Background: and Purpose Essential tremor with a midline distribution (Mid-ET) may represent a distinct subtype of essential tremor (ET) that primarily affects midline structures, often indicating advanced disease stage and increased severity. Recent studies have highlighted the complexity of Mid-ET, but research on neurological soft signs (NSS) in Mid-ET remains insufficient. Methods: The patients with ET included in this cross-sectional study were divided into two subgroups based on whether or not the ET had a midline distribution: Mid-ET and No-MidET. Comparative analyses were performed to assess clinical features and NSS prevalence in these subgroups. Results: Among 1,160 patients, 567 (48.9%) were Mid-ET and 593 (51.1%) were No-Mid-ET.The prevalence rates of head, face (including the jaw), and voice tremors were 31.9%, 23.0%, and 25.8%, respectively. In Mid-ET, tremor often affects multiple midline structures simultaneously. In the entire cohort, 24.7%, 16.6%, and 7.6% of patients exhibited tremors in one, two, and three midline structures, respectively. The prevalence of common NSS, including mild cognitive impairment, impaired tandem gait, and questionable dystonic posturing, was significantly higher in the Mid-ET than the No-Mid-ET subgroup (all p<0.001). Furthermore, we found that female sex (p<0.001), olfactory dysfunction (p=0.003), and questionable dystonic posturing (p=0.004) were associated with Mid-ET. Conclusions Mid-ET and No-Mid-ET presented significant clinical differences. The presence of questionable dystonic posturing may contribute to the distinct characteristics of Mid-ET, suggesting the presence of pathophysiological differences between the subgroups. Further investigations are warranted to determine the potential pathophysiological link between NSS and Mid-ET.

Background: and Purpose Essential tremor with a midline distribution (Mid-ET) may represent a distinct subtype of essential tremor (ET) that primarily affects midline structures, often indicating advanced disease stage and increased severity. Recent studies have highlighted the complexity of Mid-ET, but research on neurological soft signs (NSS) in Mid-ET remains insufficient. Methods: The patients with ET included in this cross-sectional study were divided into two subgroups based on whether or not the ET had a midline distribution: Mid-ET and No-MidET. Comparative analyses were performed to assess clinical features and NSS prevalence in these subgroups. Results: Among 1,160 patients, 567 (48.9%) were Mid-ET and 593 (51.1%) were No-Mid-ET.The prevalence rates of head, face (including the jaw), and voice tremors were 31.9%, 23.0%, and 25.8%, respectively. In Mid-ET, tremor often affects multiple midline structures simultaneously. In the entire cohort, 24.7%, 16.6%, and 7.6% of patients exhibited tremors in one, two, and three midline structures, respectively. The prevalence of common NSS, including mild cognitive impairment, impaired tandem gait, and questionable dystonic posturing, was significantly higher in the Mid-ET than the No-Mid-ET subgroup (all p<0.001). Furthermore, we found that female sex (p<0.001), olfactory dysfunction (p=0.003), and questionable dystonic posturing (p=0.004) were associated with Mid-ET. Conclusions Mid-ET and No-Mid-ET presented significant clinical differences. The presence of questionable dystonic posturing may contribute to the distinct characteristics of Mid-ET, suggesting the presence of pathophysiological differences between the subgroups. Further investigations are warranted to determine the potential pathophysiological link between NSS and Mid-ET.

Background: and Purpose Essential tremor with a midline distribution (Mid-ET) may represent a distinct subtype of essential tremor (ET) that primarily affects midline structures, often indicating advanced disease stage and increased severity. Recent studies have highlighted the complexity of Mid-ET, but research on neurological soft signs (NSS) in Mid-ET remains insufficient. Methods: The patients with ET included in this cross-sectional study were divided into two subgroups based on whether or not the ET had a midline distribution: Mid-ET and No-MidET. Comparative analyses were performed to assess clinical features and NSS prevalence in these subgroups. Results: Among 1,160 patients, 567 (48.9%) were Mid-ET and 593 (51.1%) were No-Mid-ET.The prevalence rates of head, face (including the jaw), and voice tremors were 31.9%, 23.0%, and 25.8%, respectively. In Mid-ET, tremor often affects multiple midline structures simultaneously. In the entire cohort, 24.7%, 16.6%, and 7.6% of patients exhibited tremors in one, two, and three midline structures, respectively. The prevalence of common NSS, including mild cognitive impairment, impaired tandem gait, and questionable dystonic posturing, was significantly higher in the Mid-ET than the No-Mid-ET subgroup (all p<0.001). Furthermore, we found that female sex (p<0.001), olfactory dysfunction (p=0.003), and questionable dystonic posturing (p=0.004) were associated with Mid-ET. Conclusions Mid-ET and No-Mid-ET presented significant clinical differences. The presence of questionable dystonic posturing may contribute to the distinct characteristics of Mid-ET, suggesting the presence of pathophysiological differences between the subgroups. Further investigations are warranted to determine the potential pathophysiological link between NSS and Mid-ET.

