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 compare the effect of urapidil at different doses on blood pressure and prognosis of patients with acute ischemic stroke (AIS) so as to provide data evidence for its clinical use.Methods: Totally 62 patients with AIS were divided into 3 groups in a prospective study: 20 cases in high dosage group, 21 cases in middle dosage group and 21 cases in low dosage group.All the patients were treated with urapidil and urokinase, and the initial dose of urapidil was 25 mg, 15 mg and 5 mg, respectively.Systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the patients before and after the treatment were observed, and the US national institutes of health stroke scale (NIHSS), modified Rankin scale (mRS) and activity of daily living scale (ADL) were also evaluated in the follow-ups.Results: The time of blood pressure up to standard in the middle dosage group and low dosage group was longer than that in the high dosage group.At the same time, the time of blood pressure up to standard in the low dosage group was longer than that in the middle dosage group, and the difference had statistical significance (P＜0.05).After the treatment, SBP and DBP at T1 in all the groups were notable lower than those at T0,and those at T2 and T3 were lower than those at T1, and the differences had statistical significance (P＜0.05).After the treatment, the SBP and DBP levels in the high dosage group were lower than those in the middle dosage group and low dosage group, and those in the middle dosage group were lower than those in the low dosage group, and the differences had statistical significance (P＜0.05).The NIHSS, mRS and ADL scores of the middle dosage group were lower than those of the low dosage and the high dosage group (P＜0.05), and there was no significant difference between the latter two groups (P＞0.05).Conclusion: With the initial dose of 15 mg, urapidil can ensure good prognosis on the premise of effective decompression.

Professor ZHOU Yun-xian's clinical experience of acupuncture combined with Chinese material medica for xerophthalmia is introduced. Her treatment for xerophthalmia is firstly focused on syndrome differentiation, indicating that different syndrome has different treatment of acupuncture and Chinese material medica. It is emphasized that by following the holistic concept of TCM, the local acupoints and whole-body acupoints cooperate closely, forming her special combination method of acupoints. In clinic, attention is focused on the application of many acupuncture techniques and extra points. With the combination of acupuncture and Chinese material medica, the treatment is flexible with superior clinical efficacy.
Acupuncture Therapy ; Combined Modality Therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Xerophthalmia ; drug therapy ; therapy

OBJECTIVE To investigate the expression differences of seven cytochrome P450 (CYP) isoforms between L02, LX-2 and HepG2 cells and identify the most suitable cell type for different CYP researches. METHODS L02, LX-2 and HepG2 cells were treated with omeprazole (Ome), dexamethasone(Dex), phenobarbital sodium (Phe), isoniazid (Iso) and rifampicin (Rif) at 5, 10, 20 and 40 μmol • L-1. Cell viability was analyzed by CCK-8 assay. The gene expressions of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 in LX-2 cells were assessed by real-time quantitative PCR (RT-qPCR). The protein expressions of these seven CYP isoforms in L02, LX-2 and HepG2 cells were assessed by Western blotting. Furthermore, CYP3A4 activity in the three types of cells treated with Rif 5, 10, 20 and 40 μmol • L-1 for 24 h was validated by Luciferin-PFBE. RESULTS Cell viabilities of all the three hepatocytes were over 80% when exposed to Ome, Dex, Phe, Iso and Rif (≤40 μmol • L-1) for 24 h. According to the RT-qPCR, Phe could significantly enhance the gene expressions of CYP2B6 (P<0.05) and CYP2D6 (P<0.01) in LX-2 cells. The results of Western blotting exhibited protein expression differences of seven CYP isoforms between L02, LX-2 and HepG2 cells treated with Ome, Dex, Phe, Iso and Rif (≤40 μmol-L-1) for 24 h. CYP2C9 [Integrated absorbance (IA)=1.58±0.07], CYP2C19 (IA= 0.95±0.03) and CYP3A4 (IA=1.29±0.05) had higher expression abundances in L02 cells, CYP2B6 (IA= 1.48±0.01) and CYP2D6 (IA=1.46±0.02) in LX-2 cells, and CYP1A2 (IA=1.62±0.19) and CYP2E1 (IA= 1.49±0.10) in HepG2 cells. Additionally, CYP3A4 activity in L02, LX-2 and HepG2 cells could not be up-regulated by Rif. CONCLUSION The most suitable cell type for different CYP researches is L02 for CYP2C9, CYP2C19 and CYP3A4, LX-2 for CYP2B6 and CYP2D6, HepG2 for CYP1A2 and CYP2E1, respectively.

