OBJECTIVE To conduct a clinical rapid evaluation of the marketed proprotein convertase subtilisin/kexin type 9 （PCSK9） inhibitors in China， including evolocumab， tafolecimab， recaticimab， ebronucimab， ongericimab and inclisiran. METHODS Based on the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions （second edition）， drug instructions， clinical diagnosis and treatment guidelines， and literature for six drugs were retrieved from CNKI， Wanfang Data， VIP， PubMed， Embase， Cochrane Library and related official websites. The clinical rapid evaluation was conducted from five aspects： pharmaceutical characteristics， effectiveness， safety， economy， and other attributes. RESULTS The pharmaceutical characteristics， effectiveness， safety， economy， other attributes， and total score of evolocumab scored 24， 27， 15.7， 10， 5.3， and 82 points， respectively. Tafolecimab scored 23.5， 23， 11.5， 9.97， 4.6， and 72.57 points， respectively. Recaticimab scored 20.5， 22， 15.5， 6.37， 3.5， and 67.87 points. Ebronucimab scored 20， 23， 11， 6.48， 3.5， and 63.98 points. Ongericimab scored 20.5， 23， 8.5， 4.83， 3.5， and 60.33 points. Inclisiran scored 25.5， 24， 13， 6.48， 5， and 73.98 points. CONCLUSIONS Evolocumab is the optimal choice for treating hypercholesterolemia and is recommended as the first-line option. Tafolecimab is the second-line option， and recaticimab is suitable for patients who are sensitive to drug adverse reactions. Inclisiran is suitable for patients with poor compliance. Ebronucimab and ongericimab are weakly recommended due to their later market introduction. Clinicians should make individualized drug selections based on factors such as patient risk level and compliance requirements.

Objective To compare the value of ultrashort echo time(UTE)and T1W sequences for detecting bone erosions of gouty arthritis.Methods Forty-four gouty patients were prospectively enrolled,including 32 cases with affected feet and 12 cases with affected knee.MR UTE and T1W sequence scanning of the affected area were performed,and subjectively scoring of imaging quality of 2 kinds of MRI were evaluated,respectively.Then total number and total score of bone erosions of each case were calculated according to all affected bones.Taken DECT as reference standard,the efficacy of UTE and T1WI for detecting bone erosions was assessed through comparing with DECT using Kappa coefficient.Results The imaging quality score of T1WI was lower than that of DECT(all P＜0.05),while no significant difference was found between UTE and DECT(all P＞0.05).There was high agreement between UTE and DECT for detecting bone erosions(κ=0.949),while the agreement between T1WI and DECT ranged from good to high(κ=0.718 to 0.805).The total number and total score of bone erosions based on T1WI were significantly lower than those based on DECT(all P＜0.05),while no significant difference was found between UTE and DECT(all P＞0.05).Conclusion UTE was better than T1WI for detecting bone erosions of gouty arthritis.

Objective To compare the value of ultrashort echo time(UTE)and T1W sequences for detecting bone erosions of gouty arthritis.Methods Forty-four gouty patients were prospectively enrolled,including 32 cases with affected feet and 12 cases with affected knee.MR UTE and T1W sequence scanning of the affected area were performed,and subjectively scoring of imaging quality of 2 kinds of MRI were evaluated,respectively.Then total number and total score of bone erosions of each case were calculated according to all affected bones.Taken DECT as reference standard,the efficacy of UTE and T1WI for detecting bone erosions was assessed through comparing with DECT using Kappa coefficient.Results The imaging quality score of T1WI was lower than that of DECT(all P＜0.05),while no significant difference was found between UTE and DECT(all P＞0.05).There was high agreement between UTE and DECT for detecting bone erosions(κ=0.949),while the agreement between T1WI and DECT ranged from good to high(κ=0.718 to 0.805).The total number and total score of bone erosions based on T1WI were significantly lower than those based on DECT(all P＜0.05),while no significant difference was found between UTE and DECT(all P＞0.05).Conclusion UTE was better than T1WI for detecting bone erosions of gouty arthritis.

