Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

Objective To provide basis for the formation of acute exacerbation of chronic obstructive pulmonary disease(AECOPD-STES),the item weight of the syndrome therapeutic evaluation scale for AECOPD-STES was determined.Methods Based on the clinical survey data of 387 AECOPD patients,the random forest method was adopted,and the Spyder integrated development environment.Anaconda navigator software was used to call the"random forest Classifier"in the sklearn package to establish the initial random forest model and calculate the item weights.Factor analysis was used to extract common factors with cumulative variance contribution>80%,and the item weight was calculated according to the cumulative variance contribution and component score coefficient of common factors.The percentage weight method was used to calculate the item weight based on the importance score of each item by 29 experts.Finally,40%,30%and 30%of the above three methods were given respectively to determine the final weight of the items.Results The random forest method showed that the weights of wind cold syndrome,cold Yin syndrome,phlegm heat syndrome,phlegm dampness syndrome and blood stasis syndrome were 0.014-0.170,0.076-0.194,0.017-0.183,0.010-0.183 and 0.069-0.298,respectively.Factor analysis showed that the weights of wind cold syndrome,cold yin Syndrome,phlegm heat syndrome,phlegm dampness syndrome and blood stasis syndrome were 0.030-0.111,0.100-0.182,0.037-0.095,0.022-0.141 and 0.054-0.185,respectively.The percentage weight method shows that the weight ranges of wind cold syndrome,cold yin Syndrome,phlegm heat syndrome,phlegm dampness syndrome and blood stasis syndrome were 0.072-0.102,0.146-0.182,0.057-0.077,0.075-0.111 and 0.115-0.185,respectively.According to the three methods,the weights of wind cold syndrome,cold yin Syndrome,phlegm heat syndrome,phlegm dampness syndrome and blood stasis syndrome were 0.050-0.121,0.117-0.174,0.040-0.117,0.056-0.130 and 0.092-0.188,respectively.Conclusion This study determined the weight of each item of AECOPD-STES,providing a basis for the calculation of syndrome score.

Myxomatous mitral valve degeneration(MMVD)is one of the important pathogenic factors of primary mitral regurgitation.The pathological manifestations of MMVD include thickening,redundancy,and prolapse of the valve leaflets,which lead to structural and functional abnormalities of the mitral valve,eventually cause mitral regurgitation.The pathogenesis of MMVD involves abnormalities in three main cell types:valvular interstitial cells,endothelial cells,and monocyte-macrophages.Therefore,a deep understanding of the regulatory mechanisms of these cell types in MMVD is crucial for the diagnosis and treatment of MMVD.This article provides a comprehensive review of the normal tissue structure characteristics of the mitral valve,the morphological features of MMVD,and the research progress on the regulatory roles of the aforementioned cell types in MMVD,aiming to provide a scientific basis for early intervention and precise treatment of MMVD.

POEMS syndrome is a rare condition associated with plasma cell disorders， and it often involves multiple systems and has diverse clinical manifestations. This article reports two cases of POEMS syndrome with hepatosplenomegaly as the initial manifestation. During the course of the disease， the patients presented with lower limb weakness， hepatosplenomegaly， lymph node enlargement， ascites， hypothyroidism， positive M protein， and skin hyperpigmentation， and ¹⁸F-FDG PET-CT imaging revealed bone lesions mainly characterized by osteolytic changes and plasma cell tumors. There was an increase in the serum level of vascular endothelial growth factor. The patients were finally diagnosed with POEMS syndrome， and the symptoms were relieved after immunomodulatory treatment.

BACKGROUND: Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration. METHODS: Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism. RESULTS: ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression. CONCLUSIONS High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans ; Lung Neoplasms/physiopathology* ; Adenosine Deaminase/genetics* ; Matrix Metalloproteinase 9/genetics* ; Cell Proliferation ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Cell Movement ; Animals ; Mice ; RNA-Binding Proteins/genetics* ; Female ; Male ; Cell Line, Tumor ; Proto-Oncogene Proteins c-fos/genetics* ; Middle Aged ; MAP Kinase Signaling System ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Extracellular Signal-Regulated MAP Kinases/genetics*

