Artificial intelligence （AI） and population pharmacokinetics （PPK） technologies have demonstrated significant potential in the personalized medication of immunosuppressants after organ transplantation, enabling precise prediction of drug dosages. This article provides a comprehensive review of the application status of AI and PPK in the individualized administration of immunosuppressants after organ transplantation， focuses on monitoring blood drug concentration， predicting efficacy/adverse reactions， and establishing individualized dosing models for organ transplant recipients after immunosuppressant administration， and analyzes and compares the application characteristics of different methods in different organ transplant patients as well as the integration and future development of AI and PPK technologies. AI and PPK technologies can not only significantly reduce the dependence on human resources， but also greatly improve the level of individualized treatment of immunosuppressants after organ transplantation， and reduce the discomfort and burden caused by frequent blood concentration monitoring to patients.

Glucagon-like peptide-1 （GLP-1） receptor agonists are a novel class of antidiabetic drugs that also possess lipid- lowering and cardiovascular protective effects， with liraglutide and semaglutide being their representative medications. Based on a systematic literature search， this review summarizes the lipid-lowering mechanisms by which liraglutide and semaglutide exert direct effects on the liver and kidney （regulating autophagy， key lipid metabolism pathways， reverse cholesterol transport， etc.）， direct actions on adipose tissue （affecting adipocyte proliferation and differentiation， expression of lipid metabolism proteins， and gene transcription）， activation of sympathetic pathways through the central nervous system， and modulation of the gut microbiota. Additionally， it summarizes the clinical evidence of their lipid-lowering effects in populations with type 2 diabetes mellitus， overweight individuals， and others. These findings indicate that GLP-1 receptor agonists exert lipid-lowering effects by acting on multiple tissues or systems， providing crucial evidence for further elucidating the molecular mechanisms of these drugs in lipid regulation and exploring potential new ideas for their clinical applications.

Objective To construct a non-trace deletion mutant of exlA in Pseudomonas aeruginosa strain NY8755(NY8755ΔexlA)and investigate the basic characteristics of pore-forming toxin ExlA.Methods The NY8755ΔexlA was constructed using the secondary homologous recombination method.C57BL/6J female mice ages 6 to 8 weeks were infected with NY8755 and NY8755 ΔexlA via aerosolized intratraheal inoculation respectively.Within 7 days of infection,the survival and weight changes of the mice were observed and recorded before the proinflammatory cytokines in the bronchoal-veolar lavage fluid(BALF)of the infected mice in the two groups were detected.Results The sequencing results showed that NY8755 ΔexlA was constructed.After 1×107 CFU NY8755 and NY8755 ΔexlA were infected,all the mice in the wild-type strain group died within 48 hours,while those in the mutant strain group began to die after 48 hours,and 40%of them remained alive 7 days later.The weight of surviving mice in the mutant strain group decreased but recovered gradually.After 12 hours of infection,there were more bloody exudates(redder in color)in the BALF of the wild-type strain group than in the mutant strain group,and the contents of proinflammatory cytokines interleukin-1β(IL-1β)and interleukin-17A (IL-17A)were significantly different. Conclusion Pseudomonas aeruginosa pore-forming toxin ExlA is the key pathogenic virulence factor of the exlA-positive Pseudomonas aeruginosa,which can significantly affect the survival status of mice and cause obvious inflammation in mice. Very little information is available on the action mechanisms of ExlA. In this study, The NY8755ΔexlA and the C57BL/6J mouse models infected with NY8755 and NY8755ΔexlA have been constructed that may be used for the investigation of pathogenesis of exlA-positive Pseudomonas aeruginosa.

