The combination of Aidi Injection(ADI) and doxorubicin(DOX) is a common strategy in the treatment of cancer, which can achieve synergistic anti-tumor effects while attenuating the cardiotoxicity caused by DOX. This study aims to investigate the mechanism of ADI in attenuating DOX-induced cardiotoxicity by multi-omics. DOX was used to induce cardiotoxicity in mice, and the cardioprotective effects of ADI were evaluated based on biochemical indicators and pathological changes. Based on the results, transcriptomics, proteomics, and metabolomics were employed to analyze the changes of endogenous substances in different physiological states. Furthermore, data from multiple omics were integrated to screen key regulatory pathways by which ADI attenuated DOX-induced cardiotoxicity, and important target proteins were selected for measurement by ELISA kits and immunohistochemical analysis. The results showed that ADI significantly reduced the levels of cardiac troponin T(cTnT) and N-terminal pro-B-type natriuretic peptide(NT-proBNP) and effectively ameliorated myocardial fibrosis and intracellular vacuolization, indicating that ADI showed therapeutic effect on DOX-induced cardiotoxicity. The transcriptomics analysis screened out a total of 400 differentially expressed genes(DEGs), which were mainly enriched in inflammatory response, oxidative stress, and myocardial fibrosis. After proteomics analysis, 70 differentially expressed proteins were selected, which were mainly enriched in the inflammatory response, cardiac function, and energy metabolism. A total of 51 differentially expressed metabolites were screened by the metabolomics analysis, and they were mainly enriched in multiple signaling pathways, including the inflammatory response, lipid metabolism, and energy metabolism. The integrated data of multiple omics showed that linoleic acid metabolism, arachidonic acid metabolism, and glycerophosphate metabolism pathways played an important role in DOX-induced cardiotoxicity, and ADI may exert therapeutic effects by modulating these pathways. Target validation experiments suggested that ADI significantly regulated abnormal protein levels of cyclooxygenase-1(COX-1), cyclooxygenase-2(COX-2), prostaglandin H2(PGH2), and prostaglandin D2(PGD2) in the model group. In conclusion, ADI may attenuate DOX-induced cardiotoxicity by regulating linoleic acid metabolism, arachidonic acid metabolism, and glycerophosphate metabolism, thus alleviating inflammation of the body.
Doxorubicin/toxicity* ; Animals ; Mice ; Cardiotoxicity/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Proteomics ; Metabolomics ; Injections ; Humans ; Multiomics

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

Objective:To investigate the potential diagnostic value of peripheral blood soluble programmed cell death protein 1 (sPD-1) and soluble programmed cell death protein ligand 1 (sPD-L1) in acute rejection (AR) following liver transplantation using a rat model.Methods:A rat liver transplantation AR model was established, with the AR group (Lewis→BN) set as the experimental group (n=6) and the non-AR group (BN→BN) as the control group (n=6). Peripheral blood sPD-1 and sPD-L1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA) at 1 day before transplantation and at 1, 3, and 7 days postoperatively. On postoperative day 7, the expression levels of PD-1 and PD-L1 in liver tissues were detected by immunohistochemistry (IHC). Independent samples t-test and repeated measures ANOVA were used to compare the results between the two groups. Pearson correlation analysis was conducted to evaluate the relationship between sPD-1, sPD-L1, the sPD-1/sPD-L1 ratio, and the rejection activity index.Results:On postoperative day 7, the experimental group exhibited significantly higher peripheral sPD-1 levels (218.59±36.88 vs. 164.95±15.82 ng/L) and a higher sPD-1/sPD-L1 ratio (0.44±0.12 vs. 0.36±0.07), but lower sPD-L1 levels (379.56±73.41 vs. 423.64±96.55 ng/L) compared to the control group (all P<0.05). Correlation analysis revealed a significant positive correlation between sPD-1 levels and the rejection activity index ( r=0.680, P<0.05), as well as between the sPD-1/sPD-L1 ratio and the rejection activity index ( r=0.795, P<0.01), while no correlation was observed between sPD-L1 levels and the rejection activity index. IHC demonstrated positive PD-1 and PD-L1 expression in the liver tissues of the experimental group, whereas the control group showed negative expression. Conclusion:Peripheral blood sPD-1 levels and the sPD-1/sPD-L1 ratio are significantly associated with AR after liver transplantation in rats, suggesting their potential as biomarkers for diagnosing AR in liver transplant recipients.

