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.

Purpose::Ischemia and hypoxia are the main factors limiting limb replantation and transplantation. Static cold storage (SCS), a common preservation method for tissues and organs, can only prolong limb ischemia time to 4 - 6 h. The normothermic machine perfusion (NMP) is a promising method for the preservation of tissues and organs, which can extend the preservation time in vitro by providing continuous oxygen and nutrients. This study aimed to evaluate the difference in the efficacy of the 2 limb preservation methods. Methods::The 6 forelimbs from beagle dogs were divided into 2 groups. In the SCS group ( n = 3), the limbs were preserved in a sterile refrigerator at 4 °C for 24 h, and in the NMP group ( n = 3), the perfusate prepared with autologous blood was used for the oxygenated machine perfusion at physiological temperature for 24 h, and the solution was changed every 6 h. The effects of limb storage were evaluated by weight gain, perfusate biochemical analysis, enzyme-linked immunosorbent assay, and histological analysis. All statistical analyses and graphs were performed using GraphPad Prism 9.0 one-way or two-way analysis of variance. The p value of less than 0.05 was considered to indicate statistical significance. Results::In the NMP group, the weight gained percentage was 11.72% ± 4.06%; the hypoxia-inducible factor-1α contents showed no significant changes; the shape of muscle fibers was normal; the gap between muscle fibers slightly increased, showing the intercellular distance of (30.19 ± 2.83) μm; and the vascular α-smooth muscle actin (α-SMA) contents were lower than those in the normal blood vessels. The creatine kinase level in the perfusate of the NMP group increased from the beginning of perfusion, decreased after each perfusate change, and remained stable at the end of perfusion showing a peak level of 4097.6 U/L. The lactate dehydrogenase level of the NMP group increased near the end of perfusion and reached the peak level of 374.4 U/L. In the SCS group, the percentage of weight gain was 0.18% ± 0.10%, and the contents of hypoxia-inducible factor-1α increased gradually and reached the maximum level of (164.85 ± 20.75) pg/mL at the end of the experiment. The muscle fibers lost their normal shape and the gap between muscle fibers increased, showing an intercellular distance of (41.66 ± 5.38) μm. The contents of vascular α-SMA were much lower in the SCS group as compared to normal blood vessels.Conclusions::NMP caused lesser muscle damage and contained more vascular α-SMA as compared to SCS. This study demonstrated that NMP of the amputated limb with perfusate solution based on autologous blood could maintain the physiological activities of the limb for at least 24 h.

Objective: To explore the safety and efficacy of excimer laser coronary angioplasty (ELCA) for the treatment of degenerated great saphenous vein graft (SVG). Methods: This is a single-center, prospective, single-arm study. Patients, who were admitted to the Geriatric Cardiovascular Center of Beijing Anzhen Hospital from January 2022 to June 2022, were consecutively enrolled. Inclusion criteria were recurrent chest pain after coronary artery bypass surgery (CABG), and coronary angiography confirmed that the SVG stenosis was more than 70% but not completely occluded, and interventional treatment for SVG lesions was planned. Before balloon dilation and stent placement, ELCA was used to pretreat the lesions. Optical coherence tomography (OCT) examination was performed and postoperative index of microcirculation resistance (IMR) were assessed after stent implantation. The technique success rate and operation success rate were calculated. The technique success was defined as the successful passage of the ELCA system through the lesion. Operation success was defined as the successful placement of a stent at the lesion. The primary evaluation index of the study was IMR immediately after PCI. Secondary evaluation indexes included thrombolysis in myocardial infarction (TIMI) flow grade, corrected TIMI frame count (cTFC), minimal stent area and stent expansion measured by OCT after PCI, and procedural complications (Ⅳa myocardial infarction, no reflow, perforation). Results: A total of 19 patients aged (66.0±5.6) years were enrolled, including 18 males (94.7%). The age of SVG was 8 (6, 11) years. The length of the lesions was greater than 20 mm, and they were all SVG body lesions. The median stenosis degree was 95% (80%, 99%), and the length of the implanted stent was (41.7±16.3)mm. The operation time was 119 (101, 166) minutes, and the cumulative dose was 2 089 (1 378, 3 011)mGy. The diameter of the laser catheter was 1.4 mm, the maximum energy was 60 mJ, and the maximum frequency was 40 Hz. The technique success and the operation success rate were both 100% (19/19). The IMR after stent implantation was 29.22±5.95. The TIMI flow grade of patients after ELCA and stent implantation was significantly improved (all P>0.05), and the TIMI flow grade of all patients after stent implantation was Grade Ⅲ. The cTFC decreased significantly after ELCA (33.2±7.8) and after stent placement (22.8±7.1) than preoperative level (49.7±13.0) (both P<0.001). The minimum stent area was (5.53±1.36)mm², and the stent expansion rate was (90.0±4.3)%. Perforation, no reflow, type Ⅳa myocardial infarction and other complications were not observed. However, postoperative high-sensitivity troponin level was significantly increased ((67.937±33.839)ng/L vs. (5.316±3.105)ng/L, P<0.001). Conclusion: ELCA is safe and effective in the treatment of SVG lesions and could improve microcirculation and ensure full expansion of stent.