ObjectiveTo investigate the effects of Aconiti Coreani Radix and Typhonii Rhizoma on the urinary metabolites of gerbils with stroke by non-targeted metabolomics technique， and then to clarify the mechanism of the two， as well as their similarities and differences. MethodTwenty-four gerbils were randomly divided into control group（CG）， model group（MG）， Aconiti Coreani Radix group（RA） and Typhonii Rhizoma group（RT）. Except for the CG， ischemic stroke model was constructed using right unilateral ligation of gerbil carotid artery in the remaining groups. Except for the CG and MG， rats in the other groups received whole powder suspension（0.586 mg·g^-1） was administered for 14 days. The neurological deficit in each group was scored by Longa scoring on days 0， 3， 7 and 14. After the end of administration， the serum， brain tissue and urine of gerbils in each group were collected， and the rate of cerebral infarction was detected by 2，3，5-triphenyltetrazolium chloride（TTC）， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， malondialdehyde（MDA）， superoxide dismutase（SOD）， glutathione（GSH）， and nitric oxide（NO） in serum and brain tissue were determined by enzyme-linked immunosorbent assay（ELISA）. The urine metabolomics of gerbils in each group was studied by ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， and the data were processed by multivariate statistical analysis， and differential metabolites were screened based on value of variable importance in the projection（VIP） of the first principal component>1 and t-test P<0.05. Metabolic pathway analysis of the screened differential metabolites was performed using Kyoto Encyclopedia of Genes and Genomes（KEGG） database and Metaboanalyst 5.0. ResultCompared with the CG， the neurological deficit score was significantly increased in the MG（P<0.05）， compared with the MG， the neurological deficit scores in the RA and RT were significantly reduced after 7 d and 14 d（P<0.05）. Compared with the CG， the rate of cerebral infarction was significantly increased in the MG（P<0.05）， compared with the MG， the rates of cerebral infarction in the RA and RT were significantly reduced（P<0.05）. Compared with the CG， the levels of IL-6， TNF-α， and MDA in the serum and brain tissue of gerbils from the MG were significantly increased（P<0.05）， and the levels of SOD， GSH and NO were significantly reduced（P<0.05）. Compared with the MG， Aconiti Coreani Radix and Typhonii Rhizoma could down-regulate the levels of IL-6， TNF-α and MDA， and up-regulated the levels of SOD， GSH and NO. A total of 112 endogenous differential metabolites were screened by urine metabolomics， of which 16 and 26 metabolites were called back by Aconiti Coreani Radix and Typhonii Rhizoma， and could be used as potential biomarkers for both treatments in stroke gerbils， respectively. The results of the pathway analysis showed that both Aconiti Coreani Radix and Typhonii Rhizoma had regulatory effects on arginine and proline metabolism， pyrimidine metabolism， and aminoacyl-tRNA biosynthesis. In addition， Aconiti Coreani Radix could also regulate riboflavin metabolism， Typhonii Rhizoma could also regulate purine metabolism， glycine， serine and threonine metabolism， arachidonic acid metabolism， biosynthesis of pantothenate and coenzyme A， and β-alanine metabolism. ConclusionBoth Aconiti Coreani Radix and Typhonii Rhizoma have better therapeutic effects on stroke， with Aconiti Coreani Radix having stronger effects. From the metabolomics results， the main metabolic pathways regulated by Aconiti Coreani Radix involve amino acid metabolism， oxidative stress and so on， while Typhonii Rhizoma mainly involve amino acid metabolism， lipid metabolism， energy metabolism， etc.

Postoperative pain seriously affects the recovery process of patients, resulting in prolonged hospital stay and increased care costs. Appropriate application of patient-controlled analgesia devices can effectively relieve perioperative acute pain. In 1994 patient-controlled analgesia began to be used in Peking Union Medical College Hospital, and the Acute Pain Service Working Group was established in 2004. With the cooperation of anesthesiologists and specialist nurses, the group jointly has implemented the whole process and standardized management based on patient-controlled analgesia, and constantly improved and innovated working methods, laying a solid foundation for the development of postoperative pain management. This paper systematically reviews and summarizes the work from the aspects of clinical focus, nursing management experience, promotion and dissemination of pain treatment concepts, and development of acute pain service model under the new situation, with the hope of providing valuable reference for comprehensively strengthening pain management in the process of diagnosis and treatment, and enhancing patients' satisfaction with perioperative analgesia services.

