OBJECTIVE To build a new workflow of pharmacy intravenous admixture services （PIVAS）， effectively connect intelligent equipment， and promote the intelligent development of PIVAS. METHODS Based on intelligent auxiliary equipment， PIVAS workflow was optimized， and a process-oriented model was established. This model integrated intelligent prescription review （automatic prescription review+manual intervention mode）， intelligent labeling， intelligent allocation， intelligent sorting， and finished infusion quality inspection system. Furthermore， an assessment was conducted to examine unreasonable medical order rate of intelligent prescription review， the working efficiency and error rate of intelligent labeling machine and intelligent sorting machine， and the dispensing efficiency and accuracy of intelligent dispensing robot. RESULTS Under the intelligent prescription review mode， the rate of unreasonable medical orders decreased from 0.157% to 0.050% （P＜0.05）； automatic labeling efficiency reached 21.7 sheets/min， surpassing the manual labeling efficiency of 13.8 sheets/min （P＜0.05）， and the daily labeling error rate decreased from 6.1‰ to 2.5‰ （P＜0.05）. Simultaneously operating two dispensing robots significantly improved the efficiency of batch dispensing and reduced the residual amount of liquid medicine （P＜0.05）； additionally， a quality testing system for finished infusion was established， involving appearance， Tyndall effect， insoluble particles， turbidity， absorbance， pH and osmotic pressure， to ensure the quality of finished infusion and reduce the risk of infusion. CONCLUSIONS The new process of PIVAS connected with intelligent devices in our hospital can improve work efficiency， reduce dispensing errors， ensure the quality of finished infusion， and improve the level of pharmaceutical care.

OBJECTIVE To construct a prediction model for tacrolimus trough concentration based on population pharmacokinetics （PPK） information and machine learning， evaluate its predictive performance in clinical therapeutic drug monitoring （TDM） data， and provide evidence-based support for individualized dose adjustment of tacrolimus after renal transplantation. METHODS A retrospective cohort study design was adopted， and consecutive TDM records of kidney transplant recipients treated in the First Affiliated Hospital of University of Science and Technology of China （Anhui Provincial Hospital） from January to June 2025 were included to construct the final analysis set. Based on 29 input variables including previous TDM concentration， previous concentration/dose （ C / D ） ratio， and individual predicted exposure （IPRE）， 13 commonly used regression algorithm models and 1 weighted ensemble model were systematically compared. The dataset was split into training set and test set in an 80∶20 ratio by patient. Five-fold cross-validation based on patient grouping was performed on the training set， and the model performance was evaluated on the obtained evaluation points using the coefficient of determination （ R 2 ）， mean absolute error （MAE）， root mean square error （RMSE）， Pearson correlation coefficient （Corr） and ±20%/±30% accuracy. The SHapley Additive exPlanations （SHAP） method was used for model interpretability analysis to identify core predictive features. RESULTS A total of 809 consecutive TDM records from 83 kidney transplant recipients were included， with 66 cases in the training set and 17 cases in the test set. The SVR model showed the best performance， with R 2 of 0.649 8， MAE of 1.126 0 ng/mL， RMSE of 1.478 6 ng/mL， Corr of 0.819 1， ±20% accuracy of 59.68%， and ±30% accuracy of 79.03%. The Weighted Ensemble model and Extra Trees model ranked second and third， respectively. SHAP interpretability analysis showed that the top 6 features contributing to the prediction were IPRE， previous TDM concentration， previous C/D ratio， dose-normalized concentration， hematocrit （HCT）， and concentration-dose coefficient （ θ cd ）， among which IPRE was the core predictive feature （SHAP mean value 0.915 4）. CONCLUSIONS The machine learning model incorporating PPK information demonstrates good predictive ability for tacrolimus concentration in the current TDM cohort. SVR is the optimal model， IPRE is the core predictive feature of the model， and a few core PK-derived features （IPRE， dose-normalized concentration， θ cd ） together with clinical features （previous TDM concentration， HCT， etc.） constitute the main information sources for model prediction.

