Coronavirus disease 2019 (COVID-19) is a multi-system disease that can lead to various severe complications. Acute limb ischemia (ALI) has been increasingly recognized as a COVID-19-associated complication that often predicts a poor prognosis. However, the pathophysiology and molecular mechanisms underlying COVID-19-associated ALI remain poorly understood. Hypercoagulability and thrombosis are considered important mechanisms, but we also emphasize the roles of vasospasm, hypoxia, and acidosis in the pathogenesis of the disease. The angiotensin-converting enzyme 2 (ACE2) pathway, inflammation, and platelet activation may be important molecular mechanisms underlying these pathological changes induced by COVID-19. Furthermore, we discuss the hypotheses of risk factors for COVID-19-associated ALI from genetic, age, and gender perspectives based on our analysis of molecular mechanisms. Additionally, we summarize therapeutic approaches such as use of the interleukin-6 (IL-6) blocker tocilizumab, calcium channel blockers, and angiotensin-converting enzyme inhibitors, providing insights for the future treatment of coronavirus-associated limb ischemic diseases.
Humans ; COVID-19/physiopathology* ; Ischemia/etiology* ; SARS-CoV-2 ; Extremities/blood supply* ; Risk Factors ; Interleukin-6/antagonists & inhibitors* ; Acute Disease ; Angiotensin-Converting Enzyme 2

Objective:To explore the diagnostic value of preoperative diffusion weighted imaging (DWI) histogram parameters in the depth of invasion of early rectal cancer.Methods:A total of 180 patients with early rectal cancer admitted to 904th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army from August 2020 to August 2024 were selected as the study objects. Patients were divided into intramucosal cancer group ( n=102) and submucosal cancer group ( n=78) according to the depth of tumor invasion. The general data of the two groups were compared. The intraclass correlation coefficient (ICC) was used to analyze the consistency of DWI histogram parameters extracted by the two radiologists, and the differences between the two groups were compared. Receiver operator characteristic (ROC) curve was used to analyze the predictive value of each parameter to the depth of tumor invasion. Multivariate logistic regression was used to analyze the independent influencing factors of invasion depth, and a predictive model was constructed. The ROC curve was drawn to analyze the predictive value of the model for tumor invasion depth, and the Hosmer-Lemeshow test was used to analyze the goodness of fit of the model. Results:There were statistically significant differences in age ( t=8.15, P<0.001), maximum tumor diameter ( χ2=29.29, P<0.001), endoscopic type ( χ2=20.96, P<0.001), histological type ( χ2=24.93, P<0.001) and differentiation degree ( χ2=73.35, P<0.001) between intramucosal cancer group and submucosal cancer group. The mean, variance, skewness, kurtosis, the 1 st, 10 th, 50 th, 90 th, and 99 th percentiles of the histogram parameters of DWI had good consistency (all ICC>0.75). There were statistically significant differences in the mean ( t=5.69, P<0.001), variance ( t=9.75, P<0.001), skewness ( t=10.88, P<0.001), kurtosis ( t=10.06, P<0.001), the 1 st percentile ( t=3.43, P<0.001), 10 th percentile ( t=3.59, P<0.001), 50 th percentile ( t=9.97, P<0.001), 90 th percentile ( t=4.63, P<0.001), and 99 th percentile ( t=2.44, P=0.016) of the DWI histogram parameters between the intramucosal cancer group and the submucosal cancer group. ROC curve analysis results showed that mean [area under the curve (AUC) =0.77], variance (AUC=0.88), skewness (AUC=0.88), kurtosis (AUC=0.78), 50 th percentile (AUC=0.86) and 90 th percentile (AUC=0.82) had certain diagnostic value for submucous cancer. Multivariate analysis showed that age ( OR=9.98, 95% CI: 1.10-90.70, P=0.041), maximum tumor diameter ( OR=7.36, 95% CI: 1.08-50.23, P=0.042), and differentiation degree ( OR=19.88, 95% CI: 1.21-327.92, P=0.037), variance ( OR=16.24, 95% CI: 2.26-116.68, P=0.006), skewness ( OR=21.13, 95% CI: 2.80-59.61, P=0.003), 1 st percentile ( OR=9.78, 95% CI: 1.17-81.76, P=0.035) were independent factors in predicting tumor invasion depth in patients with early rectal cancer. The predictive model based on the above indicators was logit ( P) =1.51+2.30×age+2.00×maximum tumor diameter+2.99×differentiation degree+2.79×variance+3.05×skewness+ 2.28×the 1 st percentile. ROC curve analysis showed that the predictive model had an AUC of 0.97 (95% CI: 0.95-0.99) for judging the occurrence of submucosal cancer in patients with early rectal cancer, the sensitivity was 0.95, and the specificity was 0.88. The Hosmer-Lemeshow test results showed that the goodness of fit of the model was ideal ( P=0.823) . Conclusions:Age, maximum tumor diameter, differentiation degree, variance, skewness, and the 1 st percentile are independent factors in predicting tumor invasion depth in patients with early rectal cancer. The predictive model constructed based on these factors can effectively predict the risk of submucosal cancer in patients with early rectal cancer.