Objective:To explore the regulatory role of the melanin-concentrating hormone (MCH) neural pathway from the lateral hypothalamus (LHA) to the nucleus accumbens (NAc) in modulating anxiety-like behavior in mice.Methods:Totally 37 male SPF-grade C57BL/6J mice, aged 6 to 8 weeks and weighed 18-22 g, were used for the following experiment: (1) Five mice received an injection of Fluoro-Gold (FG) into the NAc, followed by retrograde tracing combined with immunofluorescence staining after one week to observe the coexistence of FG and MCH immunopositive neurons in the LHA.(2)Thirty-two mice were injected with adeno-associated virus which could activate the MCH neurons into the LHA.After two weeks, they were randomly divided into four groups and received different drug injections: normal saline (NS, intraperitoneal injection)+ NS (1.5 μL, injection in the NAc) group, NS(intraperitoned injection) + SNAP94847 (SNAP, 2 mg/mL, 1.5 μL, injection in the NAc) group, chlorprothixene N-oxide (CNO, 0.15 mg/kg, intraperitoned injection) + NS(1.5 μL, injection in the NAc) group, and CNO(intraperitoned injection) + SNAP(1.5 μL injection in the NAc) group, and the SNAP94847 was an antagonist for MCH typel receptor.The open field test (OFT), elevated plus maze (EPM), and marble burial test (MBT) were employed to assess the impact of chemogenetic activation of MCH neurons on anxiety-related behavior in mice.Results:(1) The results of FG retrograde tracing combined with immunofluorescence histochemistry showed that MCH neurons in the LHA project their neural fibers to NAc neurons.(2) In the chemogenetic experiment, there was no significant interaction effect between CNO and SNAP in terms of the duration of stay ( Finteraction=2.899, P>0.05) and the distance moved ( Finteraction=1.603, P>0.05) in the central area during OFT experiments.However, the main effects of both CNO and SNAP intervention were significant in the duration of stay ( FCNO=6.767, FSNAP=7.656, both P<0.05) and the distance moved ( FCNO=12.480, FSNAP=7.999, both P<0.01) in the central area.Compared to the NS+ NS group, mice in the CNO+ NS group exhibited a shortened duration of stay ((89.00±19.16)s, (63.75±13.58)s, P<0.05) and a decrease in distance moved ((593.79±108.18)cm, (426.81±66.14)cm, P<0.05) in the central area.In contrast, mice in the CNO+ SNAP group had an extended duration of stay ((87.38±16.57)s) and an increase in distance moved ((569.27±73.20)cm) in the central area compared to the CNO+ NS group.There was no significant interaction effect between CNO and SNAP in the number of entries ( Finteraction=2.79, P>0.05) and the dwell time ( Finteraction=2.871, P>0.05) into the open arms of EPM experiments.However, the main effects of both CNO and SNAP interventions in the number of entries ( FCNO=10.43, P<0.01; FSNAP=4.96, P<0.05) and the dwell time ( FCNO=5.232, FSNAP=7.597, both P<0.05) into the open arms were significant.Compared to the NS+ NS group, mice in the CNO+ NS group showed a decrease in the number of entries ((13.13±3.36), (7.63±3.70), P<0.01) and a decrease in open arm dwell time ((37.68±11.37) s, (22.98±7.00) s, P<0.05) into the open arms.The CNO+ SNAP group had an increased number of entries (12.00±3.02) and an increased dwell time ((39.41±10.58)s) into the open arms compared to the CNO+ NS group(both P<0.05).There was no significant interaction effect between CNO and SNAP in the MBT experiment ( Finteraction=2.746, P>0.05).However, the main effects of both CNO and SNAP interventions were significant ( FCNO=8.125, P<0.01; FSNAP=5.383, P<0.05).Compared to the NS+ NS group, the number of buried beads increased in the CNO+ NS group ((16.13±2.10), (11.88±3.23), P<0.05).Conversely, the number of buried beads decreased in the CNO+ SNAP group compared to the CNO+ NS group ((12.38±2.33), (16.13±2.10), P<0.05). Conclusion:Enhanced activity in the MCHergic neural pathway from LHA to NAc can promote anxiety-like behavior in mice, providing new insights into the mechanisms underlying anxiety.

