OBJECTIVE To optimize the management model of drugs used in investigator-initiated trial （IIT）. METHODS With benchmarking analysis， based on the practical work experience of a tertiary specialized hospital in the field of IIT drug management in Shanghai， a thorough review was conducted， involving relevant laws， regulations， and academic literature to establish benchmark criteria and the evaluation standards. Starting from the initiation of IIT projects， a detailed comparative analysis of key processes was carried out， such as the receipt， storage， distribution， use and recycling of drugs for trial. The deficiencies in the current management of IIT drugs were reviewed in detail and a series of optimization suggestions were put forward. RESULTS It was found that the authorized records of drug management were missing， the training before project implementation was insufficient， and the records of receipt and acceptance of IIT drugs were incomplete. In light of these existing problems， improvement measures were put forward， including strengthening the training of drug administrators and stipulating that only drug administrators with pharmacist qualifications be eligible to inspect and accept drugs， etc. The related systems were improved， and 17 key points of quality control for the management of IIT drugs were developed. CONCLUSIONS A preliminary IIT drug management system for medical institutions has been established， which helps to improve the institutional X2023076） framework of medical institutions in this field.

Objective To investigate the mechanism and protective effect of Humanin(HN)on rotenone(Rot)-induced toxic damage for dopamine neurons.Methods The Rot-poisened PC12 cell model was constructed,and the control group,the Rot poisening group,the HN pretreated Rot poisening group,and the HN treatment group were set up.ELISA was used to detect the content of HN inside and outside of Rot-infected cells,CCK-8 assay was used to detect cell viability,and ATP detection kit was used to detect the intracellular ATP content.Dichloro-dihydro-fluorescein diacetate(DCFH-DA)assay was used to detect the level of reactive oxygen species(ROS)in cells.Western blotting was performed to detect the expression level of mitochondrial autophagy regulatory proteins Pink1,Parkin,p62,LC3,mitochondrial biogenesis regulatory protein PGC1α,division/fusion regulatory proteins OPA1,MFN2,DRP1,p-DRP1 and antioxidant stress regulatory proteins Keap1 and Nrf2.HBAD-mcherry-EGFP-LC3 adenovirus transfected cells was used to observed the number of autophagosomes and autophagolysosomes.Results The results showed that the intracellular concentration of HN in PC12 in the Rot poisening group was significantly higher than that in the control group(P＜0.05);Compared with the control group,the Rot poisening group had significantly decreased activity of PC12 cells,decreased ATP content and increased production of ROS.After the poisen of Rot in PC12 cells,the expression of Pink1 and p-Parkin,the ratio of LC3Ⅱ/LC3Ⅰ and the expression of p-DRP1 in mitochondrial fusion protein was increased,while the expression of p62,the expression of mitochondrial biogenesis protein PGC1 α,mitochondrial fusion proteins MFN2 and OPA1,and antioxidant stress proteins Keap1 and Nrf2 were decreased(all P＜0.05).The number of autophagosomes and autophagolysosomes in PC12 cells in the Rot poisening group was higher than that in the control group(P＜0.05),and HN pretreatment(20 μmol/L)could significantly improve the changes mentioned above caused by Rot poisening(P＜0.05).Conclusion HN ameliorates Rot-induced toxic damage for dopamine neurons by inhibiting mitophagy and mitochondrial division and promoting mitochondrial biogenesis and fusion,and anti-oxidative stress.

【Objective】 To explore the distribution of serological markers related to samples whose serological test results were inconsistent with HBV DNA test results among voluntary blood donors in Xi′an. 【Methods】 A total of 71 HBsAg ELISA positive and NAT non-reactive (ELISA+ /NAT-)blood samples were collected from Shaanxi Blood Center from November 1, 2022 to April 30, 2023. The serological markers of hepatitis B were detected by electrochemiluminescence method, and the HBV S region and C region gene fragments were amplified by nested-PCR. 【Results】 The positive rate of nested-PCR in double ELISA+ /NAT- group(n=30) was statistically higher than that of ELISA+ /NAT- group(n=41)(60% vs 24.4%, P<0.05). Donors in double ELISA+ /NAT- group were all first-time blood donors, with the positive rate of anti-HBc in serum of 100%, and the serological pattern was mainly positive for items 1, 4 and 5 items(80%). Among the ELISA+ /NAT- group, 31.7% were repeat blood donors, with the positive rate of anti-HBc in serum of only 19.51%, and the serological patterns were mainly single anti-HBs positive (43.90%) and all negative (36.58%). 【Conclusion】 There are false positives in the test results of ELISA+ /NAT- group, which leads to unnecessary blood discarding. Meanwhile, the samples with negative NAT may have low levels of HBV DNA, which may lead to missed detection. It is suggested that multiple systems and methods should be applied to trace the blood donors who are HBsAg positive and NAT non-reactive, so as to improve the accuracy of HBV screening of blood donors and reduce blood waste.