Male ; Humans ; Aged ; Prospective Studies ; Percutaneous Coronary Intervention ; Lasers, Excimer/therapeutic use* ; Saphenous Vein/transplantation* ; Constriction, Pathologic ; Atherectomy, Coronary/methods* ; Myocardial Infarction ; Coronary Angiography ; Stents ; Treatment Outcome

OBJECTIVE: To retrospectively analyze the efficacy and complications of our institution's modified nonmyeloablative allogeneic hematopoietic stem cell transplantation (NST) in treating intermediate-risk acute myeloid leukemia (AML) - first complete remission (CR1) and prognostic factors. METHODS: Clinical data of 50 intermediate-risk AML-CR1 patients who underwent matched related NST at the Fifth Medical Center of Chinese People's Liberation Army General Hospital from August 2004 to April 2021 were collected, the hematopoietic recovery, donor engraftment and complications were observed, and overall survival (OS) rate, leukemia-free survival (LFS) rate, treatment-related mortality (TRM), and cumulative relapse rate were calculated. Statistical analysis of factors affecting prognosis was also preformed. RESULTS: The median times for neutrophil and platelet recovery after transplantation were 10 (6-16) and 13 (6-33) days, respectively. One month after transplantation, 22 patients (44%) achieved full donor chimerism (FDC), and 22 patients (44%) achieved mixed chimerism (MC), among whom 18 cases gradually transited to FDC during 1-11 months, 4 cases maintained MC status. The overall incidence of acute graft-versus-host disease (aGVHD) was 36%, with a rate of 18% for grade II-IV aGVHD and a median onset time of 45 (20-70) days after transplantation. The overall incidence of chronic GVHD (cGVHD) was 34%, with 20% and 14% of patients having limited or extensive cGVHD, respectively. The incidence rates of infections, interstitial pneumonia, and hemorrhagic cystitis were 30%, 10%, and 16%, respectively. The 5-year OS rate, LFS rate, TRM, and cumulative relapse rate were 68%, 64%, 16%, and 20%, respectively. The increase of the number of CD34⁺ cells infused had shortened the recovery time for neutrophils and platelets (r =0.563, r =0.350). The number of CD34⁺ cells infused significantly influenced the occurrence of extensive cGVHD (OR =1.36, 95%CI : 1.06-1.84, P =0.024). CONCLUSION Modified NST is effective in treating intermediate-risk AML-CR1 patients, however, further expansion of sample size is needed to study prognostic factors.