Objective To compare the success rates of two methods for endobronchial intubation:the left-sided double-lumen tube(DLT)rotated 90° counter-clockwise with the patient head at the mid positon and the tube rotated 180°counter-clockwise with the patient head turned to the right.Methods Six hundred and forty-eight patients were enrolled in this study,who were to undergo elective thoracic surgery by left-sided DLT intuba-tion in the Peking Union Medical College Hospital from December 2021 to June 2022.They were randomized into a 90° group and a 180° group,with 324 patients in each group.In the 90° group,with the patient head kept at the mid position,the left-sided DLT was advanced until the bronchial cuff passed the vocal cords and then rotated 90° counter-clockwise.In the 180°group,with the left mandible angle of each patient in the straight line with the ster-num,the tube was advanced until the bronchial cuff passed the vocal cords and then rotated 180° counter-clock-wise.The intubation success rate and the intubation-related complications such as carina mucosal injuries were com-pared between the two groups.Results The 648 patients included 336 males and 312 females,with the age ran-ging from 39.0 to 75.0 years old and the average age of(54.6±9.0)years old.The success rate of first intubation was 80.3% in the 90°group and 75.0% in the 180°group,which showed no significant difference(P =0.109).The success rate of second intubation was higher in the 180°group than in the 90°group(P<0.001).The rate of carina mucosal injuries was 23.8% in the 90° group and 25.6% in the 180° group,which showed no significant difference(P =0.585).Conclusions Compared with the conventional method(90°),the intubation of the left-sided DLT rotated 180° counter-clockwise with the patient head turned to the right cannot improve the success rate of the first intubation.However,it could improve the success rate of reintubation as a remedy.

Objective:To prepare a humanized monoclonal antibody against periostin and establish a stable cell line.Meth-ods:Based on anti-periostin mouse monoclonal antibody developed by our laboratory,total RNA was extracted,and variable region sequences were obtained by RT-PCR amplification of VH and VL genes.The mouse antibody CDR region was transplanted into the human antibody framework receptor region,and the gene was subcloned into the expression vector PATX-GS2,and stably transfected into CHO cells.Monoclonal cell lines were obtained by MSX pressure screening and limited dilution.Results:VH and VL genes were amplified by RT-PCR,and the sequence of the light and heavy chain variable region were determined.Antibody humanization were successfully stablished by CDR transplantation method a murine antibody to a human framework,and a eukaryotic expression plasmid was constructed,which was transfected into CHO cells for expression,and human anti-periostin antibody was successfully obtained.ELISA and Western blot results showed that the humanized antibody had good anti-periostin activities and binding affinity.Conclu-sion:In this study,anti-periostin humanized monoclonal antibody has been successfully prepared,which can specifically bind to peri-ostin proteins in vivo and have biological activity,providing scientific data for the precise treatment of retinal fibrosis,tissue and organ fibrosis,and malignant tumors.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:Exploring the efficacy and safety of bridging blinatumomab (BiTE) in combination with chimeric antigen receptor T (CAR-T) cell therapy for the treatment of adult patients with acute B-cell lymphoblastic leukemia (B-ALL) .Methods:Clinical data from 36 adult B-ALL patients treated at the First Affiliated Hospital of Suzhou University from August 2018 to May 2023 were retrospectively analyzed. A total of 36 cases were included: 18 men and 18 women. The median age was 43.5 years (21-72 years). Moreover, 21 cases of Philadelphia chromosome-positive acute lymphoblastic leukemia were reported, and 16 of these cases were relapsed or refractory. Eighteen patients underwent blinatumomab bridging followed by CAR-T cell therapy, and 18 patients received CAR-T cell therapy. This study analyzed the efficacy and safety of treatment in two groups of patients.Results:In the BiTE bridge-to-CAR-T group, 16 patients achieved complete remission (CR) after BiTE immunotherapy, with a CR rate of 88.9%. One month after bridging CAR-T therapy, bone marrow examination showed a CR rate of 100.0%, and the minimal residual disease (MRD) negativity rate was higher than the nonbridging therapy group (94.4% vs. 61.1%, Fisher, P=0.041). The incidence of cytokine release syndrome and other adverse reactions in the BiTE bridge-to-CAR-T group was lower than that in the nonbridging therapy group (11.1% vs. 50.0%, Fisher, P=0.027). The follow-up reveals that 13 patients continued to maintain MRD negativity, and five patients experienced relapse 8.40 months (2.57-10.20 months) after treatment. Two of five patients with relapse achieved CR after receiving the second CAR-T cell therapy. In the nonbridging therapy group, 10 patients maintained continuous MRD negativity, 7 experienced relapse, and 6 died. The 1 year overall survival rate in the BiTE bridge-to-CAR-T group was higher than that in the nonbridging therapy group, with a statistically significant difference at the 0.1 level (88.9%±10.5% vs. 66.7%±10.9%, P=0.091) . Conclusion:BiTE bridging CAR-T cell therapy demonstrates excellent efficacy in adult B-ALL treatment, with a low recent recurrence rate and ongoing assessment of long-term efficacy during follow-up.