Background Choroidal neovascularization (CNV) is the primary pathogenic cause of many fundus diseases.Oxidative stress injury of retinal pigment epithelial (RPE) cells plays important role in angiogenesis of choroid new blood vessels.Oxidative stress injury can active p75NTR receptor, a member of tumor necrosis factors family,resulting in the proliferation of vascular endothelial cells.However, the mechanisms of vascular endothelial cell proliferation remain unclear.Objective This study was conducted to investigate the effect of p75NTR overexpression on CNV and the relative mechanism.Methods The ARPE-19 cell line was used in this study.RPE cells were transfected with p75NTR receptor overexpressed plasmid, and untransfected cells served as the control group.The transfected results were verified by reverse transcription-PCR and Western blot assay.Viability of the cells over time was determined in the p75NTR receptor plasmid transfected group by using BrdU assay.The percentage of apoptotic cells was detected by flow cytometry using Annexin V-FITC/PI fluorescence staining.The percentage of reactive oxygen species (ROS) expression in the cells was detected by using H2 DCFDA fluorescence and flow cytometry.Mitochondrial membrane potential and cytochrome C expression were examined under the confocal microscope.The protein expressions of cleaved caspase-3, Fas and VEGF were determined by Western blot assay.Results The relative expression level of p75 NTR receptor mRNA was (6.11 ±0.77) times higher than that of the control group, and relative expression level of p75NTR receptor protein in the cells in the p75NTR receptor plasmid transfected group was (7.42±0.48) times higher than that in the control group (t=11.49 and 23.17 ,both at P＜0.01).The absorbency values of the p75NTR receptor plasmid transfected group were (93.12±0.56) ％ , (86.30±0.66) ％ , (72.53-±0.86) ％ and (60.77 ±2.81) ％ in 12,24,36 and 48 hours after plasmid transfection, which were significantly lower than 100％ in the control group, and the apoptotic percentages were evidently higher than that in the control group (all at P＜0.05).The relative fluorescence intensity of ROS fluorescence in the p75NTR receptor plasmid transfected group was 2.4 times higher than that in the control group,showing significant difference (t=16.45, P＜0.01).The positive expressing rate of mitomarker (mitochondrial membrane potentials) was 100％ in the control group and (37.30± 2.06)％ in the p75NTR receptor plasmid transfected group, with significant difference between them (t =57.71,P＜0.01).The fluorescence intensity of cytochrome C expression was elevated in the p75NTR receptor plasmid transfected group compared with the control group.Compared with the control group,the expressing levels of cleaved caspase-3 ,Fas and VEGF165 proteins in the cells were significantly raised in the p75NTR receptor plasmid transfected group (all at P＜0.01).Conclusions Overexpression of p75NTR receptors in RPE cells leads to mitochondrial damage and cellular apoptosis and the secretion of VEGF protein, which sequentially promote CNV.P75NTR receptor may be another important regulation pathway in RPE oxygen damage.

HuangDi NeiJing, the Yellow Emperor's Classic of Internal Medicine, a foundational classic of Chinese medical theory, is ranked as the first among the four most important classics of traditional Chinese medicine. Translation of culture-specific Lexicon is a pivot, also a nodus in translating Huangdi Neijing, so, chewing over it is of important meaning for English translation of the Chinese classic or even for that of whole Chinese medicine. In expectation of somewhat contribution to the development of the Chinese medical English discipline, the classification and translation strategy for culture-specific lexicon were discussed by the authors in this paper through an empirical study on comparing the different terms translated in two versions of Huangdi Neijing translation.
China ; History, Ancient ; Medicine in Literature ; Medicine, Chinese Traditional ; history ; Terminology as Topic ; Translating

Objective:To study the cause of the medical disturbances and its influential factors, to formulate the corresponding prevention strategy and measures. Methods:Total 32 medical disturbances in a hospital were an-alyzed and evaluated. Results:The number of medical disturbances in this hospital was declining. The department of maternity, orthopedic, pediatrics had the most medical disturbances. The compensation for the patients with med-ical disturbances was 2. 18 times as the patients without medical disturbances. Conclusion:It should be clear the causes of the medical disturbances and countermeasures should be proposed according to the reasons, rationally re-solve doctor-patient conflicts.

Objective To understand the influencing factors of the post competency of health technical personnel in township hospitals in a prov-ince,so as to provide scientific reference for improving health professionals'post competency. Methods Using stratified cluster random sam-pling,1242 health professionals from township health centers and village clinics of 14 cities were extracted and then surveyed with questionnaire. Results The average score of the respondents'post competency was 3.43,which meant they could afford most of the work. Multiple linear re-gression analysis showed that the main influencing factors of the professionals'post competency included gender,age,specialty,and training. The female,senior,nursing and health-care professionals with training exhibited a better post competency. Conclusion To realize the further develop-ment of professionals'post competency,medical students should not only be early clinical and more clinical,but also actively participate in the training and continue the education after entering the clinic. On the other hand ,the government should define the function orientation of the town-ship healthy centers and explore human resource management mode based on the post competency.

OBJECTIVE: To study the effect of Danshen injection and Xinkeshu tablets on the metabolism of CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 in rabbits by cocktail probe substrates method. METHODS: Sixteen healthy fasted male rabbits were simultaneously given cocktail probe substrates including caffeine, tolbutamide, omeprazole, dextromethorphan and midazolam. The metabolic rates of cocktail probe substrates were determined by LC MS/MS methods at some specific time following the administration. Then the rabbits were randomly assigned to receive either Danshen injection or Xinkeshu tablets. The whole self-control trial was consisted of 3 cycles. The low, middle and high dosage (0.5, 1 and 2 mL · kg^-1) of Danshen injection group would be administrated in 3 cycles in sequence. The low, middle and high dosage (90, 180 and 360 mg · kg^-1) of Xinkeshu tablets group would be administrated in 3 cycles in sequence. Each cycle includes wall-out period of 7 d followed by administration of the 2 herbal medicines for consecutive 7 d. On the 15th day the cocktail probe substrates were administrated and the metabolic rates were determined. The differences of the metabolic rates between after and before admininstration of the 2 herbal medicines were assessed by one-way analysis of variance (ANOVA). RESULTS: After taking the agents of Danshen injection and Xinkeshu tablets, the metabolic rates of the five cocktail probe substrates had a tendency to decline compared with the before-administration. CONCLUSION: The outcome in vivo is in accordance with that in vitro. Danshen injection and Xinkeshu tablets can inhibit the metabolism of five CYPs (1A2, 2C9, 2C19, 2D6 and 3A4) activities in rabbits. At sometimes precautions are needed to co-administrate either Danshen injection or Xinkeshu tablets for-possible herb-drug interactions.

Humans ; Estazolam ; Chromatography, High Pressure Liquid