D-psicose 3-epimerase (DPEase) is demonstrated to be useful in the bioproduction of D-psicose, a rare hexose sugar, from D-fructose, found plenty in nature. Clostridium cellulolyticum H10 has recently been identified as a DPEase that can epimerize D-fructose to yield D-psicose with a much higher conversion rate when compared with the conventionally used DTEase. In this study, the crystal structure of the C. cellulolyticum DPEase was determined. The enzyme assembles into a tetramer and each subunit shows a (β/α)(8) TIM barrel fold with a Mn(2+) metal ion in the active site. Additional crystal structures of the enzyme in complex with substrates/products (D-psicose, D-fructose, D-tagatose and D-sorbose) were also determined. From the complex structures of C. cellulolyticum DPEase with D-psicose and D-fructose, the enzyme has much more interactions with D-psicose than D-fructose by forming more hydrogen bonds between the substrate and the active site residues. Accordingly, based on these ketohexose-bound complex structures, a C3-O3 proton-exchange mechanism for the conversion between D-psicose and D-fructose is proposed here. These results provide a clear idea for the deprotonation/protonation roles of E150 and E244 in catalysis.
Binding Sites ; Biocatalysis ; Catalytic Domain ; Clostridium cellulolyticum ; enzymology ; Hexoses ; chemistry ; Manganese ; chemistry ; Protein Structure, Quaternary ; Racemases and Epimerases ; chemistry ; metabolism ; Substrate Specificity

OBJECTIVE To understand the polypharmacy burden and influencing factors of elderly tuberculosis （TB） in Guizhou province， and to provide reference for reducing the polypharmacy burden of patients. METHODS From April to July 2022， 405 elderly TB outpatients were selected from three designated TB hospitals in Guiyang City， Bijie City， and Qiandongnan Miao and Dong Autonomous Prefecture of Guizhou Province by convenience sampling method as investigation objects. The general situation questionnaire and the Living with Medicines Questionnaire （LMQ） were used for face-to-face survey. Descriptive analysis， one-way ANOVA and multivariate linear regression analysis were used to understand the score of polypharmacy burden of elderly TB patients and explore the factors effecting polypharmacy burden in TB patients. RESULTS The total polypharmacy burden score of 405 elderly TB patients was （112.65±14.59） points， which was higher than the threshold （110 points） for high burden standard in LMQ. Multivariate linear regression analysis showed that aged 80 to 92 years， self-financed+medical insurance， retreatment， drug resistance， and adverse drug reactions were the risk factors for polypharmacy burden in elderly TB patients （P＜0.05）； living in the city， family member management， volunteer management and intelligent tool-assisted management were the protective factors （P＜0.05）. CONCLUSIONS The burden of polypharmacy in elderly TB patients from Guizhou province is heavy， and is influenced by patient’s age， residence， payment method， treatment classification， drug resistance， adverse drug reactions， and medication management. It is recommended that medical staff should provide key populations with medication guidance based on influential factor for polypharmacy burden so as to reduce their polypharmacy burden.

OBJECTIVE To provid e reference and sugge stions for improving the volume-based procurement of drugs and medical consumables （hereinafter referred to as “consumables”）in China. METHODS The relevant policy documents of centralized volume-based procurement of drugs and consumables published from November 2018 to November 2021 were retrieved ； the implementation status and problems of centralized volume-based procurement of drugs and consumables in China were analyzed by using the policy analysis method and referring to relevant research literatures. RESULTS & CONCLUSIONS National health department and healthcare security administration guaranted the rational use of selected products in medical institutions through incentive and supervision measures ；healthcare security administration should optimize the way of medical insurance payment ， promote the medical institutions to control the fees by themselves ，and conduct the credit evaluation of bidding and procurement ； medical products administration should evaluate the consistency of drugs and supervise the quality of selected products. With the normalization of centralized volume-based procurement of drugs and consumables organized by the state and trans-regional alliance ， the drug varieties and dosage forms included in centralized procurement were increasingly in line with the demand of Chinese pharmaceutical market. The price of most selected drugs decreased by more than 50％，and the decrease of consumables was significantly higher than that of drugs. The selected enterprises were mainly domestic generic drug enterprises ，and domestic consumables had gradually become the competitors and substitute of imported consumables. However ，there were still some problems such as repeated bidding and procurement in various alliances and provinces （autonomous regions and municipalities ）， unclear construction of compensation mechanism in medical institutions ，inconsistent bidding and procurement rules and quality evaluation standards for consumables ，low localization rate of some consumables ，low innovation level and profitability of pharmaceutical enterprises and consumables manufacturers. Local centralized volume-based procurement should be encouraged ，and the bidding and procurement rules and quality evaluation standards of “one product ，one policy ”should be gradually established. Great importance should be paid to the construction of compensation mechanism of medical institutions ，standardize zhangqiuyu739632@126.com the dynamic adjustment of medical serv ice prices ；pharma- ceutical enterprises and consumables manufacturers should increase research and development investment to transform into innovative and diversified enterprises ，so as to improve the competitiveness of domestic drugs and consumables.

Fragile X syndrome(FXS)is caused by abnormal duplication and amplification of the FMR1 gene CGG.This article reports a pair of brothers diagnosed with FXS by genetic testing.Two patients,aged 15 and 14 years old respectively,both had clinical manifestations such as language disorders,intellectual disabilities,attention deficit disorder,autism spectrum disorder,and FXS's characteristic facial features.The proband had a rare late-onset epileptic seizure,which was well treated with levetiracetam,while his younger brother had no electroencephalogram abnormalities after repeated follow-up.This pair of cases suggests that the clinical phenotype of FXS has diversity and heterogeneity.