Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

OBJECTIVE To evaluate the consistency between the quetiapine LC-MS/MS kit and the laboratory-built method(reference method) in the detection results of quetiapine therapeutic drug monitoring. METHODS A total of 120 remaining plasma samples were collected from patients receiving quetiapine therapeutic drug monitoring from March to October in 2021. The plasma concentration of quetiapine was detected by kit and reference method respectively. The analysis of correlations and consistency was performed by outlier analysis, linear regression and Bland-Altman method. RESULTS No outliers were detected. The linear regression equation was Y=1.018X+4.400(r=0.998), indicating a good correlation. The Bland-Altman plot analysis showed good agreement between the two measurements. CONCLUSION The detection results of quetiapine LC-MS/MS kit and reference method are in good agreement. The kit can be used for clinical quetiapine treatment drug monitoring.

Objective:To analyze the effect of recombinant human thrombopoietin(rhTPO)on platelet(PLT)reconstitution after autologous peripheral blood stem cell transplantation(APBSCT)in patients with multiple myeloma(MM).Methods:The clinical data of 147 MM patients who were diagnosed in the First Affiliated Hospital of Soochow University and received APBSCT as the first-line therapy were retrospectively analyzed.According to whether rhTPO was used during APBSCT,the patients were divided into rhTPO group(80 cases)and control group(67 cases).The time of PLT engraftment,blood product infusion requirements,the proportion of patients with PLT recovery to ≥ 50 × 109/L and ≥ 100 × 109/L at+14 days and+100 days after transplantation,and adverse reactions including the incidence of bleeding were compared between the two groups.Results:There were no significant differences between the two groups in sex,age,M protein type,PLT count at the initial diagnosis,median duration of induction therapy before APBSCT,and number of CD34+cells reinfused(all P＞0.05).The median time of PLT engraftment in the rhTPO group was 10(6-14)days,which was shorter than 11(8-23)days in the control group(P＜0.001).The median PLT transfusion requirement in the rhTPO group during APBSCT was 15(0-50)U,which was less than 20(0-80)U in the control group(P=0.001).At+14 days after transplantation,the proportions of patients with PLT 2 50 × 109/L in the rhTPO group and the control group were 66.3％and 52.2％,while the proportions of patients with PLT ≥ 100 × 109/L were 23.8％and 11.9％,respectively,with no significant differences(all P＞0.05).At+100 days after transplantation,the proportion of patients with PLT ≥ 50 × 109/L in rhTPO group and control group was 96.3％and 89.6％,respectively(P＞0.05),but the proportion of patients with PLT ≥ 100 × 109/L in rhTPO group was higher than that in control group(75.0％vs 55.2％,P=0.012).There was no difference in the overall incidence of bleeding events in different locations during period of low PLT level of patients between the two groups.In rhTPO group,the rhTPO administration was well tolerated,and the incidences of abnormal liver and kidney function and infection were similar to those in the control group.Conclusion:When MM patients undergo first-line APBSCT,subcutaneous injection of rhTPO can shorten the time of platelet engraftment,reduce the transfusion volume of blood products,and be well tolerated,moreover,more patients have achieve a high level of PLT recovery after transplantation,which is very important for ensuring the safety of APBSCT and maintenance therapy.

Objective:To design a method to introduce random six-dimensional setup error (6D-SE) into the intensity-modulated radiotherapy (IMRT) planning for rectal cancer and evaluate its dosimetric effect.Methods:A total of 21 IMRT plans for patients with rectal cancer were randomly selected as reference plans [2 Gy per fraction for a total of 50 Gy; a 5 mm uniform margin around the clinical target volume (CTV) was taken as the planning target volume (PTV)]. For each fraction of the reference plan, a randomly generated 6D-SE was introduced by adjusting the geometrical parameters of the radiation field, and the dose was recalculated. The overall dose distribution with 6D-SE was obtained by adding up the dose of each fraction. A treatment simulation program that could complete the above workflow was developed using the Varian Eclipse scripting API (ESAPI). 6D-SEs that obey two preset distributions [distribution 1: translational error obey N(0, 4 2), and rotational error obey N(0, 2 2); distribution 2: translational error obey N(0, 2 2), and rotational error obey N(0, 1 2)] were introduced into the reference plans, and the dosimetric effects were assessed. Results:When the reference plans, error distribution 1, and error distribution 2 were applied, the Dmin values of the CTV were (49.4±0.41), (47.56±0.76), and (49.17±0.64) Gy, respectively; the D98% values of the CTV were (50.23±0.07), (49.98±0.10), and (50.27±0.09) Gy, respectively; the D98% values of the primary target area (the kernel part of the target area, excluding the margins) were (50.25±0.08), (50.42±0.13), and (50.33±0.10) Gy, respectively; the D98% values of the marginal area were (50.22±0.10), (49.88±0.11), and (50.26±0.10) Gy, respectively. In addition, compared with the result of the reference plans, the result of errors 1 and 2 showed no significant changes in the mean dose of the bladder and femoral heads ( P>0.05), despite slight decreases in the conformity index of the dose distribution with limited clinical significance. Conclusion:The proposed method and the treatment simulation program developed thereupon can introduce the 6D-SE obeying different distributions into the IMRT plans for rectal cancer on demand and provide overall dosimetric changes.

