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.

Objective To analyze the clinical characteristics of hospital acquired mycotic pneumonia in elderly patients (aged≥ 80 years).Methods The clinical data were reviewed on 64 cases of elderly patients aged 80-93 years with hospital-acquired infection of mycotic pneumonia from June 2007 to July 2011.According to the results of sputum culture,therapy plan was made and antibiotic drugs were selected.Results Among these 64 patients,Candida mycoderma (62.5 ％,40 cases) occupied the first place and C.glabrata (20.3％,13 cases) was the second place (x2 =127.50,P＜0.01).Their chest x-ray or CT films were not characteristic,but lamellar shadows (68.8％,44cases) and cotton-like shadows (40.6 ％,26 cases) were found in the majority.60 cases (93.8 ％ ) of these patients had more than 3 complications,and 58 cases (90.6％) of them took over 2 kinds of antibiotics.The improvement rate of these patients was 81.3％ (52 cases)and mortality rate was 18.8％(12 cases).Conclusions Elderly patients (aged≥ 80 years) with hospital acquired infection of mycotic pneumonia have high incidence and mortality rate.The key point to cure is to make an early diagnosis and treat them as early as possible.

Objective To study the association of single nucleotide polymorphisms (SNPs) of solute carrier family 22 member 4 (SLC22A4) and SLC22A5 genes with Crhon's disease (CD) in Chinese Han nationality. Methods SNPs in the entire coding region of SLC22A4 and SLC22A5 genes were screened by direct DNA sequencing in 80 CD patients and 80 healthy subjects, and statistical in Han population. Five SNPs were found in entire coding region (2 in SLC22A4 gene and 3 in distribution of the alleles and genotypes of SLC22A4 and SLC22A5 polymorphisms between CD patients and healthy controls. Conclusion There is no correlation of SLC22A4 and SLC22A5 with CD in Chinese Han nationality.

Objective To explore the effect of dimethylformamide(DMF)on the histological structure and enzymes activity in the testis of mice.Methods The KM male mice were treated with DMF by gavage at the doses of 0,0.5,1 and 2 g/kg respectively, once a day,for 30 consecutive days.On day 31,the mice blood samples were collected through eyes and then the mice were killed. Two mice were randomly selected in each group and one testicle was sampled to do the pathological examination,the other one for enzyme activity determination,including succinic acid dehydrogenase(SDH),lactate dehydrogenase(LDH)and acid phosphatase (ACP).Results Compared with the control group,all treated groups showed a significant decrease in body weight(P

BACKGROUND: There is no study addressing transplantation of umbilical cord mesenchymal stem cells for the treatment of spinocerebellar ataxia.OBJECTIVE: To study the clinical effect of human umbilical cord stem cells transplantation in the treatment of autosomal dominant spinocerebellar ataxias. METHODS: Spinocerebellar ataxias patients selected from Stem Transplantation Center of the 455 Hospital of Chinese PLA were treated with umbilical cord mesenchymal stem cells transplantation via intrathecal injection. The number of umbilical cord mesenchymal stem cells was 107 per transplantation, once per week, for 4 weeks.RESULTS AND CONCLUSION: Both the total score of the International Cooperative Ataxia Rating Scale and Activities of Daily Living score were significantly decreased at 1 month after transplantation compared with before treatment (P < 0.05). The nerve function was significantly improved and the total effective rate was up to 16.7%. Experimental findings indicate that, transplantation of umbilical cord mesenchymal stem cells via intrathecal injection is a feasible and effective treatment to ameliorate the clinical efficacy of spinocerebellar ataxias patients and improve their quality of life.

Objective To investigate the association of body mass index(BMI)with metabolic status and chronic complications in newly-diagnosed Chinese type 2 diabetic patients.Methods A total of 515 newly- diagnosed adults type 2 diabetic patients were categorized into underweight(BMI

Objective To compare the changes in serum levels of high sensitive C-reactive protein (hs-CRP)and uric acid(UA)before and after atorvastatin treatment for the patients with both essential hypertension and hypercholesterolemia,and to evaluate its effects on blood pressure and left ventricular remodeling.Methods One hundred and twenty-six hypertensive patients complicated with hypercholesterolemia were randomized into group A with amlodipine 10 mg/d(n = 65)and group B with amlodipine 10 mg/d plus atorvastatin 20 mg/d(n = 61),for three months continuously.Serum levels of total cholesterol(TC),low-density lipoprotein-cholesterol(LDL-C),high-density lipoprotein-cholesterol (HDL-C),triglyeerides(TG),hs-CRP and UA,as well as blood pressure,were determined for both groups before and after treatment.Left ventricular posterior wall thickness(LPWT)and interventricular septum thickness(IVST)were measured by echocardiography and left ventricle mass index(LVMI)was calculated.Results Serum levels of TC,LDL-C,HDL-C,TG,hs-CRP and UA decreased significantly in gr6up B after three-month treatment with atorvastatin,while serum level of HDL-C increased significantly. And,systolic and diastolic blood pressure reduced in both groups,but significantly lower in group B than those in group A,after treatment(P

