Small molecules targeting protein-protein interactions for cancer therapy

Protein-protein interactions (PPIs) are fundamental to many biological processes that play an important role in the occurrence and development of a variety of diseases. Targeting the interaction between tumour-related proteins with emerging small molecule drugs has become an attractive approach for treatment of human diseases, especially tumours. Encouragingly, selective PPI-based therapeutic agents have been rapidly advancing over the past decade, providing promising perspectives for novel therapies for patients with cancer. In this review we comprehensively clarify the discovery and development of small molecule modulators of PPIs from multiple aspects, focusing on PPIs in disease, drug design and discovery strategies, structure-activity relationships, inherent dilemmas, and future directions.

Analysis of neoplasm invasion type in ovary of the orthotopic epithelial ovarian carcinoma model in nude mice and human epithelial ovarian cancer / 中国医师杂志

Objective:The aim of this study was to study the characteristics of neoplasm invasion type in ovary of two orthotopic models established with human epithelial ovarian cancer solid tumor tissue slices and human ovarian carcinoma cell line OVCAR-3 in nude mice and human epithelial ovarian cancer.Methods:Tumor tissues and cell line OVCAR-3 of human epithelial ovarian cancer were grown in subcutaneous tissue and the subcutaneous tumor source was fetched and inoculated in ovarian capsule of nude mice to establish the orthotopic implantation model. The neoplasm invasion type in the two kinds of models were observed. The neoplasm invasion types were also analyzed by pathological examination in 54 cases of International Federation of Gynecology and Obstetrics (FIGO) stageⅠ-Ⅱepithelial ovarian cancer.Results:Three neoplasm invasion types were found as follows: type of pseudocapsule, type of pseudocapsule invasion, type of pseudocapsule penetration. Pseudocapsule rate in the solid tumor slices group (18.2%) were lower than those in the cell line group (42.3%) ( P<0.05), while the pseudocapsule penetration rate in the solid tumor slices (50.0%) were higher than those in the cell line group (23.1%) ( P<0.05). No difference was found of pseudocapsule invasion rate between two groups ( P>0.05). Neoplasm invasion type in ovary changed with tumor planting time. High proportion of pseudocapsule type was found at the beginning of tumor planting, and the pseudocapsule penetration rate raised with tumor planting time increased. High proportion of pseudocapsule type was also found in patients with FIGO stageⅠepithelial ovarian cancer, and pseudocapsule penetration rate increased in those with FIGO stageⅡ. No difference in neoplasm invasion type was found between two kinds of pathological types ( P>0.05). Conclusions:There are differences between the two kinds of orthotopic models established with human epithelial ovarian cancer solid tumor tissue slices and human ovarian carcinoma cell line OVCAR-3. Compared to the solid tumor slices model, the cell line model is more stable for the follow-up study. The proportion of three neoplasm invasion types in ovary were more balanced in 8 weeks after tumor planting, and 8 weeks after tumor planting is the best start time for the follow-up experiment.

Application of mobile extracorporeal membrane oxygenation in inter-hospital transport of pediatric acute respiratory distress syndrome: Retrospective studies for 7 case / 解放军医学杂志