Metastasis is the leading cause of death from cutaneous melanoma. Identifying metastasis-related targets and developing corresponding therapeutic strategies are major areas of focus. While functional genomics strategies provide powerful tools for target discovery, investigations at the protein level can directly decode the bioactive epitopes on functional proteins. Aptamers present a promising avenue as they can explore membrane proteomes and have the potential to interfere with cell function. Herein, we developed a target and epitope discovery platform, termed functional aptamer evolution-enabled target identification (FAETI), by integrating affinity aptamer acquisition with phenotype screening and target protein identification. Utilizing the aptamer XH3C, which was screened for its migration-inhibitory function, we identified the Chondroitin Sulfate Proteoglycan 4 (CSPG4), as a potential target involved in melanoma migration. Further evidence demonstrated that XH3C induces cytoskeletal rearrangement by blocking the interaction between the bioactive epitope of CSPG4 and integrin α4. Taken together, our study demonstrates the robustness of aptamer-based molecular tools for target and epitope discovery. Additionally, XH3C is an affinity and functional molecule that selectively binds to a unique epitope on CSPG4, enabling the development of innovative therapeutic strategies.

The 5-hydroxytryptamine 2A receptor (5-HT_2AR) is one of the key targets in the development of novel antidepressants. To develop new antidepressants targeting the 5-HT_2A receptor, this study established a high-throughput screening method for drugs targeting the 5-HT_2A receptor based on the principle of detecting calcium flux signals. The immunofluorescence assay and western blotting were employed to evaluate receptor expression levels in the 5-HT_2AR-CHO cell line. The reaction system parameters, including cell seeding density, DMSO concentration, and dye incubation time, were optimized with Z'-factor and signal window values as evaluation indicators. The specificity, precision, stability, and applicability of the method were assessed. Results indicated that the 5-HT_2AR-CHO cell line stably expressed high levels of the 5-HT_2A receptor. The optimized screening method involved a reaction system with 10 000 cells/well, 0.2% DMSO, and 2 h incubation with Calcium 6 dye. The method demonstrated excellent specificity, with inter-batch precision below 10% for the detection of 5-hydroxytryptamine (5-HT) at low, medium, and high concentrations. Testing four compounds that target the 5-HT_2A receptor- agonists 2,5-dimethoxy-4-iodoamphetamine (DOI), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), and lysergic acid diethylamide (LSD), along with the antagonist MDL100907-yielded Z'-factors (at EC₈₀) greater than 0.85 and signal window values over 0.91. The EC₅₀ values of these compounds were in the nanomolar range, and their potency rank order aligned with previously reported data, confirming the reliability of the established method. When being applied to the detection of 38 known active compounds, the method efficiently identified 5-HT_2A receptor agonists and antagonists while showing no response to non-target compounds. In conclusion, this study successfully constructs a high-throughput screening approach for 5-HT_2A receptor-targeting drugs based on calcium flux signals. The method possesses strong specificity, high sensitivity, and robust stability, being suitable for screening antidepressants targeting the 5-HT_2A receptor.
