Latest ArticlesDiabetic cardiomyopathy is one of the chronic irreversible and serious cardiovascular complications in diabetic patients. Recent studies have shown that the mitochondrial dysfunction caused by the disturbance of mitochondrial dynamic balance is closely related to the occurrence of diabetic cardiomyopathy. Dynamin related protein 1 (Drp1) is an important regulator of mitochondrial fission. Studies have shown that increased activity of Drp1 in diabetes cardiomyocytes can lead to increased mitochondrial fission and decreased mitochondrial fusion which leads to mitochondrial dysfunction. Drp1 can lead to the occurrence and development of diabetic cardiomyopathy by inducing oxidative stress, energy metabolism disorders, apoptosis,insulin resistance, and lipotoxicity in cardiomyocytes. In addition, inhibition of Drp1 activity may improve cardiac function in diabetic cardiomyopathy. Therefore, the mechanism of Drp1 in diabetic cardiomyopathy have been reviewed in present paper in order to provide new ideas for the prevention and treatment of diabetic cardiomyopathy and drug development.
Objective To explore the feasibility of rapid saline infusion ultrasound imaging for the assessment of the central venous catheter tip location. Methods A total of 83 critically ill adult patients with indications for central venous catheterization who were admitted to Peking University People's Hospital from July 2020 to July 2021 were selected. Cardiac ultrasonography was used to observe the turbulent flow imaging formed after rapid injection of normal saline into the central venous catheter to quickly determine the exact position of the catheter tip, and compared with the results of bedside chest X-ray to evaluate the method of rapid injection of normal saline effectiveness. Results The results of judging the position of the tip of the central venous catheter by the rapid perfusion ultrasound imaging of normal saline and bedside chest X-ray were basically consistent (Kappa=0.917, P<0.05). The rapid saline infusion ultrasound imaging had a sensitivity of 100.0%(95%CI 94.0%-100%)and specificity of 85.7%(95%CI 42.0%-99.2%). It took 77.5 (69.5, 85.5) minutes to determine the catheter position by chest X-ray, which was significantly longer than that of normal saline perfusion ultrasound imaging [6.4 (5.8, 6.9) minutes], and the difference was statistically significant (P<0.05). Conclusion The rapid saline infusion ultrasound imaging can effectively determine the tip position of the central venous catheter and the diagnosis time is shorter than that of the bedside chest X-ray examination.
Artificial intelligence has made breakthroughs in medicine in the past decade. Compared with the traditional statistical model, the advantage of artificial intelligence is that it can establish algorithm and prediction model through machine learning to efficiently and effectively identify the patterns in large data sets, and combine a variety of factors to create more accurate prediction model. Therefore, artificial intelligence is particularly suitable for huge and complex or high-dimensional clinical data analysis and predictive modeling tasks. There are many kinds of data formats in the clinical practice of hepatology. Many studies have applied artificial intelligence in the diagnosis and classification of liver diseases, assisting treatment, predicting efficacy and prognosis, and evaluation of liver imaging and pathology. Based on the study outcomes in related fields at home and aboard, this paper summarizes the research progress and application of artificial intelligence in the field of diagnosis and treatment of chronic liver diseases.
Objective To prepare fibrin-targeted, integration of diagnosis and treatment and multi-functional gelatin nanoparticles, explore their potential of dual-mode imaging and the mechanism and effect of photothermal synergistic drug thrombolytic therapy in vitro, and observe the active-targeting ability of thrombus in vivo. Methods Loaded with alteplase (rt-PA)and Fe3O4 mediated by targeting fibrin polypeptide (Cys-Arg-Glu-Lys-Ala, CREKA), the magnetic gelatin nanoparticles (CREKA-Fe-rt-PA-Gel) were prepared by two-step desolvation and carbodiimide method. The morphology of CREKA-Fe-rt-PA-Gel was observed, and its physical and chemical properties and in vitro safety were detected. Its photoacoustic (PA) and magnetic resonance(MR) imaging features were also verified in vitro. The photothermal performance was monitored, the fibrin and hemoglobin indexes were used to evaluate the thrombolytic effect of photothermal therapy and the ability to damage fibrin network. Carotid artery thrombosis model was constructed with rats and HE staining section was performed to observe the targeting thrombus ability in vivo of the nanoparticles. Results CREKA-Fe-rt-PA-Gel were with uniform particle size, diameter of (254.79±6.83) nm, polydispersity coefficient of 0.09±0.05, surface potential of (5.48±4.60) mV. The CREKA peptide was successfully connected with the target connection rate of 98.66%, the encapsulation efficiency of rt-PA was 23.03%±0.05%, and of Fe3O4 was 92.78%±0.57%, the magnetization curve showed that it has good paramagnetism. The cytotoxicity and hemolysis test in vitro confirmed that CREKA-Fe-rt-PA-Gel had appropriate biological compatibility. At the same time, CREKA-Fe-rt-PA-Gel showed excellent imaging ability of PA and MR imaging in vitro. After laser irradiation, the nano solution heated up rapidly in a concentration-dependent manner,hemoglobin and fibrin in solution increased significantly after incubation with thrombus by near infrared irradiation (P<0.01), and nanoparticles released drugs combined with photothermal therapy could damage the fibrin network. HE staining of carotid artery thrombosis in rats showed good thrombus targeting ability of the nanoparticles in vivo. Conclusion The constructed CREKA-Fe-rt-PA-Gel have potential in dual-mode (PA/MR) imaging, good photothermal properties, outstanding targeting ability for thrombus(fibrin), and excellent thrombolytic ability when combined with photothermal, which is expected to be used in early diagnosis and multi-form treatment in clinical thrombotic diseases.
