Objective To explore the correlation of MET status in patients with advanced prostatic acinar adenocarcinoma with the clinical pathological parameters and prognosis. Methods The specimen from 135 patients with advanced prostatic acinar adenocarcinoma was included. The expression of c-MET protein was detected via immunohistochemistry, and MET gene amplification was assessed by fluorescence in situ hybridization. The relationships of c-MET expression and gene amplification with clinicopathological features and prognosis were analyzed. Results The positive expression rate of c-MET was 52.60% (71/135). Compared with the c-MET expression in adjacent tissues, that in tumor tissues showed lower heterogeneous expression. Among the cases, 1.71% (2/117) exhibited MET gene polyploidy, but no gene amplification was detected. Positive c-MET expression was significantly correlated with high Gleason scores and grade groups (P=0.0073). However, no significant relationship was found between c-MET expression and progression-free survival or post-treatment t-PSA levels. Conclusion c-MET protein is expressed at a relatively low level in advanced prostatic acinar adenocarcinoma, suggesting that c-MET may not be a viable target for ADC drug development in prostatic acinar adenocarcinoma.

Objective To explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

Syncytial giant cells (SGCs) are epithelial giant cells with multiple uniform and similar nuclei. Clear cell renal cell carcinoma (ccRCC) with SGCs is a rare microscopic morphology. A 70-year-old man was admitted to hospital with multiple nodules in both lungs found by chest CT examination 2 weeks before. A left renal carcinoma with lung metastasis was considered by PET-CT. Cytoreductive nephrectomy was performed, and postoperative pathological diagnosis confirmed ccRCC with SGCs of the left renal. Combined immunotherapy and targeted therapies were administered. There was no disease progression during follow-up period of 28 months.

Vascular cognitive impairment is a group of disorders characterized by cognitive dysfunction caused by vascular factors. Disruption of the blood-brain barrier is an early pathophysiological mechanism of vascular cognitive impairment. Dynamic contrast-enhanced magnetic resonance imaging and arterial spin labeling-based blood-brain barrier imaging techniques can quantitatively assess the integrity of the blood-brain barrier. In recent years, these techniques have gradually been applied to detect the extent of blood-brain barrier dysfunction. This article provides a comprehensive review of the basic principles of relevant magnetic resonance techniques and the progress made in their application to the assessment of the blood-brain barrier in vascular cognitive impairment.

Myopia is becoming more and more common all over the world, and the incidence of myopia is gradually increasing. Many treatments have been used to prevent and control myopia, including optics, drugs, environment or behavior, but the results are different and lack standardization. At present, many experiments have proved that peripheral defocus technology has a certain effect on myopia control. Based on this technology, three kinds of framed eyeglass lenses with peripheral defocus design, namely defocus incorporated multiple segments(DIMS), highly aspherical lenslets(HAL)and cylindrical annular reactive elements(CARE), are commonly used in medical and optometry institutions in China. These lenses provide not only clear vision in the central area, but also a certain amount of myopic defocus in the periphery to control the progression of myopia. This paper aims to focus on the design principle and myopia prevention and control effect of the above three peripheral defocus lenses, and evaluate their effectiveness in clinical practice.

Objective To understand the change trend of doctor trustrank among the residents,and to analyze its influencing factors to provide reference for finding the effective strategies to enhance the doctor trustrank.Methods The analytical framework was constructed based on the social determinism.The data from the China Family Panel Studies(CFPS)in 2014,2016,2018 and 2020 were adopted to analyze the change trend of residents'doctor trustrank.The OLS regression model was used to explore the influencing factors,and the Shapley value decomposition model was used to analyze the contribution degree of influencing factors on doctor trustrank.Results The residents'doctor trustrank was gradually decreased in 2014,2016 and 2018(6.817,6.762,6.730),which in 2020 was significantly increased(7.151).The OLS regression model analysis showed that the personal characteristics,social trust,quality of medical services,access to information and subjective socioeconomic status were related to the residents'doctor trustrank.The social trust during 2014-2020 was the main factor affecting the residents'doctor trustrank,followed by the medical service quality,subjective socialeconomic status and information channels.The personal characteristics had the lowest contri-bution degree to doctor trustrank.Conclusion The residents'doctor trustrank is comprehensively affected by the factors such as social trust,medical service quality,subjective socioeconomic status and information chan-nels.It is needed to optimize the comprehensive treatment measures to promote the persistent elevation of doctor trustrank.

