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.

Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Objective The purpose is to explore the status quo and management countermeasures of interdepartmental consultation of inpatients in hospitals.Methods Collect the inter-departmental consultation data of a hospital from 2020 to 2022 and analyse the factors influencing intersectoral consultations.Results From 2020 to 2022,a total of 201 058 inpatients applied for general consultation in the hospital,with a daily average of 183.45.The departments with the largest number of applications are emergency department,general surgery center,digestive center,neurology department,and heart center,and the proportion of internal medicine system is higher than that of surgical system every year.179 876 cases were invited for general consultation in the hospital,with an average of 164.12 cases per day.The largest number of invited departments are the heart center,the digestion center,the endocrinology department,the general surgery center,and the internal medicine teaching and research department,and the proportion of the internal medicine system is higher than the surgical system every year.Within three years,the response rate of the whole hospital consultation application increased year by year,and the timely rate of consultation increased year by year,and the timely rate of consultation in the medical system was higher than that in the surgical system every year.Conclusion Systematically analyzing the consultation data of medical institutions,grasping the actual needs of inter-departmental consultation of inpatients from different departments and their attitudes to consultation can provide reference basis for optimizing the consultation service process,improving the efficiency and quality of consultation service.

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 investigate the effect of erythroid differentiation associated gene(EDAG)on hematopoietic stem/progenitor cells(HSPCs)under chronic inflammation.Methods In this study,EDAG-/-and wild type(WT)mice were divided into the experiment group and control group.An infectious chronic inflammation model was established via multiple intraperitoneal injections of Listeria monocytogenes(LM),while a sterile chronic inflammation model was generated via multiple intraperitoneal injections of polyinosinic-polycytidylic acid[Poly(I∶C)].The effect of EDAG on HSPCs was explored under chronic inflammation conditions.Results In the LM repeated infection model,EDAG deletion led to a decrease in HSPCs and long-term hematopoietic stem cells(LT-HSCs)in mice as well as a significant bias towards myeloid differentiation in peripheral blood.Similarly,EDAG knockout also resulted in reduced numbers of HSPCs and decreased colony-forming ability in aseptic chronic inflammation models.Conclusion EDAG deficiency accelerates HSPC depletion in young mice under chronic inflammation,indicating strong protection of EDAG against HSPC damage induced by chronic inflammation.

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.

Objective To compare the difference of peripheral blood adiponectin and CD4+T cell subsets between patients with a-cute gouty arthritis and healthy controls,to explore the correlation between adiponectin and serum uric acid,disease activity,CT4+T cell subsets and some cytokines in patients with gout.Methods The clinical data(including general data,neutrophils,erythrocyte sedimen-tation rate,C-reactive protein,blood uric acid,CT4+T cell subsets and some cytokines)of acute gout group(n=90)and healthy con-trol group(n=72)were collected.The level of adiponectin in peripheral blood of two groups were detected,and the differences of adi-ponectin and CD4+T cell subsets between the two groups were compared;the correlation between adiponectin and clinical data was ana-lyzed.Results The levels of serum adiponectin in the acute gout group were significantly lower than those in the healthy control group(P＜0.001),and the levels of Th2,Thl7,Th17/Treg were significantly higher than those in the healthy control group(P＜0.05),while the levels of Treg and Th1/Th2 were significantly lower than those in the healthy control group(P＜0.05).In the acute gout group,adiponectin was negatively correlated with neutrophil,erythrocyte sedimentation rate and C-reactive proten(r=-0.244,P＜0.05;r=-0.311,P＜0.05;r=-0.506,P＜0.001),there was no correlation with serum uric acid.In acute gout group,adiponectin was posi-tively correlated with Th1 and Th1/Th2(r=0.252,P＜0.05;r=0.218,P＜0.05).In acute gout group,adiponectin in peripheral blood was positively correlated with interleukin-2(IL-2),interleukin-4(IL-4)and interleukin-10(IL-10)(r=0.323,P＜0.05;r=0.377,P＜0.05;r=0.359,P＜0.05).There was a negative correlation between interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)(r=-0.265,P＜0.05;r=-0.299,P＜0.05).Multiple linear regression analysis showed that adiponectin in the acute gout group was negatively correlated with erythrocyte sedimentation rate,C-reactive protein,IL-6 and TNF-α(BESR=-12.541,P=0.003;BCRP=-8.256,P=0.024;BIL-6=-15.907,P=0.037;BTNF-α=-79.770,P=0.040),but positively correlated with Th1(BTh1=2.959,P=0.006).Conclusion The levels of adiponectin in the peripheral blood of patients with acute gouty arthritis were decreased,the levels of Th2 and Th17 were increased,and the levels of Treg were decreased.The decrease of adi-ponectin was related to the immunological disorder and inflammation in the patients with acute gouty arthritis.

Background: The emergence of the severe acute respiratory syndrome coronavirus 2 omicron variant has been triggering the new wave of coronavirus disease 2019 (COVID-19) globally. However, the risk factors and outcomes for radiological abnormalities in the early convalescent stage (1 month after diagnosis) of omicron infected patients are still unknown. Methods: Patients were retrospectively enrolled if they were admitted to the hospital due to COVID-19. The chest computed tomography (CT) images and clinical data obtained at baseline (at the time of the first CT image that showed abnormalities after diagnosis) and 1 month after diagnosis were longitudinally analyzed. Uni-/multi-variable logistic regression tests were performed to explore independent risk factors for radiological abnormalities at baseline and residual pulmonary abnormalities after 1 month. Results: We assessed 316 COVID-19 patients, including 47% with radiological abnormalities at baseline and 23% with residual pulmonary abnormalities at 1-month follow-up. In a multivariate regression analysis, age ≥ 50 years, body mass index ≥ 23.87, days after vaccination ≥ 81 days, lymphocyte count ≤ 1.21 × 10 -9 /L, interleukin-6 (IL-6) ≥ 10.05 pg/mL and IgG ≤ 14.140 S/CO were independent risk factors for CT abnormalities at baseline. The age ≥ 47 years, presence of interlobular septal thickening and IL-6 ≥ 5.85 pg/mL were the independent risk factors for residual pulmonary abnormalities at 1-month follow-up. For residual abnormalities group, the patients with less consolidations and more parenchymal bands at baseline could progress on CT score after 1 month. There were no significant changes in the number of involved lung lobes and total CT score during the early convalescent stage. Conclusion The higher IL-6 level was a common independent risk factor for CT abnormalities at baseline and residual pulmonary abnormalities at 1-month follow-up. There were no obvious radiographic changes during the early convalescent stage in patients with residual pulmonary abnormalities.