Objective To investigate the effect of valsartan (angiotensinⅡtypeⅠreceptor antagonists) on neointimal proliferation and expression of CD34 after angioplasty in rabbits.Method Twenty-four male New Zealand White rabbits were randomly divided into three groups:the control group,fed up with common diet;the model group and the valsartan group,fed up with hypercholesterolemic diet for 4 weeks,f then and ballon angioplasty.At 4 weeks after operation,the model group was fed up with common diet,whereas the valsartan group was fed up with the admixture of valsartan 10 mg?kg~(-1)?d~(-1) and common diet.All the rabbits were killed at the end of the 12th weeks.The abdominal aorta was performed with pathologic and morphologic analysis,and expression of CD34 in endothelial cells was analyzed with immunohistochemical method.Results Compared with the model group,the neointimal thickness and area of the valsartan group decreased by 56.58%and 66.81%, respectively.The expression of CD34 of the valsartan group was significantly higher (P

Objective To investigate the in vitro effects of quercitrin on the proliferation and the cytotoxicity of human γδT cells.Methods Peripheral blood mononuclear cells (PBMCs) were isolated from healthy subjects and cultured with isopentenyl pyrophosphate and IL -2 to induce human γδT cells.The hu-manγδT cells were cultured with quercitrin at various concentrations for 48 hours.CCK-8 kits were used to analyze the in vitro proliferation and cytotoxic activities of γδT cells.Flow cytometry was performed to meas-ure the expression of granzyme B and perforin in γδT cells.The expression of p-ERK, p-Akt and Bcl-2 at protein level were detected by Western blot .Results The percentage of human γδT cells in PBMCs was in-creased from (2.96±1.83)%to (88.94±2.36)%after 10 days of culture.The quercitrin at concentrations of 10 to 80 μg/ml could promote the growth of γδT cells and up-regulate the expression of granzyme B , per-forin, p-ERK, p-Akt and Bcl-2 in a dose dependent manner .The cytolytic activities of γδT cells against co-lonic carcinoma cells ( HCT116 ) were enhanced by quercitrin .Conclusion Quercitrin could promote the proliferation of γδT cells and enhance the expression of granzyme B and perforin at certain concentrations in vitro.ERK1/2 and Akt signal transduction systems might be involved in the process .

Objective To investigate the effects and mechanism of huoxuexiaoying tablet on experimental goiter of rats. Methods The rats were randomly divided into six groups: the control, the model control group, huoxuexiaoying tablet at different doses,and the sodium levothyroxine group ( Euthyrox group) . Except for the rats in the control,the rats in other groups were given with propylthiouracil (20 mg·kg-1 ·d-1 ) by intragastric ( i. g. ) administration every day for 60 days. Meanwhile, some rats were treated with huoxuexiaoying tablet at low (4. 4 g·kg-1·d-1),middle (8. 8 g·kg-1·d-1) and high dose (17. 6 g·kg-1 ·d-1 ) orally,and those in the Euthyrox group were given with 7. 8μg·kg-1 ·d-1 Euthyrox by i. g. administration. The rats in the control group were administrated with the same volume of saline (N. S). After 60 days of treatment,the rats were sacrificed,the organ indexes of thyroid and pituitary and the levels of free triiodothyronine ( FT3 )、free thyroxin ( FT4 ) and thyroid stimulating hormone(TSH) in serum,were tested. The expression of basic fibroblast growth factor(bFGF),transforming growth factor-β( TGF-β) and B-cell lymphoma 2 gene ( Bcl-2 ) were examined by immunofluorescence. Results Compared with the model,organ indexes of thyroid were significantly reduced by huoxuexiaoying tablet at three doses (P<0. 05),but not for the pituitary (P>0. 05). The levels of FT3 and FT4 were in a elevating trend,but TSH decreased with no significance (P>0. 05). The morphological structure of thyroid was greatly improved by huoxuexiaoying tablet in comparison with the model. In which the gland dilated,thyroid follicular restored to moderate size,epithelia were cubic or flattened and follicular cavity filled with abundant glial. The expression of bFGF and Bcl-2 decreased significantly (P<0. 01) while TGF-β expression increased notably (P<0. 01). Conclusion Huoxuexiaoying tablet has a great anti-goiter effect,the mechanism of which may be related to promoting thyroid cells apoptosis and inhibiting thyroid cells proliferation.