Objective To compare the pharmacokinetics of crushed posaconazole enteric-coated tablets and oral suspension after intragastric administration in rabbits.Methods The experiment was designed in a randomized cross-over study.Six New Zealand rabbits were intragastrically administrated with crushed posaconazole enteric-coated tablets or suspension,and blood was collected at specific time points.The concentration of posaconazole in plasma was determined by high-performance liquid chromatography,and the pharmacokinetic parameters of both groups were calculated with DAS 2.0 software.Results The main pharmacokinetic parameters of posaconazole enteric-coated tablets and suspension were obtained as follows:AUC0-twere(40.03±5.04)and(49.92±16.09)μg·mL-1·h;AUC0-∞ were(44.00±4.50)and(51.10±16.80)μg·mL-1·h;t1/2 were(7.30±1.13)and(8.53±1.34)h;Cmrx were(3.12±0.57)and(2.78±0.60)μg·mL-1;apparent volume of distribution(Vd)were(2.40±0.34)and(2.59±0.76)L·kg-1;clearance rate(CL)were(0.23±0.02)and(0.22±0.08)L·h-1·kg.There were no statistic differences in AUC0-t,Cmax and Vd between posaconazole suspension and crushed enteric-coated tablets after intragastric administration(all P＞0.05).Conclusion There was no pharmacokinetic advantage for crushed enteric-coated tablets against oral suspension.

Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking. Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns. Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023-1.954;P = 0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains. Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.

Objective To investigate the effectiveness and safety of a new nerve block puncture needle for nerve block in patients undergoing total knee arthroplasty (TKA). Methods A total of 106 patients undergoing TKA were enrolled, and randomly divided into conventional group (n=53) and study group (n=53). Conventional nerve block puncture needle was used in the conventional group, and a new nerve block puncture needle was used in the study group. The needle insertion effects, block effects, pain [Visual Analogue Scale (VAS)], stress responses [heart rate (HR) and mean arterial pressure (MAP)] and safety were observed in both groups. Results The number of needle insertions, corrections and the duration of needle insertion were significantly lower or shorter in the study group compared with the conventional group (P < 0.05). The success rate of one-time puncture in the study group was 81.13%, which was significantly higher than 62.26% in the conventional group (P < 0.05). There were no statistically significant differences in the onset time, duration and success rate of block between the two groups (P>0.05). During needle insertion, the HR, MAP and VAS scores were significantly lower in the study group compared with the conventional group (P < 0.05). The overall incidence of adverse events related to nerve blockade was significantly lower in the study group than that in the conventional group (P < 0.05). Conclusion The application of the novel nerve block needle in patients undergoing TKA exhibits good effects and high effectiveness, which can reduce stress responses and the risk of adverse events related to needle insertion.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

Objective:Based on the relevance risk analysis of medical equipment,to formulate process management strategies to improve the clinical operation efficiency of medical equipment.Methods:The risk matrix was evaluated from the perspectives of subject,quality,environment,system and diagnosis and treatment perspective,the comprehensive evaluation model of relevance risk was established,and multiple process management countermeasures were formulated.400 sets of medical equipment in clinical use in Shanghai Eighth People's Hospital from April 2021 to March 2022 were selected and divided into the control group and the observation group by the digital table method,with 200 sets in each group.The control group adopted the individualized risk analysis method for process management,and the observation group adopted the relevance risk analysis method for process management.The risk level and operation benefits of the two groups of medical equipment were compared and analyzed.Results:The high risk rates of medical imaging diagnostic and auxiliary equipment,surgical treatment equipment,life support and first aid equipment,extracorporeal circulation and blood processing equipment,health monitoring and rehabilitation equipment in the observation group were 17.39%(4/23),14.58%(7/28),12.24%(6/49),5.55%(1/18)and5.06%(5/62),respectively,which were lower than those in the control group,the difference was statistically significant(x2=4.132,4.009,6.275,4.833,4.859,P<0.05).The scores of cost benefit,social benefit,diagnosis and treatment benefit and development benefit of medical equipment in the observation group were(91.37±6.15)points,(92.78±3.80)points,(95.25±2.09)points and(90.51±3.82)points,respectively,which were higher than those in the control group,the difference was statistically significant(t=2.392,3.877,4.841,2.504,P<0.05).Conclusion:The relevance risk analysis method can reduce the probability and hazard degree of medical equipment safety risks,improve the clinical operation efficiency of medical equipment,and the process management strategy is in line with the actual needs of the medical equipment lifecycle management.

