Inflammatory bowel disease(IBD)is a chronic and recurrent intestinal disease,and has become a major global health issue.Individuals with IBD face an elevated risk of developing colorectal cancer(CRC),and recent studies have indicated that mitochondrial dysfunction plays a pivotal role in the pathogenesis of both IBD and CRC.This review covers the pathogenesis of IBD and CRC,focusing on mitochondrial dysfunction,and explores pharmacological targets and strategies for addressing both conditions by modulating mitochondrial function.Additionally,recent advancements in the phar-macological modulation of mitochondrial dysfunction for treating IBD and CRC,encompassing mitochondrial damage,release of mitochondrial DNA(mtDNA),and impairment of mitophagy,are thoroughly summarized.The review also provides a systematic overview of natural compounds(such as flavonoids,alkaloids,and diterpenoids),Chinese medicines,and intestinal microbiota,which can alleviate IBD and attenuate the progression of CRC by modulating mitochondrial function.In the future,it will be imperative to develop more practical methodologies for real-time monitoring and accurate detection of mitochondrial function,which will greatly aid scientists in identifying more effective agents for treating IBD and CRC through modulation of mitochondrial function.

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal disease, and has become a major global health issue. Individuals with IBD face an elevated risk of developing colorectal cancer (CRC), and recent studies have indicated that mitochondrial dysfunction plays a pivotal role in the pathogenesis of both IBD and CRC. This review covers the pathogenesis of IBD and CRC, focusing on mitochondrial dysfunction, and explores pharmacological targets and strategies for addressing both conditions by modulating mitochondrial function. Additionally, recent advancements in the pharmacological modulation of mitochondrial dysfunction for treating IBD and CRC, encompassing mitochondrial damage, release of mitochondrial DNA (mtDNA), and impairment of mitophagy, are thoroughly summarized. The review also provides a systematic overview of natural compounds (such as flavonoids, alkaloids, and diterpenoids), Chinese medicines, and intestinal microbiota, which can alleviate IBD and attenuate the progression of CRC by modulating mitochondrial function. In the future, it will be imperative to develop more practical methodologies for real-time monitoring and accurate detection of mitochondrial function, which will greatly aid scientists in identifying more effective agents for treating IBD and CRC through modulation of mitochondrial function.

Objective·To identify relevant biomarkers for patients with coronavirus disease 2019-associated kidney injury(COVID-19-associated KI)and explore the mechanisms underlying the involvement of severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)proteins in infection-related KI by affecting the interactions between renal cells and macrophages.Methods·A retrospective analysis was conducted on the clinical characteristics of COVID-19 patients with KI treated in Shanghai Ninth,People's,hospital from December 2022 to February 2023.Serum levels of inflammatory factors and chemokines were measured by using enzyme-linked immunosorbent assay(ELISA).In vitro,human macrophage cell line THP-1 cells were stimulated with recombinant S1 subunit protein derived from SARS-CoV-2 spike protein.The cells and culture supernatants were collected to detect the levels of inflammatory factors and chemokines by using quantitative real-time PCR(qRT-PCR)and ELISA.Conditioned medium was prepared from the cell culture supernatants of S1-stimulated THP-1 cells and used to stimulate human renal epithelial cells(HK-2)in vitro to assess cytokine secretion.Antibody blocking experiments were performed to analyze the effects of the conditioned medium on the production of cytokines in HK-2 cells.Results·Among 39 patients with COVID-19,8(20.50%)had creatinine levels above the reference interval,which indicated the occurrence of KI.The levels of peripheral tumor necrosis factor-α(TNF-α)in the COVID-19 patient with KI group[(18.33±8.20)pg/mL]were significantly higher than those in the non-KI group[(11.88±6.50)pg/mL](P=0.015).In vitro assay has shown that S1-spike protein stimulation promoted the level of gene transcription and production of TNF-α,interleukin-1β(IL-1β)and chemokine C-X-C motif ligand 10(CXCL10)in THP-1 macrophage cells(P＜0.001).Furthermore,the conditioned medium from S1-stimulated THP-1 cells promoted the secretion of TNF-α,IL-1β and CXCL10 by HK-2 cells(P=0.005).When anti-TNF-α antibody(Infliximab)was used to block TNF-α in the culture supernatants from S1-stimulated THP-1 cells,the secretion level of TNF-α by HK-2 cells decreased dramatically(P＜0.001).Conclusion·TNF-α levels increase significantly in COVID-19 patients with KI,implying the significance of TNF-α in the occurrence of COVID-19-associated KI.In vitro experiments confirm that the S1 protein induces TNF-α secretion from THP-1 cells,leading to increased inflammatory responses in renal cells,which may contribute to the development of COVID-19-associated KI.Therefore,targeting TNF-α may become an alternative strategy to reduce the occurrence of COVID-19-associated KI.