Humans ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Leukemia, Myeloid, Acute/complications* ; Prognosis ; Recurrence ; Retrospective Studies

OBJECTIVE: To retrospectively analyze the laborotary test results and clinical data of 31 patients with mixed phenotype acute leukemia (MPAL) in order to summarize and discuss the biological characteristics, curative effect, and prognosis of each subtype of MPAL based on immunophenotype results. METHODS: MPAL patients diagnosed and treated in our hospital from July 2013 to January 2019 were selected to analyze the data of cell morphology, immunophenotyping, cytogenetics, molecular biology (MICM), and routine blood at initial diagnosis. Follow-up was carried out until the last discharge time. RESULTS: Among 31 patients, there were 19 males and 12 females, with a median age of 41(12-76) years old. According to the results of immunophenotyping and EGIL score, there were 16 cases of myeloid-T lymphoid mixed phenotype (myeloid-T group), 9 cases of myeloid-B lymphoid mixed phenotype (myeloid-B group), 5 cases of T-B lymphoid mixed phenotype (T-B group), and 1 case of myeloid-T-B lymphoid mixed phenotype. Compared between different subtypes, the antigen expression characteristics were the highest positive rate and expression rate of HLA-DR in myeloid-B group, and the positive rate of CD2 in T-B group was significantly higher than that in the myeloid-T group. Meanwhile, the expression rates of CD7 and cCD3 (cytoplasmic CD3) in T-B group were higher than those in myeloid-T group, and cCD79a was positive in all cases of myeloid-B group and T-B group. The median WBC of T-B group was 81.92×10⁹/L, which was significantly higher than that of the other two groups (P<0.05). The quantitative results of WT1 were higher than 10^-4 in 92.6% of the patients, and the WT1 expression level in myeloid-B group was significantly lower than the other two groups (P<0.01). Among the 9 patients with myeloid-B mixed phenotype, 5 cases showed BCR-ABL positive. Among 28 patients followed up, 21 cases achieved complete remission (CR), the median time to first obtain CR was 32.5(9-75) days, and the median follow-up time was 16 months (range from 21 days to 6 years). The CR rate and median overall survival (OS) time in myeloid-B group were 88.9% and 40 months, which were higher than the other two groups. The CR rate and 3-year OS rate in T-B group were relatively lower (50.0%, 0). CONCLUSION WT1 gene is highly expressed in patients with MPAL, and each subgroup of MPAL based on immuophenotype has its unique antigen expression characteristics. Compared with myeloid-T group and T-B group, myeloid-B group can acquire higher remission rate and have better prognosis.
Acute Disease ; Female ; HLA-DR Antigens ; Humans ; Immunophenotyping ; Leukemia ; Male ; Phenotype ; Prognosis ; Retrospective Studies

Objective:To explore the influence of intensive analgesia on the incidence of post-traumatic stress disorder (PTSD) in acute trauma patients, and to develop new ideas for the prevention and treatment of PTSD.Methods:From January 2018 to November 2019, a prospective study was conducted on trauma patients who visited the Emergency Center of Affiliated Hospital of Xuzhou Medical University and met the enrollment criteria. The patients were divided into the intensive analgesia group (< 4) and non-intensive analgesia group (≥ 4) according to the mean pain score in 30 days. The epidemiological data, trauma-related parameters, analgesic schemes, VAS score, PCL-5 score, HADS score and incidence of PTSD of enrolled patients were collected. Appropriate statistical methods were used to analyze differences among the indicators between the two groups.Results:Eighty-four acute trauma cases were included in the study, 39 cases in the intensive analgesia group and 45 in the non-intensive analgesia group. There was no significant difference in baseline data between the two groups (all P>0.05). The incidence rate of PTSD and PCL-5 score of patients in the intensive analgesia group were all significantly lower than those in the non-intensive analgesia group in 1 month after the trauma (all P< 0.05). The HADS anxiety and depression scores of patients in the intensive analgesic group were significantly lower than those in the non-intensive analgesic group (all P< 0.05). All the analgesics were converted into the dosage of dezocine for comparison. The total dosage of analgesics (dezocine) used in patients of the intensive analgesia group was significantly higher than that in the non-intensive analgesia group within 30 days after injury ( P< 0.05). Conclusion:In the acute trauma patients, intensive analgesia after trauma can significantly reduce the incidence of PTSD as well as improve anxiety and depression symptoms.