Objective To explore the feasibility,effectiveness,and safety of balloon catheter-assisted total hepatic vascular exclusion.Methods We designed and manufactured an endovascular catheter with three lumens and double balloons,which can be inserted into the retrahepatic inferior vena cava through the femoral vein.The superior and inferior vena cava of the liver can be blocked by filling balloon,and the total hepatic vascular exclusion was achieved by combining with pringle method.In animal experiments,total hepatic vascular exclusion was performed by balloon catheter-assist method(experimental group)or traditional methods(control group),and the complete time was compared between the two groups.Blood flow blocking effect was observed by angiography and incision of retrahepatic inferior vena cava under direct vision.The complications were recorded.Results Total hepatic vascular exclusion was successfully completed in both groups.The completion time in the experimental group was significantly shorter than that in the control group([12.5±1.2]min vs.[35.8±4.9]min,P<0.05).CT angiography,DSA,and direct vision of blood vessels all confirmed the effectiveness of balloon catheter-assisted hepatic blood flow exclusion.No catheter displacement,balloon rupture,or air embolism occurred.Conclusion The balloon catheter-assisted hepatic total vascular exclusion is simpler and more feasible than traditional method.

Acral melanoma(AM)is the most common histologic subtype of melanoma in dark-skinned patients and is associated with a worse prognosis and a high mortality rate,largely due to the inconspicuous nature of early-stage lesions,which can lead to late diagnosis.Because of the overlapping clinical and histopathological features of AM with other forms of cutaneous melanomas,early detection of AM requires a multidisciplinary approach that integrates various diagnostic modalities,including clinical examination,dermoscopy,histopathology,molecular testing,radiological imaging,and blood tests.While surgery is the preferred method of treatment for AM,other therapeutic options may be employed based on the stage and underlying etiology of the disease.Immune checkpoint inhibitors,molecular targeted therapy,radiotherapy,chemotherapy,and oncolytic virotherapy represent promising advanced treatment options for AM.In this review,we provide an overview of the latest advancements in diagnostic and therapeutic methods for AM,highlighting the importance of early detection and the prompt,individualized management of this challenging disease.

Objective:To investigate the status of cognition and clinical management of prolonged mechanical ventilation(PMV) among medical staffs in pediatric intensive care unit(PICU) in China, and in order to improve the awareness of PICU medical staffs on PMV and standardize the management of PMV.Methods:The cross-sectional study was conducted with doctors and nurses in PICUs of the collaborative group as the survey objects from July 12 to September 12, 2020.The questionnaire was issued, collected and checked by the Children′s Hospital of Fudan University.Results:(1) PMV related settings: Nine out of eleven hospitals had established PMV multidisciplinary teams, respiratory techniques such as diaphragm ultrasound and airway peak flow monitoring could be respectively executed in 72.7% and 36.4% of PICU.Pulmonary rehabilitation techniques such as airway clearance techniques, induced spirometer exercise, external diaphragm pacemaker stimulation, transfer bed exercise, balloon blowing, hyperbaric oxygen therapy could be respectively executed in 100.0%, 9.1%, 9.1%, 9.1%, 27.3% and 27.3% of PICU, respectively.(2) The cognitive status quo of children′s PMV: The most medical staffs agreed with the view that PMV referred to the children′s continuous mechanical ventilation for more than two weeks.Sixty percent of medical staffs believed that children with PMV had basic central nervous system diseases, and 62.7% of medical staffs believed that the most common causes of difficulty in PMV weaning was abnormal brain function.(3) The cognitive status quo of the children′s PMV management in PICU: Respondents believed that the most commonly used mechanical ventilation mode was synchronized intermittent mandatory ventilation+ pressure support ventilation in children′s PMV during stable disease.Ninety-two percent of medical staffs performed the spontaneous breathing test when weaning.And 58.7% of the respondents agreed to perform tracheotomy for the children during 3 to 4 weeks of mechanical ventilation.More than half of medical staffs would execute diaphragm function assessment, bedside rehabilitation training, nutritional assessment, analgesia and sedation assessment for children with PMV.(4) The cognitive status quo of the children′s PMV management of transition from hospital to family: 54.5% of PICU provided family care training to the family members before the children were discharged from the hospital.One center established the PMV specialized outpatient clinic.45.5% of PICU would follow up these discharged children one month later.Conclusion:At present, PICU medical staffs have different awareness of children′s PMV related problems in China.And children′s PMV lacks a systematic plan regarding diagnosis, treatment and management.