BACKGROUND: The choice of unicompartmental knee arthroplasty (UKA) vs . total knee arthroplasty (TKA) in the surgical treatment of knee osteoarthritis (KOA) remains controversial. This study aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the clinical results of UKA and TKA for treating unicompartmental KOA. METHODS: PubMed, Embase, and the Cochrane Library were systematically searched for articles published up to January 2, 2023. The literature was rigorously screened to include only RCTs comparing UKA and TKA for unicompartmental KOA. A systematic review and meta-analysis were performed to calculate the mean difference (MD), relative risk (RR), and 95% confidence interval (CI) according to the Cochrane standards. RESULTS: Thirteen publications involving 683 UKAs and 683 TKAs were analyzed. Except for one study with a follow-up period of 15 years, all outcome measures reported were within 5 years of follow-up. Meta-analysis showed better knee recovery (MD: 1.23; 95% CI: 1.01-1.45; P  <0.001), greater knee function (MD: 1.78; 95% CI: 0.34-3.22; P  = 0.020), less pain (MD: 0.75; 95% CI: 0.43-1.06; P  <0.001), and better health status (MD: 3.75; 95% CI: 0.81-6.69; P  = 0.010) after UKA than TKA. However, considering the minimal clinically important difference values for these variables, the findings were not clinically relevant. Moreover, UKA patients had fewer complications (RR: 0.59; 95% CI: 0.45-0.78; P  <0.001) and shorter hospital stays (MD: -0.89; 95% CI: -1.57 to -0.22; P  = 0.009) than did TKA patients. There were no statistically significant differences in terms of postoperative range of movement, revision, failure, operation time, and patient satisfaction. CONCLUSIONS In terms of clinical efficacy, there was no obvious advantage of UKA over TKA in the surgical treatment of knee OA when considering the minimal clinically important difference. The main advantage of UKA over TKA is that it leads to fewer complications and a shorter length of hospital stay. It is ideal to perform prospective studies with longer follow-up periods to fully evaluate the long-term efficacy and safety of the two procedures in the future.
Humans ; Arthroplasty, Replacement, Knee/methods* ; Osteoarthritis, Knee/surgery* ; Randomized Controlled Trials as Topic ; Treatment Outcome

Objective:To compare the effects of standard cognitive behavioral therapy for insomnia (CBT-I) and enhanced cognitive behavioral therapy for insomnia(CBT-I Plus) in patients with chronic insomnia disorder comorbid anxiety or depressive symptoms.Methods:This prospective study included 148 patients with chronic insomnia disorder and anxiety/depression symptoms who were treated at the Sleep Disorder clinic of Shanghai Mental Health Center between July 2020 and August 2023. Participants (56 males, 92 females; aged 18-65 years, mean age 35.08±10.30 years) were randomly assigned in a 1∶2 ratio to the CBT-I group ( n=54) or CBT-I Plus group ( n=94). The CBT-I Plus group received additional treatments targeting anxiety and depressive symptoms. Treatment lasted 8 weeks, with assessment conducted at baseline, weeks 2, 4, and 8. Depression severity was measured using the 17-item Hamilton Depression Rating Scale (HAMD 17), anxiety severity with the Hamilton Anxiety Scale (HAMA), and sleep quality with the Pittsburgh Sleep Quality Index (PSQI). Paired sample t-tests were used to evaluate within-group changes, repeated-measures ANOVA compared treatment effects between groups, and ANCOVA was employed to adjust for confounding variables. Results:Significant reductions in PSQI, HAMD 17, and HAMA scores were observed in both groups after treatment: CBT-I group: PSQI ((14.15±2.54) vs. (7.50±3.35), t=13.25), HAMD 17 ((14.70±4.09) vs. (7.40±4.61), t=9.33), and HAMA ((14.94±4.11) vs. (5.56±3.67), t=12.38) (all P<0.001).CBT-I Plus group: PSQI ((14.87±3.01) vs. (7.19±3.86), t=18.75), HAMD 17 ((16.84±3.91) vs. (6.84±4.79), t=17.42), and HAMA ((15.57±3.93) vs. (6.10±4.57), t=18.39) (all P<0.001). After adjusting for HAMD 17 scores and medication use, no statistically significant between-group differences were observed in changes in PSQI, HAMD 17, and HAMA scores ( P>0.05). A significant time-by-group interaction was found for the PSQI daytime dysfunction subscale ( F=4.87, P<0.01). Conclusion:Both CBT-I and CBT-I Plus improve sleep and emotional symptoms in patients with chronic insomnia disorder and comorbid anxiety/depression symptoms. However, CBT-I Plus has no significant advantages over standard CBT-I. Further studies are needed to refine the timing and content of interventions.