High-Throughput Screening Assays/methods* ; Receptor, Serotonin, 5-HT2A/metabolism* ; Animals ; CHO Cells ; Cricetulus ; Calcium Signaling/drug effects* ; Antidepressive Agents/pharmacology* ; Humans ; Serotonin 5-HT2 Receptor Antagonists/pharmacology* ; Calcium/metabolism*

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To investigate the mosquito-borne viruses carried by mosquito specimens collected from Huachuan county and Huanan county in Heilongjiang province.Methods:Mosquito samples were collected locally in 2023 and processed in the laboratory. Homogenates of the mosquitoes were inoculated into cells for virus isolation, followed by molecular and bioinformatics analyses of the viral isolates.Results:In 2023, ten viral isolates were obtained from Anopheles sinensis specimens collected in Heilongjiang province, China. Among these isolates, one was identified as Culex flavivirus (CxFV), one as Menghai rhabdovirus (MRV), and eight as Nam Dinh virus (NDiV). The phylogenetic analysis showed that CxFV belongs to genotype I and is clustered with the strains isolated from Liaoning province in 2011 and Ningxia Hui autonomous Region in 2019 in the same evolutionary branch, with amino acid similarity ranging from 98.2% to 99.2% and nucleotide similarity ranging from 98.8% to 99.2%. The MRV strain belongs to the same evolutionary subclade as the strain detected in Guangdong, with both nucleotide and amino acid similarity of 98.0%. Eight NDiV isolates clustered with the South Korean isolates on the same evolutionary branch, forming an independent evolutionary sub-branch. The nucleotide similarity among these eight isolates ranged from 98.5% to 99.7%, while the amino acid similarity ranged from 98.1% to 99.7%. In comparison, when matched with other NDiV isolates from China, the nucleotide similarity of these eight isolates ranged from 94.1% to 97.8%, and the amino acid similarity ranged from 93.5% to 97.7%.Conclusions:This study represents the first isolation of CxFV, MRV, and NDiV in Heilongjiang province, China, and the findings provide fundamental data for the prevention and control of mosquito-borne viral diseases in this region.

Objective:To evaluate the effect of baicalein on acute myocardial injury in rats with high-level spinal cord injury (SCI) and the role of nuclear factor E2-related factor 2 (Nrf2).Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-300 g, were divided into 4 groups ( n=6 each) using a random number table method: sham operation group (Sham group), SCI group, SCI+ baicalein group (SCI+ Bai group) and SCI+ baicalein+ ML385 group (SCI+ Bai+ ML385 group). The high-level SCI rat model was established by the modified Allens method. In Sham group, the 7th cervical vertebra (C 7) was only exposed, but the spinal cord was not hit. In SCI group, C 7 was exposed and the spinal cord was hit. In SCI+ Bai group, baicalein 50 mg/kg was intraperitoneally injected immediately after SCI. In SCI+ Bai+ ML385 group, Nrf2 inhibitor ML385 30 mg/kg was intraperitoneally injected at 1 h before SCI, and baicalein 50 mg/kg was intraperitoneally injected immediately after SCI. The rats were anesthetized at 24 h after SCI and sacrificed after the blood samples from the abdominal aorta were collected and the hearts were taken for microscopic examination of the pathological changes (by HE staining) which were scored and the ultrastructure of cells (with a transmission electron microscope) and for determination of the serum cardiac troponin I (cTnI) concentrations (by enzyme-linked immunosorbent assay), content of ferrous ion (Fe 2+ ) in myocardial tissues (by colorimetry), contents of malondialdehyde(MDA) and glutathione (GSH) and activity of superoxide dismutase(SOD) in myocardial tissues (by biochemical method) and expression of glutathione peroxidase 4 (GPX4), acyl CoA synthase long chain family member 4 (ACSl4) and Nrf2 protein and mRNA in myocardial tissues (by Western blot and fluorescent quantitative polymerase chain reaction). The mitochondrial Flameng score was assessed and recorded. Results:Compared with Sham group, the pathological score, mitochondrial Flameng score and serum cTnI concentrations were significantly increased, the contents of Fe 2+ and MDA in myocardial tissues were increased, the content of GSH and SOD activity were decreased, the expression of GPX4 was down-regulated, and the expression of ACSL4 and Nrf2 was up-regulated in SCI group ( P<0.05). Compared with SCI group, the pathological score, mitochondrial Flameng score and serum cTnI concentration were significantly decreased, the contents of Fe 2+ and MDA in myocardial tissues were decreased, the contents of GSH and SOD activity were increased, the expression of GPX4 and Nrf2 was up-regulated, and the expression of ACSL4 was down-regulated in SCI+ Bai group ( P<0.05). Compared with SCI+ Bai group, the pathological score, mitochondrial Flameng score and serum cTnI concentrations were significantly increased, the contents of Fe 2+ and MDA in myocardial tissues were increased, the content of GSH and SOD activity were decreased, the expression of GPX4 and Nrf2 was down-regulated, and the expression of ACSL4 was up-regulated in SCI+ Bai+ ML385 group ( P<0.05). Conclusions:Baicalein can alleviate acute myocardial injury in rats with high-level SCI, and Nrf2 is involved in this process.