Objective:To summarize the clinical characteristics, diagnostic and therapeutic approaches, and prognosis of posttransplant lymphoproliferative disease (PTLD) following kidney transplantation.Methods:A retrospective case series analysis was conducted on 7 PTLD patients after kidney transplantation treated in the Department of Transplant Oncology, Tianjin First Central Hospital between January 2018 and December 2023. Clinical features, laboratory findings, imaging and pathological characteristics, treatment modalities, and outcomes were analyzed.Results:Among 7 PTLD patients, there were 5 male and 2 females with a median age of 41 (17-65) years. The median time of onset after operation was 4 (0.5-11) years. Among them, 2 patients had early onset (<1 year post-transplantation) and 5 patients had late onset (>1 year). The clinical manifestations included abdominal mass in 4 cases, anemia in 4 cases, fever in 3 cases, lymphadenopathy in 4 cases, gastrointestinal bleeding in 1 case, abdominal pain in 2 cases, and intestinal obstruction in 2 cases. Pathological types included diffuse large B-cell lymphoma in 4 cases, Burkitt lymphoma in 1 case, marginal zone lymphoma in 1 case, and polymorphic PTLD in 1 case. Reducing the immunosuppressant level was the basal treatment plan, and rituximab, chemotherapy, surgery, radiotherapy and CD19-targeted chimeric antigen receptor therapy were given according to the pathological classification. Until the date of submission, 2 patients had died, 4 had a complete response, and 1 had a partial response. None of the patients had acute rejection, and 1 patient had chronic renal insufficiency.Conclusions:PTLD after kidney transplantation presents with nonspecific manifestations, necessitating prompt imaging and histopathological evaluation for definitive diagnosis. At the same time, a series of measures should be given to improve the prognosis, including discontinuous use of anti-metabolic drugs, dosage decline of calcitric phosphatase inhibitor by 50% or convert it to sirolimus treatment, and corresponding treatment according to the specific conditions of the recipient.

The left maxilla of a patient was resected because of tumor,and the defect was reconstruted with fibular transplantation.The autonomous dental implant robot technology was used to achieve precise implantation of multiple implants and immediate denture restoration within the limited left maxilla.The surgery was minimally invasive and efficient,and significantly reducing patient post-operative discomfort.The final restoration was completed 6 months after surgery.

Objective:To investigate the correlation between interleukin-10, albumin levels and short-term prognosis in patients with acute lung injury.Methods:A retrospective study was conducted to collect data on 150 patients with acute lung injury admitted to the Fourth People′s Hospital of Longgang District, Shenzhen from January 2021 to December 2023. The short-term prognosis was evaluated based on the mortality rate within 28 d of admission, and the patients were divided into a mortality group 53 cases and a survival group 97 cases. General information, levels of interleukin-10 and albumin within 24 h of admission, and other laboratory indicators were compared between the two groups, with a focus on analyzing the correlation between interleukin-10, albumin levels and the short-term prognosis of patients.Results:Murray lung injury score, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score and levels of C-reactive protein, interleukin-10 in the mortality group were higher than those in the survival group: (2.27 ± 0.36) scores vs. (1.98 ± 0.28) scores, (22.72 ± 3.27) scores vs. (19.85 ± 3.12) scores, (106.27 ± 14.22) mg/L vs. (93.22 ± 15.27) mg/L, (51.75 ± 8.12) ng/L vs. (46.27 ± 9.47) ng/L, the levels of platelet and albumin were lower than those in the survival group: (186.67 ± 23.11) ×10 9/L vs. (203.25 ± 25.36) ×10 9/L, (27.86 ± 4.75) g/L vs. (32.21 ± 5.61) g/L, with statistical significant differences ( P<0.05). Cox regression analysis showed that the mortality risk of patients with acute lung injury was related to Murray lung injury score, APACHEⅡ score, platelet, C-reactive protein, interleukin-10 and albumin levels at admission ( P<0.05). Restricted cubic spline (RCS) analysis and interaction testing found that the mortality risk of patients with acute lung injury showed a non-linear dose-response relationship with serum interleukin-10 and albumin levels ( P<0.05), and the two had a negative interaction with the mortality risk of patients. The interleukin-10, albumin-assisted Murray lung injury score, APACHE Ⅱ score, platelet and C-reactive protein were used to construct a nomogram prediction model, and the decision curve and nomogram measurement model were drawn. The model has certain predictive value for the short-term risk of death in patients with acute lung injury. Conclusions:The short-term mortality risk in patients with acute lung injury may be related to abnormal levels of interleukin-10 and albumin, which can assist in the early screening of high-risk mortality patients and serve as clinical intervention targets.