Small cell lung cancer (SCLC) is an aggressive malignancy with a 5-year survival rate of 7.2%, which is characterized by exceptionally high proliferation rate, early metastasis, and poor prognosis. In the face of DNA damage and replicative stress, the DNA damage response (DDR) elicits activation of cell cycle checkpoints to promote repair by pausing the cell cycle or, in cases of unrepairable DNA damage, stimulate programmed cell death. SCLC carries a high mutation burden and genomic instability, and almost all SCLC tumors have functional inactivation of both TP53 and RB1, which leads to the form of a dysfunctional G1/S checkpoint and results in an increased reliance on subsequent cell cycle checkpoints (S, G2/M) to ensure genome stability and correct chromosomal segregation. Therefore, under the use of radio-chemotherapy for DNA damaging, promoting the cell cycle progress by inhibiting the cycle checkpoints and increasing DNA damage by inhibiting DNA damage repair can be new strategies for targeted therapies in SCLC. In the present article, we review the advances of targeting DDR and it's pathway inhibitors in SCLC, and provide some thoughts for the targeted treatment strategies of SCLC.
Objective To study the effect of Fritillaria cirrhosae bulbus on ovalbumin (OVA)-sensitized asthmatic mice and its mechanism. Methods We set up the study including a blank control group, OVA model group (intraperitoneal injection of 0.2 mg OVA to induce sensitization), dexamethasone group (after successful modeling, intraperitoneal injection of 0.5 mg/kg dexamethasone), and Fritillaria cirrhosae bulbus low, medium and high dose groups (after successful modeling, gavage 7.0 mg/kg,14.0 mg/kg, 21.0 mg/kg Fritillaria cirrhosae bulbus), once a day for 4 weeks, with 10 mice in each group (total=60 BALB/c mice).After drug administration, we measured the amount of phenol red excretion in the airway and collected the bronchoalveolar lavage fluid (BALF) to determine the content of brain-derived neurotrophic factor (BDNF) and the number of inflammatory cells. We also took the blood samples through eyeballs followed by quantifying the concentration of serum immunoglobulin E (IgE), interleukin-4(IL-4), IL-13, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) using ELISA. We further collected the lung tissues and detected the mRNA and protein expressions of Janus kinase 3 (JAK3), signal transducer and activator of transcription 6 (STAT6),and IL-4 by RT-qPCR and Western blotting. Results Compared with the blank control group, the level of phenol red in the airway of the OVA model group reduced significantly, the content of BDNF as well as the number of inflammatory cells in BALF increased significantly, the contents of IgE, IL-4, IL-13, and TNF-α in serum were significantly elevated, the concentration of IFN-γ and IFN-γ/IL-4 ratio decreased significantly, the relative expression levels of JAK3, STAT6, IL-4 mRNA and p-JAK3/JAK3, p-STAT6/STAT6, and IL-4 protein in lung tissue increased significantly (P<0.05). Compared with the OVA model group, the above indexes were all significantly improved in each dose of the Fritillaria cirrhosae bulbus groups, and the high Fritillaria cirrhosae bulbus dose group had the best index (P<0.05). Conclusion The mechanism of Fritillaria cirrhosae bulbus regulating airway and lung inflammation in asthmatic mice may be related to inhibiting the activation of JAK3/STAT6 signal pathway.
Vascular complications of type 2 diabetes mellitus (T2DM) include macrovascular complications and microvascular complications, of which the increased incidence is often accompanied with a high incidence of obesity. Obesity is an independent risk factor for T2DM. In obese patients, body fat distribution rather than total body fat is associated with metabolic and cardiovascular risk. Body mass index (BMI) and waist circumference (WC) cannot accurately reflect body fat distribution in obese patients, so visceral fat has received more and more attention and may be as a related risk factor for vascular complications in T2DM.The research progress on the relationship between visceral fat and vascular complications of T2DM and its action mechanism have been reviewed in present paper, in order to provide a reference for in-depth research and clinical examination of visceral fat.