Objective:To evaluate the effects of cup-stacking task based on the dyadic coping model in patients with ischemic stroke, in order to provide reference for clinical nurses to effectively rehabilitate these patients and improve their disease coping ability.Methods:This was a quasi-experimental study, a total of 90 patients with upper extremity motor function disorder after ischemic stroke admitted to the Neurology of the First Affiliated Hospital of Zhengzhou University were selected as participants from October 2022 to March 2023. Among them, 45 patients admitted from October 2022 to December 2022 were selected as the control group, 45 patients admitted from January 2023 to March 2023 were selected as the experimental group. Patients in the control group received routine care and patients in the experimental group received cup-stacking task based on the dyadic coping intervention model. The dyadic coping between the two groups and their spouses were compared before intervention and after intervention(3 months after discharge), the upper extremity motor function, activities of daily living, anxiety, rehabilitation self-efficacy between the two groups were compared before the intervention and after intervention.Results:A total of 5 patients were dropped and 43 patients of the control group and 42 patients of the experimental group completed the study at last. In the control group, there were 28 males, 17 females, aged (61.84 ± 7.13) years old; while their spouses were 17 males, 26 females, aged (61.02 ± 6.79) years. In the experimental group, there were 28 males, 14 females, aged (62.36 ± 7.03) years old; while their spouses were 14 males, 28 females, aged (60.95 ± 6.81) years. After the intervention, the scores of the dyadic coping between the experimental group patients and their spouses were (135.05 ± 8.52), (139.24 ± 9.67) points, which were higher than (119.26 ± 12.23), (120.02 ± 12.34) points of the control group, the differences were statistically significant ( t=6.92, 8.00, both P<0.05); the scores of the upper extremity motor function, activities of daily living, rehabilitation self-efficacy of the experimental group patients were (55.48 ± 4.78), (79.55 ± 6.83), (83.64 ± 10.30) points, which were higher than (51.44 ± 6.20), (72.74 ± 8.93), (70.28 ± 13.13) points of the control group, the differences were statistically significant ( t=3.36, 3.94, 5.21, all P<0.05); the score of anxiety was (13.26 ± 2.96) points, which was lower than (18.53 ± 3.35) in the control group, and the difference was statistically significant ( t=-7.69, P<0.05). Conclusions:The cup-stacking task based on the dyadic coping model can effectively improve the dyadic coping level of patients after ischemic stroke and their spouses, improve the patients′ upper extremity motor function and rehabilitation self-efficacy, so as to facilitate disease recovery and improve the quality of life, which is worthy of clinical promotion.

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE^-/-LDLR^-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