Objective To observe the clinical efficacy of toripalimab combined with bronchial ar-terial chemoembolization(BACE)and intensity-modulated radiotherapy(IMRT)in advanced lung cancer.Methods A prospective single-arm trial was conducted in 104 patients with programmed death-ligand 1(PD-L1)-positive,driver gene-negative non-small cell lung cancer(NSCLC)in stages of Ⅲ B to Ⅳ admitted to the First People's Hospital of Guangyuan City of Sichuan Province.All patients received toripalimab combined with BACE and IMRT.Clinical efficacy,symptom improve-ment time,tumor biomarker levels[carcinoembryonic antigen(CEA),carbohydrate antigen 199(CA199),cytokeratin 19 fragment(CYFRA21-1),neuron-specific enolase(NSE)],T-lymphocyte subsets(CD3+,CD4+,CD4+/CD8+),survival outcomes,and adverse events were analyzed.Results Among 102 patients,the objective response rate(ORR)was 75.49％,disease control rate(DCR)was 90.20％,survival rate was 68.63％,and 12-month progression-free survival rate was 62.75％.The overall incidence of adverse events of any grade was 72.55％.Post-BACE,post-IMRT,and post-toripalimab treatment levels of CEA,CYFRA21-1,CA199,and NSE were significantly lower than baseline data(P＜0.05),with the lowest levels observed after toripalimab treatment compared to post-BACE and post-IMRT(P＜0.05).CD3+,CD4+,and CD4+/CD8+decreased after BACE,IMRT and toripalimab therapy,but they were increased following toripalimab therapy compared with the other two therapies(P＜0.05).Conclusion Toripalimab combined with BACE and IMRT demonstrates significant clinical efficacy and acceptable tolerability in PD-L1-positive,driver gene-negative NSCLC in stages of ⅢB to Ⅳ,serving as a preferred consolidation regimen after unresect-able chemoradiotherapy.

Objective To explore the neuroprotective effect of coenzyme Q10 and its possible mechanism in mice with chronic restraint stress(CRS).Methods Mouse models of CRS were treated with intraperitoneal injections of coenzyme Q10 at low,moderate and high doses(50,100 and 200 mg/kg,respectively,n=8),VX765(a caspase-1 specific inhibitor,50 mg/kg,n=8),or fluoxetine(10 mg/kg,n=8)on a daily basis for 4 weeks,and the changes in depression-like behaviors of the mice were assessed by sugar water preference test,forced swimming test and tail suspension test.The expression of glial fibrillary acidic protein(GFAP)in the hippocampus of the mice was detected using immunohistochemistry,and the number of synaptic spines was determined with Golgi staining.Western blotting was performed to detect the changes in the expressions of GFAP and pyroptosis-related proteins in the hippocampus,and the colocalization of neurons and caspase-1 p10 was examined with immunofluorescence assay.Results Compared with the normal control mice,the mouse models of CRS showed significantly reduced sugar water preference and increased immobility time in forced swimming and tail suspension tests(P<0.05),and these depression-like behaviors were obviously improved by treatment with coenzyme Q10,VX765 or FLX.The mouse models showed a significantly decreased positive rate of GFAP and lowered GFAP protein expression in the hippocampus with obviously decreased synaptic spines,enhanced expressions of GSDMD-N,caspase-1 and IL-1β,and increased colocalization of neurons and caspase-1 p10(all P<0.05).All these changes were significantly ameliorated in the mouse models after treatment with Q10.Conclusion Coenzyme Q10 can alleviate depression-like behaviors in mice with CRS by down-regulating the pyroptosis signaling pathway.

