ABSTRACT
In recent years, the development of bispecific antibodies (bsAbs) has been rapid, with many new structures and target combinations being created. The boom in bsAbs has led to the successive issuance of industry guidance for their development in the US and China. However, there is a high degree of similarity in target selection, which could affect the development of diversity in bsAbs. This review presents a classification of various bsAbs for cancer therapy based on structure and target selection and examines the advantages of bsAbs over monoclonal antibodies (mAbs). Through database research, we have identified the preferences of available bsAbs combinations, suggesting rational target selection options and warning of potential wastage of medical resources. We have also compared the US and Chinese guidelines for bsAbs in order to provide a reference for their development.
ABSTRACT
Hematopoietic stem cell (HSC) transplantation is the only curative therapy for many diseases. HSCs from umbilical cord blood (UCB) source have many advantages over from bone marrow. However, limited HSC dose in a single CB unit restrict its widespread use. Over the past two decades, ex vivo HSC expansion with small molecules has been an effective approach for obtaining adequate HSCs. Till now, several small-molecule compounds have entered the phase I/II trials, showing safe and favorable pharmacological profiles. As HSC expansion has become a hot topic over recent years, many newly identified small molecules along with novel biological mechanisms for HSC expansion would help solve this challenging issue. Here, we will give an overview of HSC biology, discovery and medicinal chemistry development of small molecules, natural products targeting for HSC expansion, and their recent clinical progresses, as well as potential protein targets for HSC expansion.
ABSTRACT
Objective To investigate the effect of sevoflurane preconditioning on CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP) expression in the cerebral cortex after focal cerebral ischemiareperfusion (I/R) injury in rats and the mechanism. Methods Thirty-six male SD rats weighing 250-280 g were randomly divided into 3 groups ( n = 12 each) : sham operation group (group S) , focal cerebral I/R group (group I/R) and sevoflurane preconditioning group (group Sevo-pc). The animals were anesthetized with intraperitoneal chloral hydrate 300 mg/kg. In groups I/R and Sevo-pc, focal cerebral ischemia was induced by middle cerebral artery occlusion using a nylon thread with rounded tip inserted into the right internal carotid artery and advanced cranially until resistance was met. The occlusion was maintained for 1 h followed by 24 h reperfusion. Group Sevo-pc inhaled 2.7% sevoflurane for 1 h before ischemia. Neurological deficits were assessed and scored at the end of 24 h reperfusion and then the rats were decapitated. Their brains were immediately removed. The cerebral infarct size was determined by TTC staining. The CHOP expression in the ischemic cerebral cortex was determined by immunohistochemistry. The number of apoptotic neurons was counted using TUNEL. Results The neurological deficit scores were significantly higher, the cerebral infarct size was significantly larger, and the CHOP expression and the number of apoptotic neurons were significantly higher in groups I/R and Sevo-pc than in group S ( P ＜ 0.01) . The neurological deficit scores were significantly lower, the cerebral infarct size was significantly smaller, and the CHOP expression and the number of apoptosis neurons were significantly lower in group Sevo-pc than in group I/R ( P ＜ 0.05 or 0.01) . Conclusion Sevoflurane preconditioning may protect the brain against focal cerebral I/R injury by down-regulating CHOP expression in the cerebral cortex in rats.
ABSTRACT
Objective To investigate the methods of anesthesia,infusion and the skill of removing urinary calculus for the treatment of uretemlith stones using ureterescope air pressure path lithoclasty.Methods Six hundred and ninety ureterolith stone patients using ureterescope air pressure path lithoclasty,383 patients were anesthetized by single sacro-anesthesia,and the diclofenac sodium suppositories were added in 312 cases to strengthen the anesthesia effeets.Antegrade perfusion with furosemide in the operation was used.Results Broken the stones in orthophoria were successful in 645 patients.the total success rate Was 93.5%and the total rate of removing urinary calculus was 93.8%.Conclusions Ureteroscope air pressure path lithoclasty is high efficiency,safety and easy manipulation.It is a satinfactory method for the treatment of ureterolith stones,and the correct method of anesthesia and infusion perfect skill of removing urinary calculus can improve the rate of removing urinary calculus and decrease the costs.