Objective To study the protective effect of lipoxin A4(LXA4)against sepsis-induced acute kidney in-jury(SAKI)in rats and its effect on the expression of toll-like receptor 4(TLR4),myeloid differentiation factor88(MyD88),nuclear factor kappa B(NF-κB)in the kidney.Methods Forty male specific pathogen-free C57BL/6J mice were randomly divided into SAKI group,SAKI+LXA4 group,sham procedure group,sham procedure+LXA4 group.The mice in SAKI group and SAKI+LXA4 group were given cecum ligation and puncture(CLP)to establish SAKI animal models.The mice in SAKI+LXA4 group and sham procedure+LXA4 group were given LXA4(40 ng/kg)with intraperitoneal injection 30 mins after CLP.All mice were sacrificed at the 24th hour after CLP to collect serum,urine and kidney tissues.The enzyme linked immunosorbent assay(ELISA)was used to test the serum creat-inine(Scr),blood urea nitrogen(Bun),interleukin-1 β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α)and urine neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule 1(KIM-1)levels of mice.The pathologi-cal changes were examined through hematoxylin-eosin(HE)staining and Periodic Acid-Schiff(PAS)staining.And the mRNA levels of TLR4,MyD88,NF-κB p65 were detected through real-time PCR(RT-PCR);the expression lev-els of TLR4,MyD88,NF-κB p65,phospho-NF-KB p65(p-NF-KB p65)were detected through immunohistochemistry(IHC)and Western blot assay.Results ELISA showed that the values of Scr,Bun,IL-1 β,IL-6,TNF-α,NGAL,KIM-1 in SAKI group were higher than those in SAKI+LXA4 group(P＜0.05),and there were no significant differences in Scr,Bun,IL-1 β,IL-6,TNF-α,NGAL,KIM-1 between sham procedure group and sham procedure+LXA4 group.HE and PAS staining showed that SAKI group had severer pathological changes than SAKI+LXA4 group in the kidney structure(P＜0.05),while pathological structures of the kidney were normal in sham proce-dure group and sham procedure+LXA4 group.RT-PCR showed that the mRNA levels of TLR4,MyD88,N F-κB p65 in SAKI group,SAKI+LXA4 group were higher than sham procedure group and sham procedure+LXA4 group(P＜0.05);the mRNA levels of TLR4,MyD88,NF-κB p65 in SAKI group were higher than SAKI+LXA4 group(P＜0.05);The results of IHC,Western blot assay were as follows:The expression levels of TLR4,MyD88,NF-κB p65,p-NF-κB p65 in SAKI group,SAKI+LXA4 group were higher than sham procedure group and sham procedure+LXA4 group(P＜0.05);the expression levels of TLR4,MyD88,NF-κB p65,p-NF-κB p65 in SAKI group were higher than SAKI+LXA4 group(P＜0.05).Conclusion TLR4/MyD88/NF-KB pathway plays an important role in the occurrence and development of SAKI,and LXA4 may reduce SAKI by inhibiting TLR4/MyD88/NF-κB sig-naling pathway.

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.

Alzheimer's disease (AD) is associated with the impairment of white matter (WM) tracts. The current study aimed to verify the utility of WM as the neuroimaging marker of AD with multisite diffusion tensor imaging datasets [321 patients with AD, 265 patients with mild cognitive impairment (MCI), 279 normal controls (NC)], a unified pipeline, and independent site cross-validation. Automated fiber quantification was used to extract diffusion profiles along tracts. Random-effects meta-analyses showed a reproducible degeneration pattern in which fractional anisotropy significantly decreased in the AD and MCI groups compared with NC. Machine learning models using tract-based features showed good generalizability among independent site cross-validation. The diffusion metrics of the altered regions and the AD probability predicted by the models were highly correlated with cognitive ability in the AD and MCI groups. We highlighted the reproducibility and generalizability of the degeneration pattern of WM tracts in AD.
Humans ; White Matter/diagnostic imaging* ; Diffusion Tensor Imaging/methods* ; Alzheimer Disease/complications* ; Reproducibility of Results ; Cognition ; Cognitive Dysfunction/complications* ; Brain/diagnostic imaging*

Objective:This paper aimed to explore the problems and solutions in the management of Investigator-Initiated Trail (IIT) in medical institutions, to provide suggestions particularly in the absence of relevant high-level policy support.Methods:By combining literature review with working practice experiences, this paper analyzed the current situation of IIT’s management and the rationale, put forward suggestions.Results:IIT related problems identified including as the responsible entities of the management, research topics selection, protocol design, continuity, research team construction, ethical review and the cultivation of research management personnel. The centralized management will help the standardized management of such projects, the training of investigators and team building, the review awareness strengthening of the ethics committee, improvement of management ability.Conclusions:IIT plays an important role in promoting the development of medical scientific research. Medical institutions should integrate resources, provide platforms, train investigators assure the quality of IITs.