Humans ; Multiple Myeloma/genetics* ; Neoplasm, Residual/diagnosis* ; Flow Cytometry ; High-Throughput Nucleotide Sequencing

OBJECTIVE To explore the current status and challenges of informatization construction for clinical trial centralized pharmacy based on the relevant experience of The First Affiliated Hospital, Zhejiang University School of Medicine. METHODS Review the development of clinical trial drug management and informatization process, along with the management experience of the hospital where the author works, and then introduce the framework and specific operation details of the informatization system when conducting centralized management method, summarize the problems encountered at present and propose future prospects. RESULTS Informatization construction played a significant role in the management of central pharmacies in clinical trial, enabling them to adapt to the complex management needs of investigational products and meet the high standards and strict requirements of Good Clinical Practice(GCP) and related regulations. However, the development of the current information system was still not perfect, and there were problems that need to be solved. CONCLUSION Each hospital needs to pay attention to the informatization construction of the central pharmacy of the clinical trial, improve and perfect the centralized management method of the investigational products, and explore modern technologies and equipments, which are of immense importance for the construction of the clinical trial pharmacy management that conforms to the development trend of drug clinical trials and GCP.

Organoid models are used to study kidney physiology, such as the assessment of nephrotoxicity and underlying disease processes. Personalized human pluripotent stem cell-derived kidney organoids are ideal models for compound toxicity studies, but there is a need to accelerate basic and translational research in the field. Here, we developed an automated continuous imaging setup with the "read-on-ski" law of control to maximize temporal resolution with minimum culture plate vibration. High-accuracy performance was achieved: organoid screening and imaging were performed at a spatial resolution of 1.1 μm for the entire multi-well plate under 3 min. We used the in-house developed multi-well spinning device and cisplatin-induced nephrotoxicity model to evaluate the toxicity in kidney organoids using this system. The acquired images were processed via machine learning-based classification and segmentation algorithms, and the toxicity in kidney organoids was determined with 95% accuracy. The results obtained by the automated "read-on-ski" imaging device, combined with label-free and non-invasive algorithms for detection, were verified using conventional biological procedures. Taking advantage of the close-to-in vivo-kidney organoid model, this new development opens the door for further application of scaled-up screening using organoids in basic research and drug discovery.
Humans ; Kidney ; Organoids ; Pluripotent Stem Cells

Objective To investigate the risk factors for acute variceal bleeding (AVB) in acute-on-chronic liver failure (ACLF) and its influence on prognosis. Methods A total of 1409 ACLF patients who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from 2009 to 2015 were followed up for 6 months, and according to the presence or absence of AVB, they were divided into AVB group and non-AVB group. The Student's t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier curves were plotted and the Log-rank test was performed to analyze mortality rate and progression during follow-up, and a binary Logistic regression analysis was used to investigate the risk factors for AVB. Results Among these 1409 patients, 167 (11.85%) experienced AVB. The 30-day survival rate was 43.42% in the AVB group and 67.79% in the non-AVB group ( χ 2 =33.558, P < 0.001), and the 180-day survival rate was 18.91% in the AVB group and 53.97% in the non-AVB group ( χ 2 =76.881, P < 0.001). The Log-rank test showed significant differences in 30- and 180-day survival rates between the AVB group and the non-AVB group ( χ 2 =40.950 and 89.320, both P < 0.05). The Logistic regression analysis showed that pleural effusion (odds ratio [ OR ]=1.522, 95% confidence interval [ CI ]: 1.071-2.162, P =0.019), acute kidney injury (AKI) ( OR =2.201, 95% CI : 1.415-3.426, P < 0.001), ABC subtype of ACLF ( OR =2.491, 95% CI : 1.489-4.168, P =0.001), ACLF stage ( OR =2.403, 95% CI : 1.687-3.421, P < 0.001), and urea( OR =2.567, 95% CI : 1.570-4.196, P < 0.001)were independently associated with AVB in ACLF patients. Conclusion AVB is an important influencing factor for the short-term survival of ACLF patients, and pleural effusion, AKI, BC subtype of ACLF, advanced ACLF, and urea are independent risk factors for the onset of AVB.

Alzheimer Disease/genetics* ; Animals ; Apolipoprotein E4/metabolism* ; Gene-Environment Interaction ; Hippocampus/metabolism* ; Male ; Noise/adverse effects* ; Rats