Alzheimer's disease(AD)is a progressive neurodegenerative disease characterized by cognition impairment and behavioral abnormalities.While the mechanisms involved in AD remain unclear,various hypotheses have been proposed regarding pathogenesis of AD,among which the oxidative stress hypothesis has attracted more and more attention.In the present article,the relationship between oxidative stress and AD is reviewed,including sources of neuronal oxygen radical generation,the link of oxidative stress to pathogenesis of AD,preclinical and clinical studies of AD,therapeutic effects of antioxidants and phosphodiesterase inhibitors on AD.

Objective To imitate the development process of new drugs with rutin as the model and to do multidiscipli-nary experiments of preparation and pharmacodynamics of rutin tablets .Methods Thin-layer chromatography was used to i-dentify rutin in Pagodatree flower bud .High-performance liquid chromatography was used for quantitative determination of ru-tin in Pagodatree flower bud and rutin products .The vasodilatation effect of rutin was investigated .The preparation of rutin tablets was completed .Results and Conclusion We completed the identification of Pagodatree flower bud ,extraction and puri-fication of rutin from Pagodatree flower bud ,the assay of rutin ,the pharmaco-dynamics study and the formulation of rutin tab-lets .The experiments helped the postgraduates to be familiar with the research process of new drugs and to improve their ex-perimental operation skills .

Objective To investigate the optimal method for synthesizing thiolated doxorubicin .Methods Thiolated doxorubi-cin was synthesized through two different methods .Doxorubicin was reacted with 2-iminothiolane (2-IT) and S-acetylthioglycolic acid N-hydroxysuccinimide ester (SATA),respectively.The synthesized thiolated doxorubicin was further characterized by HPLC and MS -ESI techniques .Several factors including molar ratios as well as reaction time were evaluated .Results The results showed that thiolat-ed doxorubicin could be synthesized via both of the two methods successfully .Thiolated doxorubicin could be stable when doxorubicin was reacted with SATA .But the crude thiolated doxorubicin could be cyclized easily when doxorubicin was reacted with 2-IT.Conclu-sion Thiolated doxorubicin prepared with SATA is more feasible than that with 2-IT.

Objective To analysis the clinicopathological features of skip N2 metastasis in NSCLC in our clinical center,therefore guide for clinical decision making for NSCLC patients.Methods A total of 120 NSCLC patients with N2 metastasis treated by surgery were enrolled from January 2017 to May 2018,of which 55 were males and 65 were females.The mean age of them were (58.36 ± 11.34) years old.36 patients had skip N2 metastasis,accounting for 30％ of patients with N2 metastasis.48 patients had a history of smoking or a definitive history of second-hand smoke exposure,compared with other 72 patients.Collected pre-and post-operation clinical data of those patients,and carried out relevant statistical analysis.Results Among the NSCLC with skip N2 metastasis,it occulted more frequently in right lower lobe and peripheral lung cancer.The main pathological type was adenocarcinoma with acinar subtype.The most cases of skip N2 metastasis were characterized by single N2 station metastasis.Age of patients showed a significant difference between the two groups(P =0.049).Gender,smoking history,T staging of lung cancer,pathological type and involvement of pulmonary membrane showed no statistic difference between the two groups(P ＞ 0.05).Conclusion Patient with skip N2 metastasis seemed to be elder,and the lesions of those patients were more likely to be lung adenocarcinoma in the right lower lobe and peripheral lung cancer,often involved single N2 station.The lung cancer in right upper lobe often skipped to level R2 + R4,which in right middle lobe often skipped to levels R2 + R4 and 7,in right and left lower lobes skipped to level 7,in the left upper lobe often skipped to level 5.

Objective:To analyze clinical features of aortoesphageal fistula (AEF) patients with massive upper gastrointestinal hemorrhage.Methods:Five AEF patients with massive upper gastrointestinal hemorrhage admitted in Peking Union Medical College Hospital from 2016 January 1st to 2019 December 31st. The clinical data, endoscopic findings, radiological manifestations, treatment and clinical outcomes were retrospectively analyzed.Results:Among 5 patients, 4 were males, 1 was female with an average age of (58±8) years old. The underlying conditions were atherosclerosis ( n=4), hypertension ( n=3), hyperlipidemia ( n=1); 2 cases had aortic aneurysm stent implantation and 1 case of rheumatic heart disease had valve replacement. All 5 patients were complicated with hematemesis and hypovolemic shock, and 4 cases had sentinel hemorrhage. Contrast-enhanced CT or CT angiography of the aorta showed thicken esophageal wall, local esophageal discontinuity, aortic aneurysm, gas around the aortic stent and contrast agent spilling over. The gastroscopy showed esophageal depression lesions, deep ulcers, mucosal erosion with bleeding. Conservative therapy and endoscopic hemostasis failed, 2 patients died without surgical intervention; 3 patients underwent emergency surgeries, 2 survived and 1 died perioperatively. Conclusions:Aortoesophageal fistula is in lack of specific clinical manifestations but is highly in mortality. Therefore CT and gastrocopic examination should be performed for suspected patients, early diagnosis and surgical treatment are the key to save patients′ lives.