Objective To investigate the effect of ulinastatin on postoperative clinical outcomes in pa-tients undergoing elective laparoscopic colectomy. Methods 454 patients underwent elective laparoscopic colecto-my from January 2015 to September 2017 were included in this retrospective study. Patients were divided into 2 groups:ulinastatin group and control group. Propensity score matching was applied to balance the preoperative baseline differences between 2 groups. 155 patients in each group were successfully matched. Mixed linear model was used to exam the effect of ulinastatin on various clinical indicators within 3 days after the surgery,including in-flammation indicators(white blood cell counts,C reactive protein),liver function indicators(alanine transami-nase,aspartate transaminase,total bilirubin),renal function indicators(serum creatinine,blood urea nitrogen). Postoperative hospital length of stay was compared between 2 groups using student's t-test. Results Ulinastatin group showed significantly reduced postoperative white blood cell count and ? reactive protein level (P = 0.036 and 0.025)compared with the control group. The average mean inhibitory effects were 1.04×109/L and 23.93 mg/L respectively,which was 11.1% and 29.9% lower than that of the control group. Procalcitonin,transaminases,total bilirubin,serum creatinine,blood urea nitrogen levels and postoperative hospital length of stay showed no signifi-cant difference between the two groups(P > 0.05). Conclusion Ulinastatin can significantly reduce the level of inflammation response after laparoscopic colectomy,which is beneficial to the fast recovery.

OBJECTIVETo investigate the effects of different doses of propofol on pulmonary metastasis of intravenous injected MADB106 tumor cells and the expression of E-cadherin and β-catenin in the metastatic tumor tissue in rats.

METHODSForty Fischer 344 male rats were randomly divided into 4 groups (n=10) for intravenous administration of normal saline, intralipid, or propofol at 30 or 50 mg/kg via the femoral vein. One hour after the infusion, MADB106 tumor cells (2×10(5)) were injected intravenously in the rats. Three weeks later, pulmonary metastasis tumor foci and metastatic inhibitory rate were observed and the expression of E-cadherin and β-catenin in the metastatic tumor tissue were detected by immunohistochemistry.

RESULTSCompared with the normal saline group, intralipid group showed no significant differences in the number of metastatic tumor foci in the lungs or E-cadherin and β-catenin expressions (P>0.05), which were all significantly lowered in the two propofol groups (P<0.05 or 0.01). The dose of propofol was inversely correlated with the number of metastasis tumor foci (r=-0.879) and expressions of E-cadherin (r=-0.755) and β-catenin (r=-0.693) (P<0.01).

CONCLUSIONPropofol can dose-dependently suppress pulmonary metastasis of intravenous injected MADB106 tumor cells by inhibiting the Wnt/β-catenin pathway and down-regulating E-cadherin and β-catenin expressions in the metastatic tumor tissue.

Animals ; Cadherins ; metabolism ; Dose-Response Relationship, Drug ; Down-Regulation ; Immunohistochemistry ; Injections, Intravenous ; Lung Neoplasms ; drug therapy ; Male ; Neoplasm Metastasis ; drug therapy ; Neoplasm Transplantation ; Propofol ; pharmacology ; Rats ; Rats, Inbred F344 ; beta Catenin ; metabolism

Aged ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Humans ; Lymphoma, Large B-Cell, Diffuse ; Prognosis

Objective To investigate the value of 18F-FDG PET-CT in detection and accurate staging of extranodal non-Hodgkin lymphoma (NHL).Methods The results of PET-CT of 94 patients with NHL were retrospectively analyzed.The consistency of checking out lesions and accurate staging by PET-CT were compared with those by other imaging examination in extranodal NHL.Results 432 lesions were checked out by PET-CT, including 319 (73.8 ％) lymphoid tissues and organs with the average SUVmax of 13.4 (3.4-33.4), and 113 (26.2 ％) extranodal lesions with the average SUVmax of 13.5 (3.1-55.0).The detection consistent rate between CT and PET-CT for lymphoid tissues and lymph organ lesions was 95 ％, while the consistent rate of the extranodal lesions was only 54.9 ％.The detection rates of PET-CT for soft tissue, bone and gastrointestinal lesions were higher than those of CT, but the detection rate for the bone marrow lesion was lower than that for the bone marrow cytology.According to the results of PET-CT, the stages of 29 patients (31.0 ％) were re-adjusted, including up-regulated for 75.9 ％ (22/29) because of high detection rates of PET-CT for soft tissue and skeletal lesions, and down-regulated for 24.1％ (7/29) mainly due to the strong resolution capability of PET-CT for detection of non-neoplastic lymph nodes and spleen increasing or effusion.Conclusion 18F-FDG PET-CT can improve the detection rate of NHL extranodal lesions, especially for diffuse non-mass lesions in bone and soft tissues, which facilitates the accurate lymphoma staging.

Objective To investigate the effects of different doses of propofol on pulmonary metastasis of intravenous injected MADB106 tumor cells and the expression of E-cadherin and β-catenin in the metastatic tumor tissue in rats. Methods Forty Fischer 344 male rats were randomly divided into 4 groups (n=10) for intravenous administration of normal saline, intralipid, or propofol at 30 or 50 mg/kg via the femoral vein. One hour after the infusion, MADB106 tumor cells (2 × 105) were injected intravenously in the rats. Three weeks later, pulmonary metastasis tumor foci and metastatic inhibitory rate were observed and the expression of E-cadherin and β-catenin in the metastatic tumor tissue were detected by immunohistochemistry. Results Compared with the normal saline group, intralipid group showed no significant differences in the number of metastatic tumor foci in the lungs or E-cadherin and β-catenin expressions (P>0.05), which were all significantly lowered in the two propofol groups (P<0.05 or 0.01). The dose of propofol was inversely correlated with the number of metastasis tumor foci (r=-0.879) and expressions of E-cadherin (r=-0.755) and β-catenin (r=-0.693) (P<0.01). Conclusion Propofol can dose-dependently suppress pulmonary metastasis of intravenous injected MADB106 tumor cells by inhibiting the Wnt/β-catenin pathway and down-regulating E-cadherin andβ-catenin expressions in the metastatic tumor tissue.