Objective·To identify relevant biomarkers for patients with coronavirus disease 2019-associated kidney injury(COVID-19-associated KI)and explore the mechanisms underlying the involvement of severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)proteins in infection-related KI by affecting the interactions between renal cells and macrophages.Methods·A retrospective analysis was conducted on the clinical characteristics of COVID-19 patients with KI treated in Shanghai Ninth,People's,hospital from December 2022 to February 2023.Serum levels of inflammatory factors and chemokines were measured by using enzyme-linked immunosorbent assay(ELISA).In vitro,human macrophage cell line THP-1 cells were stimulated with recombinant S1 subunit protein derived from SARS-CoV-2 spike protein.The cells and culture supernatants were collected to detect the levels of inflammatory factors and chemokines by using quantitative real-time PCR(qRT-PCR)and ELISA.Conditioned medium was prepared from the cell culture supernatants of S1-stimulated THP-1 cells and used to stimulate human renal epithelial cells(HK-2)in vitro to assess cytokine secretion.Antibody blocking experiments were performed to analyze the effects of the conditioned medium on the production of cytokines in HK-2 cells.Results·Among 39 patients with COVID-19,8(20.50%)had creatinine levels above the reference interval,which indicated the occurrence of KI.The levels of peripheral tumor necrosis factor-α(TNF-α)in the COVID-19 patient with KI group[(18.33±8.20)pg/mL]were significantly higher than those in the non-KI group[(11.88±6.50)pg/mL](P=0.015).In vitro assay has shown that S1-spike protein stimulation promoted the level of gene transcription and production of TNF-α,interleukin-1β(IL-1β)and chemokine C-X-C motif ligand 10(CXCL10)in THP-1 macrophage cells(P＜0.001).Furthermore,the conditioned medium from S1-stimulated THP-1 cells promoted the secretion of TNF-α,IL-1β and CXCL10 by HK-2 cells(P=0.005).When anti-TNF-α antibody(Infliximab)was used to block TNF-α in the culture supernatants from S1-stimulated THP-1 cells,the secretion level of TNF-α by HK-2 cells decreased dramatically(P＜0.001).Conclusion·TNF-α levels increase significantly in COVID-19 patients with KI,implying the significance of TNF-α in the occurrence of COVID-19-associated KI.In vitro experiments confirm that the S1 protein induces TNF-α secretion from THP-1 cells,leading to increased inflammatory responses in renal cells,which may contribute to the development of COVID-19-associated KI.Therefore,targeting TNF-α may become an alternative strategy to reduce the occurrence of COVID-19-associated KI.

Objective To observe the effect of Xinmailong injection on microcirculation in patients with septic shock,so as to understand the application effect and value of Xinmailong injection in patients with septic shock.Methods A total of 82 patients with septic shock treated in the intensive care unit of our hospital were selected as the research objects and randomly divided into two groups.41 patients in the control group were treated with conventional septic shock cluster therapy,and 41 patients in the treatment group were treated with Xinmailong injection on the basis of cluster therapy in the control group.Then hemodynamic parameters(HR,CVP,CO,MAP,SVR),hemorheology(whole blood reducing viscosity,hematocrit,fibrinogen,platelet aggregation rate),microcirculation perfusion indexes(oxygenation index,blood lactate level,SCVO2,Pcv-aCO2)and 28-day survival rate were detected and compared between the two groups before and after treatment.Results Before treatment,there were no significant differences in hemodynamic parameters,blood rheology and microcirculation perfusion indexes between the two groups(P>0.05).After treatment,the above test results of the two groups were signifi-cantly improved,and the test results of the treatment group were significantly better than those of the control group,and the 28-day survival rate was also better than that of the control group.The differences were statistically significant(P<0.05).Conclusion Xinmailong injection can significantly improve the hemodynamic parameters,blood rheology and microcirculation perfusion indexes,and improve the 28-day survival rate of patients with sepsis.It has a positive clinical effect in the treatment of septic shock patients.