Objective:To investigate the application value of Hisense computer-assisted surgery system (CAS) three-dimensional reconstruction in the precision treatment of pediatric liver tumors.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 82 children with liver tumors who were admitted to Affiliated Hospital of Qingdao University from January 2013 to September 2021 were collected. There were 39 males and 43 females, aged 13(19)months. Children underwent upper abdominal dynamic enhanced computed tomography (CT) examination, and three-dimensional reconstruction was performed on CT images of arterial, equili-brium and venous phases with Hisense CAS. Surgical feasibility and scheme were evaluated and conducted based on the results of upper abdominal dynamic enhanced CT examination, and then revised according to three-dimensional reconstruction results of Hisense CAS. Observation indicators: (1) comparison of surgical scheme between two-dimensional enhanced CT images and three-dimensional reconstruction results of Hisense CAS; (2) intraoperative and postoperative situations; (3) follow-up. Follow-up was conducted by outpatient examination to detect postoperative compli-cations and residual liver compensation up to November 2021. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(IQR) or M(range). Count data were described as absolute numbers or percentages. Results:(1) Comparison of surgical scheme between two-dimensional CT images and three-dimensional reconstruction results of Hisense CAS. ① Based on the two-dimensional CT images, 42 cases of 82 children could undergo one-stage resection and 40 children could not. However, based on the three-dimensional reconstruction results of Hisense CAS, 48 cases of 82 children could undergo one-stage resection and 34 children could not. There were 6 children with one-stage resection feasibility based on the three-dimensional reconstruction results of Hisense CAS rather than the two-dimensional CT images. For the 34 children undergoing chemotherapy firstly, 31 cases had surgical feasibility after chemotherapy based on the two-dimensional CT images and 3 cases could not undergo surgery because of unapparent tumor regression or tumor surrounding impor-tant vessels. However, the 34 children had surgical feasibility after chemotherapy based on the three-dimensional reconstruction results of Hisense CAS. The revision rate of surgical feasibility was 11.0%(9/82) for the 82 children. ② Based on the two-dimensional CT images, 15 cases of 82 children underwent liver left lobectomy, 21 cases underwent liver right lobectomy, 7 cases underwent mesohepatectomy, 13 cases underwent extended left hemihepatectomy, 23 cases underwent extended right hemihepatectomy, 3 cases underwent segmental hepatectomy. However, based on the three-dimensional reconstruction results of Hisense CAS, 20 cases of 82 children underwent liver left lobectomy, 29 cases underwent liver right lobectomy, 7 cases underwent mesohepatectomy, 7 cases underwent extended left hemihepatectomy, 14 cases underwent extended right hemihepatectomy, 5 cases underwent segmental hepatectomy. The revision rate of surgical scheme was 36.6%(30/82) for the 82 children. (2) Intraoperative and postoperative situations. The operation time, volume of intraoperative blood loss, duration of postoperative hospital stay of the 82 children were (182±18)minutes, 20(10)mL, (10.2±1.9)days, respectively. (3) Follow-up. All the 82 children were followed up for 10 (range, 2?18)months. There was no obvious complication occurred to the 82 children after surgery, and the residual liver can satisfy the liver compensation of body. All the children survived well.Conclusion:Three-dimensional reconstruction of Hisense CAS is conducive to judging the surgical feasibility and formulation of accurate surgical plan of children with liver tumors.

Curcuminoids are rare diketone compounds in plants and can be found in the rhizome of Curcuma longa as well as other Zingiberaceae and Araceae. Curcuminoids have been widely used in food and medical area owing to the yellow colors, as well as the antioxidant and many other pharmacological activities. Curcuminoids are a mixture of compounds containing curcumin, demethoxycurcumin and bisdemethoxycurcumin, which have distinct benzene ring substituents. Currently, curcuminoids are exclusively produced through plant extraction, which do not satisfy the meeting of the market demand. Empowered with new synthetic biology tools and metabolic engineering strategies, there is renewed interest in production of curcuminoids using microorganisms. Heterologous production of curcuminoids has been achieved using Escherichia coli, Yarrowia lipolytica, Pseudomonas putida and Aspergillus oryzae via engineering of curcuminoids biosynthesis pathway. In this review, we first describe the biological activities and various applications of curcuminoids. Next, we summarize the biosynthetic pathway of curcuminoids in Curcuma longa and discuss the catalytic mechanisms of curcumin synthases. Then, we thoroughly explore recent advances in the use of distinct microorganisms for the production of curcuminoids with a special focus on metabolic engineering strategies. Finally, we prospect the microbial production of curcuminoids by highlighting some promising techniques and approaches.
Antioxidants ; Biosynthetic Pathways/genetics* ; Curcumin ; Diarylheptanoids ; Metabolic Engineering ; Plant Extracts

Objective To study the auditory brainstem response (ABR) of normal adult CBA,C57BL,Kunming and 129 mice and analyze the ABR thresholds and latencies in order to obtain normal values and standardized testing process,thereby providing important reference for future auditory hearing research in mouse.Methods Six -week-old normal mice of CBA,C57BL,Kunming and 129(each strain containing 20 ears of 20 mice) were used in this study.ABR test with both the click and tone burst were carried on.The incidence of each wave and the thresholds and latencies of various strains of mice were recorded.Results For these four strains of mice,wave Ⅱ had the highest occurrence rate and was used to determine the thresholds.Four strains of mice all were sensitive to the sound at 8,12,16 kHz,most to 12 kHz.Under anesthesia condition,the latency of each ABR wave prolonged as testing time increase,especially the waves Ⅲ ～ V which reflected the functions of the part near the cerebral center.Conclusion Under anesthesia state,for these four strains of mice,wave Ⅱ has the highest occurrence rate and is used to determine the threshold.We determine the intensity level at which Wave Ⅱ just appeared as the ABR threshold.The stain of CBA mice is the best one to establish an animal model related to hearing function research because ABR of the other three strains are not stable as the CBA mice.Wave SP can reflect the hair cell functions indirectly.