We explored the pharmacodynamic material basis and network regulatory mechanism of Fufang Yuxingcao Mixture (FYM) for the treatment of fever and inflammation. Targets of the 25 compounds in FYM were predicted according to the reverse pharmacophore method and TCMSP, UniProt database. Gene ontology (GO) function enrichment and pathway analysis of the targets was analyzed by Omicsbean software and the Kyoto Gene and Genome Encyclopedia (KEGG) database. A "compound-target-pathway-pharmacological action-effect" network was established with Cytoscape 3.6.1 software. The lipopolysaccharide (LPS)-induced RAW264.7 cell inflammation model was used to verify the anti-inflammatory effects of FYM and its 10 important components. The network pharmacology experiment showed that 25 compounds affected 97 pathways through 211 targets, of which 15 key targets [including RAC-alpha serine/threonine-protein kinase (AKT1), insulin (INS), vascular endothelial growth factor A (VEGFA), interleukin-6 (IL-6), cellular tumor antigen p53 (TP53), tumor necrosis factor (TNF), transcription factor AP-1 (JUN), caspase-3 (CASP3), matrix metalloproteinase-9 (MMP9), interleukin-8 (IL-8), prostaglandin G/H synthase 2 (PTGS2), proto-oncogene c-Fos (FOS), tyrosine-protein kinase SRC (SRC), c-Jun N-terminal kinase 1 (MAPK8), estrogen receptor 1 (ESR1)] and 46 pathways (including NF-kappa B signaling pathway, Toll-like receptor signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, arachidonic acid metabolism, cAMP signaling pathway, T cell receptor signaling pathway, calcium signaling pathway, inflammatory mediator regulation of TRP channels, chemokine signaling pathway, Th1 and Th2 cell differentiation, natural killer cell mediated cytotoxicity, etc.) were related to anti-inflammatory, antipyretic, immune regulation, and analgesia. In vitro cell experiments showed that FYM and the 10 components (including isoquercitrin, luteoloside, baicalein, wogonin, wogonoside, phillyrin, forsythoside A, chlorogenic acid, isochlorogenic acid A, and sweroside) could significantly reduce the expression of nitric oxide (NO), TNF-α and IL-6 in cell supernatants, indicating that the above 10 components may be the key pharmacodynamic material basis of FYM.

Objective:To investigate the 2 years’ efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation.Methods:From July 2015 to June 2020, 18-75 years old patients with moderate to high-risk non muscle invasive bladder cancer (NMIBC) confirmed by pathological examination were involved. The ECOG score was 0-2. Exclusion criteria included ①immune deficiency or impairment (such as AIDS), using immunosuppressive drugs or radiotherapy, suspected allergic to BCG or epirubicin or excipients of the two drugs, fever or acute infectious diseases including active tuberculosis or receiving anti tuberculosis treatment, with severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease; ②combined with other urogenital system tumors or other organ tumors; ③combined with muscle invasive bladder urothelial carcinoma (≥T 2); ④undergoing chemotherapy, radiotherapy or immunotherapy within 4 weeks (immediate instillation after surgery not included); ⑤ pregnant or lactating women; ⑥ comfirmed or suspected bladder perforation; ⑦gross hematuria; ⑧cystitis with severe bladder irritation that may affect the evaluation; ⑨participat in other clinical trials within 3 months; ⑩alcohol or drug addiction; ?any risk factors that may increasing the risk of patients. Epirubicin 50 mg was irrigated immediately after the operation(TURBT or laser resection). The patients were randomly divided into BCG15 group, BCG19 group and epirubicin group by the ratio of 2∶2∶1, and the patients were maintained intravescical instillation for 1 year. The recurrence and adverse events of the three groups were compared. Univariate and multivariate analysis was performed to predict the risk factors of BCG irrigated therapy failure. Result:By June 15, 2020, the median follow-up duration was 22.1 months(12.1, 32.3), and there was no statistical difference between the groups ( P=0.9024). There were 274 patients enrolled in BCG19 group, 277 patients enrolled in BCG15 group and 130 patients enrolled in the epirubicin group. The drop-off rate was 16.6%(113 cases)and made no difference between groups( P=0.6222). There were no