Objective: To investigate the application and safety of mobile extracorporeal membrane oxygenation (ECMO) in inter-hospital transport of pediatric patients with acute respiratory distress syndrome (pARDS). Methods: Data were retrospectively collected of children with pARDS transported by mobile ECMO from Jan. 1, 2019 to Nov. 25, 2019. All children suffered from severe ARDS, and the curative effect in their local hospital was not good, the disease was still progressing after traditional conservative treatments such as mechanical ventilation (MV), small tidal volume protective ventilation, prone position ventilation, and fluid restriction, and the severity of the disease reached the applicable ECMO indications. The age, sex, clinical manifestations, ECMO transfer time, ECMO transfer distance, ECMO duration, MV duration, length of hospital stay, prognosis and complications were collected and analyzed. Results: Seven pediatric patients were included in present study including 6 males and 1 female, aged (43.3±42.9) months, body weight (18.4±17.7) kg, ECMO travel distance (9.4±8.9) km, and ECMO travel time (5.7±17.2) min. After arriving in the Guangdong Provincial People's Hospital, 6 pediatric patients (4 were cured and 2 died) were discharged and 1 pediatric patient was still being treated. The MV duration was (17±11) d, ECMO duration was (307.4±233.6) h, and the length of hospital stay was (23±15) d. Of the 7 pediatric patients, 4 were caused by adenovirus infection, and the other 3 cases were infected by unclear pathogenic bacteria. The cause for death was severe sepsis shock combined with severe heart dysfunction and severe pulmonary hemorrhage. Conclusions: With a skilled ECMO teams, mobile ECMO may provide a safe and effective inter-hospital transport of pARDS patients. Mobile ECMO provides a good way to treat children patients with respiratory critical condition.

A preliminary study of long-term mitochondrial dysfunction in rat brain caused by lipopolysaccharide-induced sepsis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To preliminarily investigate the long-term structural and functional injuries of mitochondria in rat brain caused by sepsis.</p><p><b>METHODS</b>Wistar rats were randomly assigned into sepsis and control groups. A rat model of sepsis was prepared by an intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS) of gram-negative bacteria, and the survival assay was performed. Eight rats in the sepsis group were sacrificed at 12, 24, 48, or 72 hours after LPS injection, while rats in the control group were sacrificed after an intraperitoneal injection of an equal volume of normal saline. Mitochondria were extracted from rat brain tissue. Mitochondrial membrane potential (MMP) and mitochondrial swelling level were determined by flow cytometry, and the activities of electron transport chain complexes (I-V) were measured using enzyme assay kits. Hematoxylin-eosin (HE) staining and electron microscopy were used to observe morphological changes in brain tissue and mitochondria.</p><p><b>RESULTS</b>The sepsis group had a significantly lower survival rate than the control group (P<0.01). The MMP and activities of electron transport chain complexes (I-V) in the sepsis group, which were significantly lower than those in the control group (P<0.05), were reduced to the lowest levels at 48 hours and partially recovered at 72 hours. The mitochondrial swelling level in the sepsis group, which was significantly higher than that in the control group (P<0.05), increased to the peak level at 48 hours and partially recovered at 72 hours. Hematoxylin and Eosin staining revealed substantial damages in the structure of brain tissue, and electron microscopy showed mitochondrial swelling, and vacuolization in a few mitochondria.</p><p><b>CONCLUSIONS</b>In the rat model of LPS-induced sepsis, both structural and functional injuries are found in cerebral mitochondria, and achieve the peak levels probably at around 48 hours.</p>

Study on the long-term trend of suicidal deaths in Macheng of Hubei province, 1984-2008 / 中华流行病学杂志

Objective To explore the characteristics and the long-term trend of suicidal deaths among the rural population in Hubei province. Methods Data on suicide deaths from 1984 through 2008 were released from Macheng Death Registration System and analyzed by year, gender and age. Results The suicidal death rates were decreasing during the last 25 years in Macheng city, with the standardized suicide mortality rapidly decreasing from 113.29/100 000 in 1984 to 20.11/100 000 in 2008. The proportion of suicide deaths in the total deaths caused by injuries were declining but not obviously. Suicide was still the leading cause of deaths among all the deaths due to injuries.Number of suicidal deaths among females was outnumbered the males during the last 25 years,representing 50%-60% in total suicide deaths annually. The proportion of suicide deaths among the elderly aged 65 and over had significantly increased in the recent years, which accounting for 46.81% of all the suicidal deaths in 2008. Conclusion Suicide remained the leading cause of injury deaths among the population in this area, especially in females. Attention should be paid to the females and the elderly aged 65 and over,in the rural areas.