Small cell lung cancer carries the worst prognosis among lung cancer. The current guidelines only recommend surgical treatment for patients in the Ⅰ-ⅡA stage, but surgical treatment is often in a neglected position in clinical practice. More and more recent studies have focused on this aspect. This article reviews the recent research literatures and reviews the progress of surgery in the multidisciplinary treatment of small cell lung cancer.

Objective    To investigate the clinical characteristics and treatment of primary mediastinal yolk sac tumor (PMYST). Methods    We collected the clinical data of PMYST patients who were admitted to the Department of Thoracic Surgery of Peking Union Medical College Hospital from September 2000 to September 2020. The clinical and pathological characteristics, treatment and prognosis of PMYST patients were retrospectively analyzed. Results     Finally 18 patients were enrolled, including 17 males and 1 female with a median age of 22.0 (16.6, 26.2) years. Patients had increased level of alpha fetoprotein (AFP). The pathological type can be single yolk sac tumor or combined with other mediastinal germ cell tumors. Chemotherapy and radical surgery were the main treatment methods. Extensive resection was feasible for patients with tumor invasion of other organs. Seven patients developed lung or pleural metastasis after operation, and 3 of them had extrapleural metastasis. One patient recurred within 1 year after surgery. All patients were followed up by telephone or outpatient department. At the last follow-up, 5 patients survived, 9 died, and 4 were lost to follow up, with a median survival of 16.8 months. The median disease-free survival was 14.9 months. The survival rates at 1, 3 and 5 years were 73.3%, 28.6% and 11.8%, respectively. Conclusion    PMYST often occurs in young-middle aged male patients. Preoperative puncture can provide an effective diagnostic basis. R0 resection, AFP returning to normal after treatment and no metastasis may be potential indicators of good prognosis. The overall prognosis of PMYST is poor, and some patients can achieve long-term survival after treatment.

Melanoma is the most aggressive cutaneous tumor. Neuropilin and tolloid-like 2 (NETO2) is closely related to tumorigenesis. However, the functional significance of NETO2 in melanoma progression remains unclear. Herein, we found that NETO2 expression was augmented in melanoma clinical tissues and associated with poor prognosis in melanoma patients. Disrupting NETO2 expression markedly inhibited melanoma proliferation, malignant growth, migration, and invasion by downregulating the levels of calcium ions (Ca²⁺) and the expression of key genes involved in the calcium signaling pathway. By contrast, NETO2 overexpression had the opposite effects. Importantly, pharmacological inhibition of CaMKII/CREB activity with the CaMKII inhibitor KN93 suppressed NETO2-induced proliferation and melanoma metastasis. Overall, this study uncovered the crucial role of NETO2-mediated regulation in melanoma progression, indicating that targeting NETO2 may effectively improve melanoma treatment.
Humans ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism* ; Cell Line, Tumor ; Cell Proliferation ; Melanoma/genetics* ; Membrane Proteins/genetics* ; Phosphorylation ; Signal Transduction

The 2020 Nobel Prize in Chemistry recognized CRISPR-Cas9, a super-selective and precise gene editing tool. CRISPR-Cas9 has an obvious advantage in editing multiple genes in the same cell, and presents great potential in disease treatment and animal model construction. In recent years, CRISPR-Cas9 has been used to establish a series of rat models of drug metabolism and pharmacokinetics (DMPK), such as

Thymic neuroendocrine tumors (TNETs) are a series of rare diseases with aggressive biology and poor prognosis. Clinical manifestations of TNETs are atypical, and ectopic secretion of adrenocorticotropic hormone can be found in some cases, resulting in associated endocrine symptoms. Due to the low morbidity and strong heterogeneity, it’s difficult to diagnose, treat and obtain new treatment regimen. Early complete surgical resection is an effective treatment. For advanced cancer, clinical trials of new drugs are expected to improve the survival of patients.