Protein phosphorylation is an important post‐transcriptional modification involving an extremely wide range of intracellular signaling transduction pathways, making it an important therapeutic target for disease intervention. At present, numerous drugs targeting protein phosphorylation have been developed for the treatment of various diseases including malignant tumors, neurological diseases, infectious diseases, and immune diseases. In this review article, we analyzed 303 small‐molecule protein phosphorylation kinase inhibitors (PKIs) registered and participated in clinical research obtained in a database named Protein Kinase Inhibitor Database (PKIDB), including 68 drugs approved by the Food and Drug Administration of the United States. Based on previous classifications of kinases, we divided these human protein phosphorylation kinases into eight groups and nearly 50 families, and delineated their main regulatory pathways, upstream and downstream targets. These groups include: protein kinase A, G, and C (AGC) and receptor guanylate cyclase (RGC) group, calmodulin‐dependent protein kinase (CaMK) group, CMGC [Cyclin‐dependent kinases (CDKs), Mitogen‐activated protein kinases (MAPKs), Glycogen synthase kinases (GSKs), and C dc2‐like kinases (CLKs)] group, sterile (STE)‐MAPKs group, tyrosine kinases (TK) group, tyrosine kinase‐like (TKL) group, atypical group, and other groups. Different groups and families of inhibitors stimulate or inhibit others, forming an intricate molecular signaling regulatory network. This review takes newly developed new PKIs as breakthrough point, aiming to clarify the regulatory network and relationship of each pathway, as well as their roles in disease intervention, and provide a direction for future drug development.
Introduction Transurethral seminal vesiculoscopy (TSV) is a common treatment for obstructive azoospermia but has a high rate of recurrence. Aim Introduce a new method involving indwelling double-J (D-J) tubes in seminal vesicles during TSV in order to reduce recurrent rate and refractory obstructive azoospermia. Methods A prospective study was performed to compare the effects and complications of patients treated with or without indwelling D-J tubes after TSV. General information and TSV Surgical parameters, including age, body mass index, preoperational antibiotics, history of urinary tract disease, surgical time length (STL) and complications during and after the surgery, were collected and used as baseline information. The current study compared the postoperative complications and postoperative hospital days (PHD), as well as the recurrence rate of haemospermia between the two groups. Results A total of 59 cases, including 28 patients who underwent treatment with indwelling D-J tubes and 31 patients who underwent treatment with the standard TSV procedure, were enrolled in this study. There was no statistically significant difference in baseline data, Intraoperative and postoperative complications and postoperative hospital days between the two groups (p > 0.05), and there was a statistically significant difference in STL and recurrence rate between the two groups (p < 0.05), the recurrence rate was lower in D-J group (21.4%) than that of control group (41.9%). This technique can effectively suppress the appearance of the first recurrence peak after TSV. Conclusion We introduced a new technique of indwelling D-J tubes for TSV to reduce the recurrence rate and refractory obstructive azoospermia.
Objective To introduce a new sequential sheath urethral dilatation (SSUD) method to treat male short segment posterior urethral stricture (MSS-PUS). Methods 67 male patients who had a MSS-PUS were enrolled and randomly assigned to one of two groups: group A (SSUD) and group B (Cold knife internal urethrotomy, CIU). Baseline information, including age, diabetes status, location of urethral stricture, preoperative ultrasound post-void residual (PVR) measurement, preoperative maximum urinary flow rate (Qmax), and preoperative International Prostate Symptom Score (IPSS) were collected and compared between groups. The operation time, postoperative length of hospital stay, indwelling catheter size, success rate, operative complications, recurrence, postoperative PVR, Qmax, and IPSS were evaluated and compared between the two groups. Results There was no significant difference in the baseline data, postoperative data, the complication, recurrence rates, postoperative length of hospital stay and postoperative PVR measurements between the two groups (p > 0.05), but the difference in immediate success rate, operative time, indwelling catheter size, postoperative Qmax and postoperative IPSS was statistically significant (p < 0.05). Conclusion We introduced a new SSUD method to treat MSS-PUS. The immediate success rate, operation time, and surgical effect were better than the CID procedure.
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