OBJECTIVE T o explore the values of body temperature,white blood cells(WBC),neutrophils(NEUT),platelets(PLT),red blood cell distribution width(RDW),procalcitonin(PCT)and C-reactive procal-citonin(PCT)in early diagnosis of postoperative nosocomial infections in the intensive care unit(ICU)patients undergoing surgical procedures.METHODS The clinical data that were collected from the surgery patients who were hospitalized in ICU of Affiliated Hospital of Nantong University from Mar.2021 to May 2022 were retro-spectively analyzed,and the enrolled patients were divided into the infection group with 45 cases and the non-infection group with 130 case according to the status of nosocomial infections.The highest body temperature and the levels of WBC,NEUT,PLT,RDW,PCT and CRP were observed and compared between the infection group within 48 hours before diagnosis with nosocomial infections and the non-infection group after ICU stay for 48 hours.The values of the single and joint detection of the indexes in prediction of postoperative nosocomial infec-tions in the ICU patients were analyzed.RESULTS The body temperature,WBC,NEUT,RDW,PCT and CRP of the infection group were 38.30(37.80,38.80)℃,14.10(10.90,17.30)× 109/L,12.22(9.32,15.12)×109/L,14.10(12.70,15.50)％,1.20(0.10,2.30)ng/ml and 55.00(40.00,70.00)mg/L,respectively,high er than those of the non-infection group(P＜0.05).CRP,body temperature,PCT,NEUT and WBC showed remarkable diag-nostic effects;the area under the curves(AUCs)of the above indexes were 0.968,0.952,0.939,0.896 and 0.886,respectively.The sensitivity of the joint detection of PCT and CRP was 0.978,with the specificity 0.985 and AUC 0.980;the sensitivity of the joint detection of body temperature,PCT and CRP was 0.978,with the specificity 0.992,AUC 0.991.CONCLUSIONS The ICU patients with postoperative nosocomial infections show high levels of body temperature,WBC,NEUT,PCT and CRP.The body temperature,PCT and CRP have high sensitivity and specificity,showing certain values in prediction of postoperative nosocomial infection in the ICU pa-tients;the joint detection of the indexes has higher diagnostic efficiency.

Objective To investigate the impact of lower inspiratory peak flow rates on airway peak pressure when using a ventilator to maintain respiratory function during the advanced life support phase of in-hospital cardiopulmonary resuscitation(CPR).Methods A prospective study was conducted,30 patients who underwent CPR for more than 20 minutes admitted to Lishui Municipal Central Hospital between September 2021 and December 2023 were enrolled as the study subjects.Volume controlled ventilation(VCV)with a descending flow waveform was used,while other preset parameters remained unchanged.Airway peak pressure was measured at different peak flow rates(55,50,45,and 40 L/min).The influence of varying flow rates on peak pressure was analyzed.Results During CPR,patients were in a continuous state of chest compressions.When the ventilator parameters were set conventionally,alarms for high airway pressure,low tidal volume(VT),and high respiratory rate often occurred,which affected the effectiveness of ventilatory support.There was a significant variation in airway peak pressure among different patients.As the peak flow rate increased from 40 L/min to 55 L/min,the airway peak pressure gradually increased.During the process of reducing the peak flow rate,the pulse oxygen saturation(SpO2)of all patients remained stable without significant changes.The 40 L/min group had significantly lower peak pressures than the 50 and 55 L/min groups,whereas the 55 L/min group had significantly higher pressures than all others[cmH2O(1 cmH2O≈0.098 kPa):41.20±9.06 vs.47.90±9.04 and 53.70±7.96,all P<0.05].When comparing patients with peak flow rates of 40 L/min and 50 L/min,as well as 45 L/min and 55 L/min,the average airway peak pressure increased significantly with each 10 L/min increment in inspiratory peak flow rate.However,the SpO2 remained essentially unchanged or slightly increased as the peak flow rate decreased.There were no statistically significant differences in SpO2 among patients at different peak flow rate levels.When the peak flow rate was set at 55,50,45,and 40 L/min,the proportions of patients with airway peak pressure>40 cmH2O were 100.0%,83.3%,63.3%,and 53.3%,respectively.Among them,the proportions of patients with airway peak pressure>50 cmH2O were 66.7%,40.0%,16.6%,and 16.6%,respectively.As the peak flow rate decreased,the proportion of patients with airway peak pressure>40 cmH2O gradually decreased.If the peak flow rate was set at 45 L/min or lower,the number of patients with airway peak pressure>50 cmH2O during CPR was less than 50.0%of the total number of cases.Conclusions During mechanical ventilation in CPR,using volume-controlled ventilation(VCV)mode with a decelerating waveform,improper peak flow rate settings can easily trigger high airway pressure alarms and result in low tidal volume(VT),leading to poor synchrony between the ventilator and the patient.Compared to peak flow rates of 55 L/min and above,selecting an inspiratory peak flow rate of 40 L/min and setting the high-pressure alarm at 50 cmH2O is suitable for the mechanical ventilation needs of most patients and does not affect oxygenation levels.This is a more appropriate choice.

