The FDA approved a total of 37 new drugs in 2022, including 22 new molecular entities and 15 new biological products. This is the year with the lowest number of new drugs approved by the FDA since 2017. Among these approved drugs, 21 new drugs belong to the "first-in-class" category, accounting for 56% of the total approved drugs, which is the highest ratio in the past 10 years. Among the drugs approved in 2022, there are 5 small molecule kinase modulators, including the tyrosine kinase 2 (TYK2) allosteric inhibitor deucravacitinib, the first oral pyruvate kinase (PK) activator mitapivat, the Janus kinase 1 (JAK1) selective inhibitor abcrocitinib, the JAK2 selective inhibitor pacritinib and the broad-spectrum fibroblast growth factor receptor (FGFR) inhibitor futibatinib. This review briefly describes the discovery background, research and development process, synthesis routes and clinical efficacy and safety of small molecule kinase modulators approved by the FDA in 2022, hoping to provide ideas and methods for further research on kinase modulators.

Acute Disease ; Female ; Humans ; Infant ; Infant, Newborn ; Propionates ; blood ; Pyruvate Carboxylase Deficiency Disease

Objective　To summarize the treatment of 7 cases of severe coronary artery disease with CO2 laser transmyocardial revascularization(TMLR).　Methods　The mean preoperative angina class (Canadian Cardiovascular Society, CCS), number of diseased coronary arteries were 3.6±0.7 and 2.8±0.6 respectively. All the patients underwent left anterolateral thoracotomy through the fifth intercostal space under general anesthesia, the left ventricule was exposed and then TMLR was performed. The mean channels in TMLR was 32.5. 　Results　The symptoms of angina disappeared during the first postoperative month, with no relapse reported in the first follow-up year. There was significant difference in the angina class (P＜0.05), ejection fraction also increased. The ischemia region of the heart decreased through the single photon emission computed tomographic(SPECT) test.　Conclusion TMLR can relieve angina and improve life quality of patients with severe coronary artery disease. It can accelerate the recovery of dormant myocardium and enhance the contractility.

Adult ; Deglutition ; Humans ; Laryngeal Diseases ; Male ; Pharynx

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Humans ; Imaging, Three-Dimensional ; Male ; Maxillary Artery ; diagnostic imaging ; Middle Aged ; Pterygopalatine Fossa ; diagnostic imaging ; Tomography, Spiral Computed ; Young Adult

Humans ; Infant, Newborn ; Meconium ; Peritonitis ; etiology

Adolescent ; Arterial Occlusive Diseases ; complications ; Behcet Syndrome ; complications ; Humans ; Hypertension ; etiology ; Hypertensive Encephalopathy ; etiology ; Male

Objective To examine the expression of follistatin-like protein 1 (FSTL1) in the peripheral blood and intestinal mucosa tissues of ulcerative colitis (UC) patients and analyze the correlation between its expression and the activity of UC.Methods From October 2010 to June 2012,sixty patients with UC were collected.From April 2012 to October 2012,thirty individuals without any obvious mucosa lesion under colonoscope and confirmed by pathological examination were set as control group.The serum expression level of FSTL1 of both UC group and control group were determined by enzyme linked immunosorbent assay (ELISA).t-test was performed for comparison between groups.The expression of FSTL1 in the intestinal mucosa of UC group and control group was detected by immunohistochemistry.Chi-square test was used for comparison between groups.The patients with UC were scored with ulcerative colitis disease activity index (UCDAI).Its correlation with plasma FSTL1 was analyzed by Pearson correlation coefficient.Results The serum expression level of FSTL1 of UC group ((14.37-±-1.80) μg/L) was higher than that of control group ((5.80±0.72) μg/L)and the difference was statistically significant (t=25.01,P＜ 0.05).The serum expression level of FSTL1 of UC group was positively correlated with UCDAI (r=0.814,P＜0.05).The positive expression rate of FSTL1 in the intestinal mucosa tissues of UC group (86.7％,52/60)was higher than that of control group (46.7％,14/30) and the difference was statistically significant (x2 =52.334,P＜0.05).Conclusions The expression of FSTL1 of UC patients increases and is positively correlated with disease activity.FSTL1 may play a role in the development of UC.

Objective To investigate the dynamic changes of glutamic acid(Glu) levels,ATP levels,free calcium ion,mitochondrial membrane potential,apoptosis related to mitochondrial pathways of apoptosis and Na+-K+-ATPase activity,and explore the mechanism of mitochondrial pathways of apoptosis in neuron injury of rats with kainite acid(KA)-induced epilepsy.Methods KA-induced epilepsy model was induced by injection of KA into the hippocampus.Forty SD rats were randomly divided into 2 groups: control group(n=8)and KA group(6 h,1 d,3 d,7 d,n=8).The concentration of Glu in hippocampus CA3 area was detected by high performance liquid chromatography.The apoptosis of hippocampus neurons and the concentration of Ca2+ were assayed by flow cytometry.The mitochondrial membrane potential was detected by JC-1.The Na+-K+-ATPase activity was examined.Results 1.The concentration of Glu in hippocampus increased at 3 d after KA injection and reached the peak after 7 d injection.2.The concentration of Ca2+ level,mitochondrial membrane potential,and the number of apoptosis neurons were significantly increased,wherase the mitochondrial membrane potential decreased after 6 h of KA injection,7 d after KA injection,and the changes were more severe.3.In the hippocampus,the activities of the Na+-K+-ATPase significantly decreased at 1 d after KA injection,and they decreased more over at 7 d after KA injection.4.The levels of ATP,mitochondrial membrane potential,and the activity of the Na+-K+-ATPase were negatively correlated with the neuron apoptosis(Pa

Background Trans-scleral fixation of intraoculalen(IOL) hamade greaprogress,buthe long-term stability of the implanposition of IOL aftesurgery inoideal.Objective Thistudy wato investigate the relevanfactorof IOL dislocation aftetrans-scleral fixation of IOL.Methodrespective case-observational study wadesigned.The clinical datfrom 321 eyeof 321 patientwho had received trans-scleral fixation of IOL were collected.total of 263 patientcompleted the effeetive follow-up,and 164 patientwith the follow-up fomore than 5 years.No IOL dislocation occurred within 5 yearin all 263 eyes.The relationship between IOL material,IOL implantation location,the time of IOL dislocation and the intraoculapressure with IOL dislocation were analyzed.ResultIOL dislocation appeared 7-10 yearaftesurgery in 9 eyewith an incidence rate of 5.49％.Breakage of IOL suture wafound in all the eyewith IOL dislocation.Dislocation wamore frequently found in IOL performed in the oblique position than thain the horizontal position (10.0％ vs.3.5％).The rate of IOL dislocation wahighesin traumatiretinal detachmeneyes,apercentage of 33.33％.Single piece IOL wamore easily dislocated.ConclusionThe breakage of anchosuturein IOL ileading cause of IOL dislocation aftetrans-scleral fixation of intraoculalens,which may be associated with the weighresulting from the fixation procesin non-level angulaIOL.Iirecommended thaIOL should be fixed in the horizontal position.