significant difference in age, gender, BMI, or ECOG score( P>0.05). During the follow-up, 116 cases was detected recurrence or progression. The recurrence rate of the three groups was 14.2% and 14.8% in BCG19 group and BCG15 group, and 27.7% in the epirubicin group. There was no difference in recurrence rate between BCG19 and BCG15 group( P=0.9464). The recurrence rate of BCG19 group was lower than that of the epirubicin group ( P=0.0017). The recurrence rate of BCG15 group was lower than that of the epirubicin group ( P=0.0020). There was no difference in the cumulative recurrence free survival rate between BCG19 and BCG15 group (95% CI0.57-1.46, P=0.7173). The cumulative recurrence free survival rate of BCG 19 group was better than that of the epirubicin group( HR=0.439, 95% CI0.26-0.74, P=0.0006), and the cumulative recurrence free survival rate of BCG15 group was better than that of the epirubicin group ( HR=0.448, 95% CI0.29-0.80, P=0.0021). The total incidence of adverse events in 19 BCG19, BCG15 and epirubicin group were 74.5%, 72.6% and 69.8% respectively. There was no difference in the incidence of adverse events between BCG19 and BCG15 group( P=0.6153). The incidence of adverse events in epirubicin group was lower than that of BCG19( P=0.0051) and BCG15( P=0.0167) groups.There was no significant difference in the incidence of serious adverse events (SAE) among the three groups ( P=0.5064). Log rank test univariate analysis and Cox risk regression model multivariate analysis showed that the history of bladder cancer recurrence( HR=6.397, 95% CI1.95-20.94, P=0.0001)was independent risk factor for BCG irrigation failure. Conclusions:The 2 years’ efficacy of intravesical instillation of domestic BCG is better than than of epirubicin with good tolerance and safety. There is no difference between BCG19 and BCG15 group. BCG doesn’t increase SAE compared with epirubicin. Recurrence status was an independent prognostic factor regarding recurrence-free survival.

Objective:To investigate the effect of post-traumatic pain on post-traumatic stress disorder (PTSD).Methods:A prospective trial was conducted with the recruitment of patients referred to the Emergency Center of Affiliated Hospital of Xuzhou Medical University for acute trauma from January 2018 to June 2019, with the exclusion criteria: age < 18 years, severe eye injury, severe craniocerebral injury and other critical conditions. The clinical data and written informed consent were collected at admission, the post-traumatic pain was assessed by VAS scores and the trauma severity was assessed by ISS score. APACHEⅡ score were evaluated within 24 h after admission. One month after trauma, patients with history of mental illness, or history of major psychogenic trauma within one year or drug addiction were further excluded. Accordingly, 64 eligible patients were evaluated by VAS, and the PCL-5 scale was used to evaluated their PTSD symptoms. The patients were divided into the PTSD group and non-PTSD group according to PCL-5 score≥ 38, and the difference between the two groups in post-traumatic VAS scores was compared. Logistic regression analysis was used to analyze the risk factors of PTSD. Spearman correlation analysis was adopted to establish the correlation between VAS score at admission and PCL-5 score at one month after trauma. The receiver operator characteristic (ROC) curve was used to analyze the predictive value of traumatic pain intensity for PTSD onset.Results:Sixty-four patients were selected and defined as the PTSD group ( n=19) and non-PTSD group ( n=45). The VAS score at admission was significantly higher in the PTSD group than that in the non-PTSD group ( P=0.006). There was no significant difference in VAS scores and VAS variations at 1 month, and in ISS scores at admission and APACHEⅡ scores within 24 h after admission between the two groups. Traumatic pain was an independent risk factor for PTSD ( P=0.043). VAS score at admission was positively correlated with PCL-5 score at 1 month post-traumatically ( r=0.355, P=0.004). In addition, ROC curve analysis showed that VAS score > 8 at admission had predictive value for PTSD (sensitivity=100%, specificity=33%, P=0.000 2). Conclusions:Post-traumatic severe pain is an independent risk factor for PTSD, which requires prompt medical intervention.