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 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 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 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 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.

Objective To establish the reference ranges of preductal oxygen saturation (SpO2) and heart rate (HR) for healthy neonates in 10 minutes after birth. Methods SpO2 and HR recordings of 203 term neonates (vaginal group:n=97 and ce-sarean group:n=106) with regular respiratory pattern were evaluated. 10th-95th percentile charts of SpO2 and HR from 1 minute to 10 minutes after birth were drawn. Results The SpO2 of P10, P50 and P95 at 1 minute after birth was 62%, 71%and 85%respec-tively. The heart rate of P10, P50 and P95 at 1 minute after birth was 66 bpm, 98 bpm and 126 bpm respectively. The median time for SpO2 to reach 90%was 5 minutes. The rising trend of HR was evident during 1-5 minutes after birth, and then the HR leveled off. Conclusions The status of newborn can be assessed using the charts of SpO2 and HR combined with clinical manifestations. The oxygen intervention should be used with care to avoid damage caused by hyperoxemia and hypoxemia.

Objective To investigate the interference effect of baicalin on acute brain injury induced by aconitine in rats and its mechanism. Methods A total of 200 Sprague-Dawley(SD)rats were randomly divided into five groups:normal control,baicalin control,aconitine poisoning,baicalin 15 mg/kg intervention and baicalin 30 mg/kg intervention groups(each,n=40). Aconitine(20μg/kg)was given via tail vein in aconitine poisoning group. The rats in the normal control group and baicalin control group were respectively injected with saline 2 mL/kg and baicalin 30 mg/kg via tail vein. The aconitine poisoning rats were given with baicalin at the dose of 15 mg/kg and 30 mg/kg respectively in the low and high dose baicalin intervention groups within 2-3 minutes after injection of aconitine. Rats in all groups in the study were anesthetized and sacrificed at 1,6,12,24 hours after various agents were respectively given in the groups,the rat cerebral cortex samples were collected,the histological changes in normal and baicalin control groups and pathological changes of the aconitine poisoning rats were observed,the levels of glutamate(Glu),aspartate(Asp),γ-aminobutyric acid(GABA),glycine(Gly)were detected and the apoptotic cells were determined at the above time points. Results Compared with the normal control group,the aconitine poisoning group had significantly higher levels of excitatory amino acids Glu and Asp and the number of apoptotic neurons. After exposure to aconitine for 1 hour, the levels of inhibitory amino acids of GABA and Gly were markedly decreased in the rat cortex in the poisoning group compared to the normal control group(both P<0.05),at 6 hours and 12 hours they were significantly increased and after 24 h,they began to decline,but still maintained at relatively high levels. Compared with the aconitine poisoning group, after baicalin intervention for 1 hour,in the 15 mg/kg and 30 mg/kg baicalin intervention groups,the levels of Glu and Asp were markedly decreased〔Glu(μmol/L):309.39±14.59,307.22±23.69 vs. 370.46±40.31,Asp(μmol/L):143.43±8.36,129.12±4.86 vs. 222.97±6.26〕,while the levels of GABA and Gly were increased〔GABA(μmol/L):55.91±4.76,59.61±13.11 vs. 32.05±2.20,Gly(μmol/L):32.33±1.85,33.90±0.66 vs. 21.96±4.75〕,and the number of neuronal apoptosis was obviously decreased(cell/mm2:18.65±4.10,14.80±1.89 vs. 58.15±3.68,both P<0.05). Under microscope and electron microscope,the pathological and ultrastructural changes indicated that the aconitine poisoning group had the most marked cerebral cortex damage at 12 hours after poisoning,while the two baicalin intervention groups showed milder damage than that in aconitine poisoning group. Conclusions The neural toxic effect of aconitine in rats may be related to the imbalance between the neurotransmitter contents of excitatory Glu. Asp and inhibitory GABA,Gly in the cerebral cortex. Baicalin can decrease the contents of excitatory amino acid and elevate the inhibitory amino acid,therefore it may ameliorate the cerebral injury of acute aconitine intoxication in rats.