According to the work goals and tasks determined by edition outline of the Chinese Pharmacopoeia 2025 Edition, the Chinese Pharmacopoeia 2025 Edition has been completed. Among them, 52 new pharmaceutical excipients monographs have been added, an increase of 15.5% compared with the 2020 Edition, and the total number has reached 387. This article focuses on the general framework and the main characteristics of the standards of pharmaceutical excipients in the Chinese Pharmacopoeia 2025 Edition, which can contribute to accurately understand and utilize the standards in Chinese Pharmacopoeia.

Objective: To explore the association between parent-child connectedness and romantic relationships of secondary vocational school students and the moderating effect of peers romantic behavior, providing scientific basis for family and school health education. Methods: From March to April 2021，2 426 students from six secondary vocational and technical schools in Shanghai and Shaanxi Province were selected to conduct the survey by combining convenience sampling and cluster sampling.Electronic questionnaires were used to collect data on students family characteristics,oneself and peer romantic behaviors, and parent-child bonding. The t-test was employed for inter group comparisons, and binary Logistic regression analysis was conducted to examine the relationship between parent-child bonding levels, peer romantic behavior, and the romantic behavior of secondary vocational students. Results: The mother-child connection (2.63±0.77) was higher than that of father-child connection (2.48±0.78), with statistically significant difference ( t =6.83, P <0.01). Multivariable Logistic regression showed that overall father-child connectedness was negatively associated with students romantic relationships( OR =0.86，95% CI =0.76-0.97， P =0.02)and was only associated to girls romantic relationships when stratified by gender( OR =0.79，95% CI =0.66-0.93， P =0.01). Peers romantic relationships were positively associated with students romantic relationships ( OR =3.19-5.12, all P <0.01), and there was a moderating effect of the association between maternal connectedness and boys romantic relationships ( OR =1.67, 95% CI =1.05-2.66, P =0.03). Among boys without romantic peers, mother-child connectedness was negatively associated with their romantic relationships ( OR = 0.60 , 95% CI =0.36-0.99, P <0.05). In the total sample of Shanghai and girls of Shaanxi, father-child connectedness was negatively correlated with the romantic relationships of secondary vocational school students ( OR =0.84,0.65,95% CI =0.71-1.00,0.50-0.85,both P <0.05). Peer romantic relationships exhibited a negative moderating effect on the influence of mother-child connectedness on the romantic relationships of males in Shanghai ( OR =1.91, 95% CI =1.03-3.57, P <0.05). Conclusions The father-daughter connectedness is negatively correlated with girls romantic behavior, and peer romantic behavior weakens the correlation between mother-child connectedness and boys romantic behavior. Efforts should be made to enhance the parent-child connectedness of secondary vocational students and their ability to cope with peer influence, providing proper guidance for adolescents heterosexual interactions.