Objective To explore the mutation status of KRAS, NRAS, PIK3CA, and BRAF, and the relations with clinicopathological features and hormone expression levels in ovarian low-grade serous tumors. Methods Tissue specimens (23 cases of common-type serous borderline tumor, 27 cases of micropapillary serous borderline tumor and 14 cases of low-grade serous carcinoma) were collected from the First People's Hospital of Yunnan Province during January 2017 to April 2021, and then retrospectively analyzed. The mutation status of human KRAS, NRAS, PIK3CA and BRAF genes were detected by expression status in tumor tissues was detected by immunohistochemistry, the relationship was analyzed between gene mutation status and clinicopathological features and hormone expression levels. Results A total of 36 mutations were detected in 64 tumor tissues,including 21 KRAS mutation, 12 BRAF mutation, 2 PIK3CA mutation and 1 NRAS mutation. KRAS and BRAF mutations were common in younger women ≤35 years old. In the KRAS mutant subtype, G12S and G12D mutations are common in micropapillary serous borderline tumor (P<0.05); G12C, G12R*, G12V, G12A, and G13C* mutations are common in common-type serous borderline tumor (P<0.05); G13D mutation was only detected in low-grade serous carcinoma. Patients with BRAF mutations were all seen in the early stages of the disease. Immunohistochemistry showed the positive expression rates of both estrogen receptor and progesterone receptor were 76.6% (49/64). The positive expression rate of common-type serous borderline tumor was similar to that of micropapillary serous borderline tumor, and both of them were significantly higher than that in lower-grade serous carcinoma(P<0.05). KRAS G13D mutation was significantly associated with low progesterone expression (P<0.05). Conclusion Gene mutations were mutual exclusion. KRAS mutation was an oncogenic driving factor in serous tumors, and different mutant subtypes were associated with histological type and progesterone receptor expression status. As the disease progresses, BRAF mutation rate gradually decreased and associated with a variety of clinicopathological features and good prognosis and might have a protective effect against disease progression. The mutation rates of NRAS and PIK3CA were lower.
The incidence and mortality of malignant tumors are gradually increasing all the world, and the existing diagnosis and treatment methods still can not effectively block the occurrence and development of tumors. Some studies have found that cancer stem cells (CSCs) are the cells of tumor origin, and closely related to the occurrence, development and metastasis of tumors.Early detection and intervention with effective treatment of CSCs are expected to prevent the occurrence and development of tumors. Many studies have shown that the activation of Wnt/β-catenin signaling pathway is an important link in the initiation of CSCs and the formation of tumors. Therefore, by regulating the key upstream and downstream factors of the Wnt/β-catenin pathway in CSCs, thereby regulating the activity of the Wnt/β-catenin signaling pathway, controlling tumor growth and metastasis,can provide new targets and directions for the treatment and prevention of malignant tumors. The key role of Wnt/β-catenin signal pathway in CSCs, and the related mechanisms of the important factors of the pathway in regulating the tumor growth, development and metastasis of CSCs in different organs are reviewed in present paper.
Objective To report a case of gastric ulcer associated with cytomegalovirus (CMV) infection in immunocompetent for improving the clinical recognition of the disease. Methods A 69-year-old patient with gastric ulcer caused by CMV infection was admitted to the 900th Hospital of the Joint Logistics Team on August 10, 2020. Biopsies were performed at the gastric ulcer and biopsy gastric mucosa samples were measured by hematoxylin-eosin (HE) staining and immunohistochemistry.The microscopic characteristics of the mucosal tissues, diagnosis and treatment experience of this case were analyzed and summarized. A literature review about CMV infection in gastric in inmmunocompetent patients was performed using PubMed search from database inception to July 2021. Results A total of 20 literatures were retrieved, involving 57 patients. A total of 58 patients were included in this article, including 39 males (67.2%) and 19 females (32.8%), with a ratio of men to women of 2.05:1. The average onset age of male was (52.4±16.0) years old, while (72.3±17.7) years old in female. The overwhelming majority of those patients were complicated with hypertension or type 2 diabetes mellitus. The most common symptoms were upper abdominal pain and gastrointestinal bleeding. The antrum of stomach was the most frequently affected site in gastric CMV disease, isolated gastric ulcer and multiple mucosal erosion were the main endoscopic appearance. CMV inclusion bodies were found either at the ulcer base or at the ulcer edges. There were 51.1% (24/47) of the patients treated with ganciclovir. However, 48.9% (23/47) of the patients were cured by symptomatic treatment. Conclusions On no consideration can clinically ignore CMV gastritis in adults without apparent immunosuppression when the symptoms as hematemesis, melena, and abdominal pain occur and antral gastric ulcer or multiple mucosal inflammation is seen endoscopically. Biopsies for CMV related tests, especially for pathological examination or histopathologic diagnosis are recommended. Antiviral therapy in people with clinical risk factors is essential for management of gastric CMV disease.