Abdomen/diagnostic imaging* ; Artificial Intelligence ; Body Composition ; Magnetic Resonance Imaging ; Practice Guidelines as Topic

Objective:To investigate the effect of thrombus burden on the clinical outcome of endovascular recanalization in large vessel occlusive stroke.Methods:Patients with acute anterior circulation occlusion who underwent endovascular treatment within 24 hours after onset in Zhengzhou University People′s Hospital from January 2018 to December 2019 were retrospectively collected. According to the clot burden score (CBS) of DSA, total objectives were divided into CBS≥6 group (24 cases) and CBS<6 group (38 cases). Clinical data of the two groups were collected and the modified Rankin scale (mRS) was used to evaluate the clinical outcome at 90 days after surgery. Independent sample t-test, Wilcoxon rank sum test and χ 2 test were used to compare the clinical data between the two groups. Independent risk factors affecting the clinical outcome were analyzed by binary logistic regression. Results:There were no statistically significant differences in basic demographic data, stroke risk factors and other factors between the CBS≥6 group and CBS<6 group ( P>0.05).The proportion of using tirofiban after surgery in the CBS≥6 group (63.2%, 24/38) was lower than that in the CBS<6 group (87.5%, 21/24) (χ2=4.380, P=0.044). The discharge NIHSS score of the CBS≥6 group was [5.0 (3.3, 7.8) points] lower than CBS<6 group [8.5 (1.8, 14.5) points] ( Z=5.221, P=0.022). The proportion of postoperative mRS 0-2 was (91.7%, 22/24) in the CBS≥6 group higher than CBS<6 group(39.5%, 15/38) (χ2=20.486, P=0.001), there were no statistically significant differences between the two groups ( P<0.05). The results of binary logistics regression analysis showed the CBS groups (OR=0.042, 95%CI 0.007-0.244 , P=0.001) was an independent risk factor affecting good outcome. Subgroup analysis of whether tirofiban was used or not showed there was no statistically significant difference in clinical prognosis between the two groups ( P>0.05). Conclusions:The clinical outcome of CBS≥6 group is significantly better than that of CBS<6 group, and patients with small thrombus burden are more likely to get a good clinical outcome of 90 days.

Objective:To investigate the safety and efficacy of endovascular treatment in acute anterior circulation massive cerebral infarction and its prognostic factors.Methods:A retrospective analysis was performed on clinical data of 34 patients with acute anterior circulatory massive cerebral infarction who received intravascular treatment in our hospital from February 2018 to December 2019. The perioperative hemorrhage rate and mortality rate were analyzed in these patients. Modified Rankin scale (mRS) scores were taken as the evaluation standard in the prognoses of these patients during the 90 d of follow up, and the influencing factors affecting the prognoses of patients with massive cerebral infarction were analyzed.Results:The operation was successful in 30 patients (88.2%); the operation time was (97.41±54.58) min, and the number of thrombolysis was (1.91±0.75) times. Distal embolization occurred in 4 patients (11.8%); there were 3 patients with non-symptomatic hemorrhage (8.8%) and 3 patients with symptomatic hemorrhage (8.8%). Cerebral hernia occurred in 7 patients (20.6%); there were 5 deaths (14.4%). During the 90 d of follow up, 13 patients (38.2%) had good prognosis, and 21 (61.8%) had poor prognosis; there were statistically significant differences in NIHSS scores at admission, infarction locations in diffusion weighted imaging, vascular occlusion locations in DSA, pecentages of patients accepted preoperative intravenous thrombolysis and patients with cerebral hernia between the two groups ( P<0.05). NIHSS scores at admission ( OR=0.817, 95% CI: 0.682-0.980, P=0.029), thrombus load scale scores ( OR=5.981, 95%CI: 1.827-19.575, P=0.003), vascular occlusion locations in DSA ( OR=0.031, 95% CI: 0.003-0.311, P=0.003) and pecentage of patients accepted preoperative intravenous thrombolysis ( OR=0.092, 95% CI: 0.010-0.838, P=0.034) were independent factors influencing the prognoses of emergency intravascular treatment. Conclusions:Endovascular recanalization can achieve a relatively good prognosis in patients with massive cerebral infarction. Patients with low NIHSS scores, high thrombotic load scale scores, and middle cerebral artery occlusion, and patients accepted direct intravascular treatment have relatively good prognosis.