Objective:To compare the safety, number of lymph nodes removed, rate of lymph node metastasis, and prognosis between proximal gastrectomy (PG) and total gastrectomy (TG) in patients with Siewert types II and III adenocarcinoma of the esophagogastric junction.Methods:In this retrospective cohort study, clinical data of patients diagnosed with adenocarcinoma of the esophagogastric junction at Changzhi People's Hospital, affiliated with Changzhi Medical College, between December 2019 and November 2022, were collected. Patients who had received neoadjuvant therapy, had multiple malignant lesions in the stomach, had concomitant malignancies in other organs, had incomplete clinical data, or had been lost to follow-up were excluded. The study cohort comprised 308 patients, 99 in the PG group and 209 in the TG group. To reduce confounding bias, propensity score matching was performed, matching patients for age, sex, body mass index, tumor diameter, and pathological stage in a 1:1 ratio, resulting in 73 patients in each group. The primary outcomes assessed were operative details, number of lymph nodes dissected, rate of lymph node metastasis, postoperative complications, duration of hospital stay, and follow-up and survival outcomes.Results:The PG group had a significantly shorter median operative time than did the TG group (250 vs. 280 minutes, Z = -4.970, P<0.001), with fewer cases of intraoperative blood loss >100 mL (30.1%[22/73] vs. 46.6%[34/73], χ2=4.171, P=0.041), and a smaller number of lymph nodes removed (median 33 vs. 46, Z =-4.774, P<0.001); all of these differences are statistically significant (all P<0.05). Differences between the two groups in postoperative hospital stay and postoperative complications were not statistically significant (both P>0.05). Furthermore, no statistically significant differences were found between the PG and TG groups in the number of lymph nodes dissected or the lymph node metastasis rates at stations No. 1, No. 2, No. 3, No. 4sa, No. 4sb, and No. 7 (all P> 0.05). Among the 209 patients in the TG group, analysis of risk factors for metastasis to distal perigastric lymph nodes (No.4d, No.5, and No.6) showed that patients with tumor diameters ≤4 cm and T1–T3 stage disease had significantly lower rates of metastasis to these lymph nodes than did patients with tumor diameters >4 cm and/or T4 stage disease (0/78 vs. 12/131 [9.2%]); these differences are statistically significant ( P=0.014). The median duration of follow-up for the entire cohort was 26 months. The 3-year overall survival rates for the PG and TG groups were 62.5% and 63.3%, respectively; this difference is not statistically significant (χ 2=0.330, P = 0.565). Multivariate analysis showed that older age ( P = 0.035) and advanced pathological stage ( P = 0.018) were significant independent risk factors that affected overall survival in patients with Siewert type II and III adenocarcinoma of the esophagogastric junction. Conclusions:PG is safe and feasible for patients with Siewert types II and III adenocarcinoma of the esophagogastric junction. The number of lymph nodes dissected and metastasis status were similar in the TG and PG groups.

Objective To construct a nursing registry platform for percutaneous coronary intervention(PCI)to provide data support for subsequent real-world research on PCI nursing.Methods From April to December 2023,we established a variable list and data dictionary based on literature review and expert discussion,and constructed a web-based PCI nursing registry platform based on registry-related standards.Results A total of 191 variables were screened in this study,and a corresponding data dictionary was developed for each variable according to the variable name,variable code,variable definition,variable type,variable value range,data source and data collection node.Three levels of account privileges has been set up in the platform,which can realize different data management privileges,and the data can be saved only after filling in and reviewing at each level.The platform is also equipped with automatic data checking function,which reduces data filling errors and improves data quality.Conclusion The constructed PCI nursing registration platform has strong scientific and professional characteristics,and can provide data support for subsequent research,and the content and functions of the platform can be further optimized in the future.