Objective:To investigate the clinical characteristics, treatment and prognosis of newly-treated patients with primary central nervous system lymphoma (PCNSL).Methods:Clinical data of 117 newly-treated PCNSL patients who were admitted to the First Hospital of Jilin University, the Fifth Medical Center of Chinese PLA General Hospital, Harbin Medical University Cancer Hospital, and Cancer Hospital of Chinese Academy of Medical Sciences & Peking Union Medical College from August 2009 to February 2018 were retrospectively analyzed. The patients' age, sex, Eastern Cooperative Oncology Group (ECOG) physical status (PS) score, pathological type, involvement of deep brain tissue, number of lesions, cerebrospinal fluid protein concentration, International Extranodal Lymphoma Study Group (IELSG) score, Memorial Sloan Kettering Cancer Center (MSKCC) score, treatment strategy, and response after the first-line therapy were analyzed using univariate and multivariate Cox proportional hazards models to identify the independent influencing factors for progression-free survival (PFS) and overall survival (OS) of PCNSL patients. Kaplan-Meier method was used for survival analysis.Results:In 117 newly-treated PCNSL patients, 59 cases (50.4%) presented with increased intracranial pressure or focal neurological symptoms at diagnosis; there were 65 cases (55.6%) with single lesions and 52 cases (44.4%) with multiple lesions; 1 patient (0.9%) had lymphoma of T-cell origin, and 116 cases (99.1%) had diffuse large B-cell lymphoma (DLBCL). Among 95 evaluable patients, 41 patients (43.2%) achieved complete remission (CR), 20 patients (21.1%) achieved partial remission (PR), 16 patients (16.8%) achieved stable disease (SD), and 18 patients (18.9%) had progressive disease (PD). In 117 patients with median follow-up of 66.0 months (95% CI 57.9-74.1 months), the median PFS and OS were 17.4 months (95% CI 11.5-23.3 months) and 45.6 months (95% CI 20.1-71.1 months), respectively. The 2-, 3- and 5-year PFS rates were 41.2%, 28.6% and 19.3%, and OS rates were 63.7%, 52.4% and 46.3%, respectively. Univariate Cox regression analysis showed that baseline high-risk MSKCC score group was an adverse prognostic factor for PFS ( P = 0.037), and the first-line chemotherapy with ≥4 cycles of high-dose methotrexate (HDMTX), HDMTX in combination with rituximab, ≥4 cycles of rituximab in combination with HDMTX, and achieving CR or ≥PR after the first-line treatment reduced the risk of disease progression and prolonged the PFS time (all P <0.01); age >60 years old, ECOG-PS score of 2-4 points, elevated cerebrospinal fluid protein concentration, high-risk IELSG score, and high-risk MSKCC score were adverse prognostic factors for OS, and ≥4 cycles of HDMTX and achieving CR or ≥PR after the first-line treatment were favorable factors for OS. Multivariate Cox regression analysis verified that rituximab in combination with HDMTX (yes vs. no: HR = 0.349, 95% CI 0.133-0.912, P = 0.032) and achieving ≥PR after the first-line chemotherapy (yes vs. no: HR = 0.028, 95% CI 0.004-0.195, P < 0.001) were independent favorable factors for PFS; age >60 years old (>60 years old vs. ≤60 years old: HR = 10.878, 95% CI 1.807-65.488, P = 0.009) was independent unfavorable factor for OS, while ≥4 cycles of HDMTX treatment (≥4 cycles vs. <4 cycles: HR = 0.225, 95% CI 0.053-0.947, P = 0.042) was independent favorable factor for OS. Conclusions:The older the PCNSL patients at initial treatment, the worse the prognosis. Intensive and continuous treatment for achieving deeper remission may be the key for improving the outcome of PCNSL patients.

Lung cancer is the most common malignancy in the world and the leading cause of cancer death. Human epidermal growth factor receptor 2 (HER2) positive non-small cell lung cancer (NSCLC) refers to the NSCLC caused by mutation, amplification or overexpression of the HER2 gene, resulting in its dysfunction. HER2 is the most active receptor in the HER family and can combine with other members to form dimers, which can activate multiple signaling pathways and regulate cell proliferation, differentiation, migration and apoptosis. In NSCLC, HER2 positivity is usually considered a poor prognostic marker. At present, the diagnosis and treatment of HER2-positive NSCLC are not mature. Immunohistochemistry (IHC), next generation sequencing (NGS) and other technologies are often used to detect the positive status of HER2 mutation, amplification or overexpression. In previous studies, antitumor drugs did not show ideal therapeutic effects in HER2-positive NSCLC. However, in recent years, related researches have shown that antibody-drug conjugates (ADCs) and new tyrosine kinase inhibitors (TKIs) in targeted therapy show good antitumor activity against HER2 positive NSCLC. This article summarized the progress in diagnosis and treatment of HER2-positive NSCLC, so as to provide reference for subsequent researches.
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Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Receptor, ErbB-2/genetics* ; Mutation ; Antineoplastic Agents/pharmacology* ; Signal Transduction ; Protein Kinase Inhibitors/therapeutic use*