Objective:To investigate the characteristics of neointimal hyperplasia (NIH) in patients with in-stent restenosis (ISR) over 5 years post-drug-eluting stent (DES) implantation based on optical coherence tomography (OCT).Methods:In this cross-sectional study, patients with DES-ISR who underwent OCT examination at PLA General Hospital between March 2010 and March 2022 were retrospectively included. All patients were divided into≤5 years DES-ISR group and>5 years DES-ISR group according to the time interval after DES implantation. Quantitative and qualitative analyses were conducted on OCT images to compare the clinical data and lesion characteristics of two patient groups. Furthermore, the independent clinical predictive factors of in-stent neoatherosclerosis (ISNA) were analyzed by multivariable logistic regression.Results:A total of 230 DES-ISR patients with 249 lesions were included, with an age of (63.1±10.4) years and 188 males (81.7%). The median interval after DES implantation was 6 (2, 9) years. There were 117 patients (122 ISR lesions) in the≤5 years DES-ISR group, and 113 patients (127 ISR lesions) in the>5 years DES-ISR group. Compared with≤5 years DES-ISR,>5 years DES-ISR showed more heterogeneous patterns (65.4% (83/127) vs. 48.4% (59/122), P=0.007), diffuse patterns (46.5% (59/127) vs. 31.2% (38/122), P=0.013), macrophage accumulations (44.1% (56/127) vs. 31.2% (38/122), P=0.035) in NIH and higher prevalence of ISNA (83.5% (106/127) vs. 72.1% (88/122), P=0.031). According to multivariable logistic regression, the independent predictive factor for ISNA was female ( OR=0.44, 95% CI 0.21-0.90, P=0.026). Female ( OR=0.48, 95% CI 0.23-0.99, P=0.046) and low-density lipoprotein cholesterol level ( OR=1.62, 95% CI 1.01-2.59, P=0.046) were independent predictive factors, respectively, for lipid ISNA. Calcified ISNA was independently associated with time interval of post-DES implantation ( OR=1.18, 95% CI 1.07-1.29, P=0.001). Conclusion:DES-ISR patients with a time interval of>5 years after stent implantation have a higher prevalence of ISNA and more complex lesions. Gender, the level of low-density lipoprotein cholesterol, and the time interval post-DES implantation are independently correlated with ISNA, lipid ISNA, and calcified ISNA.

Nanozymes, a groundbreaking discovery by Chinese scientists, represent a novel and remarkable property of nanomaterials. They not only exhibit catalytic activity comparable to natural enzymes, but also boast exceptional stability, tunable reactivity, and the ability to catalyze reactions under mild conditions. The identification of nanozymes has unveiled the biocatalytic potential of inorganic nanomaterials. In parallel, inorganic minerals have long been regarded as pivotal catalysts in the origin of life, driving the synthesis of early biomolecules. These minerals not only facilitate redox reactions that convert simple inorganic compounds into organic molecules but also enable chiral selection, the synthesis of biomacromolecules, and radioprotective functions via their surface structures. Recent advances suggest that inorganic nanomaterials can delicately catalyze the formation of biomolecules, aid in macromolecular assembly, and provide radiation shielding. Furthermore, nanominerals are found in abundance across Earth and extraterrestrial environments. This paper seeks to explore the potential of nanozymes as catalytic agents in the processes that gave rise to life, integrating the catalytic roles of inorganic minerals with the unique attributes of nanozymes, which will provide a new perspective for research of origin of life.