Objective:To explore the characteristics of high-density sign of flat-panel CT (FDCT) after endovascular treatment in patients with acute ischemic stroke (AIS) in the anterior circulation of large vessels and their relation with hemorrhagic transformation.Methods:Seventy-eight patients with AIS in the anterior circulation of large vessels accepted endovascular treatment in our hospital from March 2018 to June 2019 were chosen in our study. All patients underwent FDCT, and they were grouped according to the presence of local high-density sign and occurrence of hemorrhagic transformation. The baseline and clinical data of patients from high-density sign group and non-high-density sign group, and from hemorrhagic transformation group and non-hemorrhagic transformation group were compared and analyzed. The correlation between high-density sign and hemorrhagic transformation was analyzed. The morphological characteristics and distribution of FDCT high-density sign in patients from high-density sign group were analyzed, and univariate and multivariate Logistic regression analyses were used to screen the influencing factors for post-operative hemorrhagic transformation in patients from the high-density sign group.Results:(1) The incidence of high-density sign in these patients after endovascular treatment was 41.0% (32/78); as compared with patients in the non-high-density sign group, patients in the high-density sign group had significantly higher rate of hemorrhagic transformation (6.5% vs. 53.1%, P<0.05) and significantly higher 3-month modified Rankin scale (mRS) scores (2.0 [1.0, 3.0] vs. 3.9 [3.0, 5.3], P<0.05). (2) The incidence of hemorrhagic transformation after endovascular treatment was 25.6% (20/78); as compared with those in the non-hemorrhagic transformation group, patients in the hemorrhage transformation group had statistically higher incidence of high-density sign in FDCT (31% vs. 70%, P<0.05); multivariate Logistic regression analysis showed that FDCT high density sign was an independent risk factor for hemorrhage transformation after endovascular treatment ( OR=1.823, 95%CI: 1.125-2.358, P=0.000). (3) In the 32 patients with FDCT high-density sign, 4 (12.5%), 13 (40.6%) and 7 (21.9%) had high-density sign in the cortex and subcortex, basal ganglia, and subarachnoid space, whose hemorrhagic transformation incidences were 75% (3/4), 53.8% (7/13), and 57.1% (4/7), respectively, and mean 3-month mRS scores were 4.5, 3.0 and 4.0, respectively; another 8 patients (25%) had endovascular FDCT high-density sign, whose hemorrhagic transformation incidence was 87.5% (7/8), and 3-month mRS scores were ≥4. (4) Multivariate Logistic regression analysis showed that the vascular opening time ≤6 h was a protective factor for hemorrhage transformation in patients with FDCT high-density sign ( OR=0.687, 95%CI: 0.193-0.936, P=0.044). Conclusions:In patients with AIS in the anterior circulation of large vessels accepted endovascular treatment, FDCT high-density sign indicates high risk of hemorrhage transformation and poor prognosis, especially in patients having high-density sign in the cerebral cortex, subcortical area and intravascular area. Minimizing the vascular opening time may reduce the risk of hemorrhagic transformation in patients with FDCT high-density sign.

Objective To investigate the safety of endovascular thrombectomy in acute ischemic stroke patients with pre-existing intracranial aneurysms. Methods Seven patients with acute ischemic stroke combined with intracranial aneurysms, admitted to and received endovascular treatment in our hospital from January 2014 to December 2016, were chosen. The clinical data and safety were analyzed retrospectively. Results All patients with pre-existing intracranial aneurysms suffered acute large artery occlusion achieved successful endovascular re-canalization, and one patient suffered subarachnoid hemorrhage due to the rupture of aneurysm during the procedure. Three patients had grading 2b of Thrombolysis in Cerebral Infarction (TICI), and 4 had grading 3 of TICI. Four patients had 0-2 scores of modified Rankin Scale (mRS), one had 3 scores, and two died. Conclusion Endovascular thrombectomy in acute ischemic stroke patients with pre-existing intracranial aneurysms is safe.