Objective:To explore the effects of type D personality on mild cognitive dysfunction (MCI) in patients with coronary heart disease and the multiple mediating roles of dietary inflammation index (DII) and systemic immune inflammation index (SII) between type D personality and MCI.Methods:A cross-sectional study was used. A total of 321 patients diagnosed with coronary heart disease by coronary angiography in the Second Affiliated Hospital of Harbin Medical University from May 2022 to March 2023 were selected as the study objects by convenient sampling method. General Information Questionnaire, Type-D Personality Scale-14, Montreal Cognitive Assessment, and Semi-Quantitative Food Frequency Questionnaire were employed for data collection. DII and SII were used to evaluate dietary inflammatory potential and systemic inflammatory status, respectively. Structural equation modeling was utilized to analyze the mediating effectsamong type D personality, DII, SII and MCI.Results:A total of 306 valid questionnaires were collected. Among the 306 patients, there were 215 males (70.3%) and 91 females (29.7%), aged 27-70 (59.24 ± 9.16) years old. The structural equation model showed that type D personality could directly influence MCI (effect size = - 1.098, 95% CI - 1.869 - - 0.327), and could also mediate the occurrence of MCI in coronary heart disease patients through the single mediation of DII (effect size = - 0.374, 95% CI - 0.644 - - 0.128) and SII (effect size = - 0.450, 95% CI - 0.806 - - 0.132), as well as the chain mediation of DII and SII (effect size = - 0.146, 95% CI - 0.293 - - 0.027). Conclusions:Type D personality, DII and SII can affect the occurrence of MCI in CHD patients, and DII and SII play multiple mediating roles between type D personality and MCI in patients with coronary heart disease. Clinical and community nurses can improve the unhealthy dietary behavior, reduce the level of inflammation and delay the occurrence and development of MCI by early screening of type D personality in patients with coronary heart disease.

Objective To explore the neuroprotective effect of coenzyme Q10 and its possible mechanism in mice with chronic restraint stress(CRS).Methods Mouse models of CRS were treated with intraperitoneal injections of coenzyme Q10 at low,moderate and high doses(50,100 and 200 mg/kg,respectively,n=8),VX765(a caspase-1 specific inhibitor,50 mg/kg,n=8),or fluoxetine(10 mg/kg,n=8)on a daily basis for 4 weeks,and the changes in depression-like behaviors of the mice were assessed by sugar water preference test,forced swimming test and tail suspension test.The expression of glial fibrillary acidic protein(GFAP)in the hippocampus of the mice was detected using immunohistochemistry,and the number of synaptic spines was determined with Golgi staining.Western blotting was performed to detect the changes in the expressions of GFAP and pyroptosis-related proteins in the hippocampus,and the colocalization of neurons and caspase-1 p10 was examined with immunofluorescence assay.Results Compared with the normal control mice,the mouse models of CRS showed significantly reduced sugar water preference and increased immobility time in forced swimming and tail suspension tests(P<0.05),and these depression-like behaviors were obviously improved by treatment with coenzyme Q10,VX765 or FLX.The mouse models showed a significantly decreased positive rate of GFAP and lowered GFAP protein expression in the hippocampus with obviously decreased synaptic spines,enhanced expressions of GSDMD-N,caspase-1 and IL-1β,and increased colocalization of neurons and caspase-1 p10(all P<0.05).All these changes were significantly ameliorated in the mouse models after treatment with Q10.Conclusion Coenzyme Q10 can alleviate depression-like behaviors in mice with CRS by down-regulating the pyroptosis signaling pathway.

Resection is one of the most important treatments for esophageal squamous cell carcinoma, and routine postoperative follow-up is an effective method for early detection and treatment of recurrent metastases, which can improve patients' quality of life and prognosis. This consensus aims to provide a reference for colleagues responsible for postoperative follow-up of esophageal squamous cell carcinoma patients in China, and further improve the standardization of the diagnosis and treatment of esophageal squamous cell carcinoma.

Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.