 groups.However,as the training progressed,obvious differences were observed in the training effects on state pessimism,perceived stress and subjective well-being (including affective and cognitive well-being)between them.When compared with the baseline data (T0),the study group had notably reduced state pessimism (P<0.01)and elevated affective (P<0.001) and cognitive well-being (P<0.001)during T1 and T3,and decreased perceived stress at T1 (P<0.05)and T3 (P<0.001).However,no such changes of above indicators were observed in the control group before and after training.Conclusion A 2-week BPS intervention can effectively reduce state pessimism and perceived stress,promote subjective well-being,and improve mental health in new recruits during new recruit training.