ObjectiveTo analyze the genomic characteristics of Streptococcus pyogenes (GAS) isolated from children with respiratory tract infections in a tertiary hospital in Jinshan District of Shanghai during 2013‒2024, to compare the changes in trend for genomic characteristics before and after 2000, and to provide scientific data for the prevention and control of GAS infections. MethodsGAS strains isolated from children with respiratory tract infections in this hospital were collected from 2013 to 2024. Antimicrobial susceptibility of the isolated strains to 12 antibiotics, including penicillin, cefotaxime, cefepime, linezolid, vancomycin, meropenem, chloramphenicol, ofloxacin, levofloxacin, erythromycin, clindamycin, and tetracycline, was determined using broth microdilution plate method. Besides, whole genome sequencing (WGS) was used to analyze multilocus sequence type (MLST), emm typing, carriage of superantigen genes, mobile genetic element (MGE), carriage of virulence gene, and genomic phylogenetic tree of the isolated strains. ResultsA total of 50 GAS strains were collected and identified from children with respiratory tract infections aged 4‒14 years old, and the resistance rates of those isolates to erythromycin, clindamycin, and tetracycline were 100.00%, 100.00%, and 86.00%, respectively. There were two emm types in the GAS isolates; the emm12 type accounted for 76.00% (38/50), corresponding to ST36 type, and the emm1 type accounted for 24.00% (12/50), corresponding to ST28, ST1274, and new-1 types. There was a statistically significant difference in the constitution of the MLST before and after 2020 (P=0.015). All the isolates carried the superantigen genes speC, speG, ssa, and smeZ. The predominant emm12 isolates belonged to the Clade Ⅱ, carrying the mobile elements ICE-emm12 (harboring erythromycin-resistance gene ermB and tetracycline-resistance gene tetM) and ΦHKU.vir (carrying virulence genes speC and ssa). The emm1 isolates carried the mobile elements ICE-HKU488 (harboring erythromycin-resistance gene ermB and tetracycline-resistance gene tetM) and ΦHKU488.vir (carrying virulence genes speC and ssa), and had close phylogenetical relationships with isolates from Hong Kong, China. No M1_UK new clone strains were found. The ST1274 isolates of emm1 were newly discovered in 2020‒2024, and belonged to a separate phylogenetic clade. ConclusionGAS strains isolated from children with respiratory tract infections in a tertiary hospital in Jinshan District of Shanghai exhibit a high resistance to erythromycin, clindamycin, and tetracycline. It is recommended that the clinical treatments change to use other antimicrobial drugs, such as penicillin, third-generation cephalosporins, and fluoroquinolones. During 2020‒2024, a new ST1274 clone strain is discovered in emm1 GAS isolates, without M1_UK new clone strains being found. It is essential to continuously concern locally prevalent GAS strains and perform early identification of MLST types to promptly monitor the internal changes of the bacterial population and potential prevalence of new clones.