Effective methods for visualizing neurovascular morphology are essential for understanding the normal spinal cord and the morphological alterations associated with diseases. However, ideal techniques for simultaneously imaging neurovascular structure in a broad region of a specimen are still lacking. In this study, we combined Golgi staining with angiography and synchrotron radiation micro-computed tomography (SRμCT) to visualize the 3D neurovascular network in the mouse spinal cord. Using our method, the 3D neurons, nerve fibers, and vasculature in a broad region could be visualized in the same image at cellular resolution without destructive sectioning. Besides, we found that the 3D morphology of neurons, nerve fiber tracts, and vasculature visualized by SRμCT were highly consistent with that visualized using the histological method. Moreover, the 3D neurovascular structure could be quantitatively evaluated by the combined methodology. The method shown here will be useful in fundamental neuroscience studies.

Effective methods for visualizing neurovascular morphology are essential for understanding the normal spinal cord and the morphological alterations associated with diseases. However, ideal techniques for simultaneously imaging neurovascular structure in a broad region of a specimen are still lacking. In this study, we combined Golgi staining with angiography and synchrotron radiation micro-computed tomography (SRμCT) to visualize the 3D neurovascular network in the mouse spinal cord. Using our method, the 3D neurons, nerve fibers, and vasculature in a broad region could be visualized in the same image at cellular resolution without destructive sectioning. Besides, we found that the 3D morphology of neurons, nerve fiber tracts, and vasculature visualized by SRμCT were highly consistent with that visualized using the histological method. Moreover, the 3D neurovascular structure could be quantitatively evaluated by the combined methodology. The method shown here will be useful in fundamental neuroscience studies.
Animals ; Imaging, Three-Dimensional ; Mice ; Neural Networks, Computer ; Spinal Cord/diagnostic imaging* ; Synchrotrons ; X-Ray Microtomography

Objective:To explore the risk factors for mortality in pediatric acute respiratory distress syndrome (PARDS) requiring extracorporeal membrane oxygenation (ECMO) support.Methods:Clinical data of 109 patients with severe PARDS supported by ECMO, who were hospitalized in 6 ECMO centers in China from September 2012 to February 2020, were retrospectively analyzed. They were divided into survival group and death group according to the prognosis. Chi-square test and rank sum test were used to compare the variables between the two groups, including the demographic data, laboratory examination results, clinical data before and after ECMO, and other supportive treatment. Univariate and multivariate Logistic regression models were used to analyze the prognostic risk factors.Results:In these 109 cases, 54 died and 55 survived. Compared with the survival group, the death group had higher incidences of acute kidney injury (AKI) (48.1% (26/54) vs. 21.8% (12/55) , χ2=8.318, P=0.004) and coagulation dysfunction (22.2% (12/54) vs. 7.3% (4/55) , χ2=4.862, P=0.027), and higher rate of renal replacement therapy (48.1% (26/54) vs. 21.8% (12/55) , χ2=9.694, P=0.008) during ECMO support. Logistic regression analysis showed that continuous renal replacement therapy (CRRT) and AKI were independent risk factors for death in patients with severe PARDS requiring ECMO support ( HR=3.88,95% CI 1.04-14.52, HR=4.84,95% CI 1.21-19.46, both P<0.05). Conclusion:AKI and CRRT are independent risk factors for predicting mortality in patients with severe PARDS requiring ECMO support.

Objective:To assess antimicrobial activity of Fe 3O 4 nanozymes against Candida albicans. Methods:Fe 3O 4 nanozymes were prepared by using a modified hydrothermal synthesis method. Candida albicans suspensions were divided into 4 groups: nanozyme group treated with 0.5 g/L Fe 3O 4 nanozymes, H 2O 2 group treated with 0.1% H 2O 2, combination group treated with 0.5 g/L Fe 3O 4 nanozymes and 0.1% H 2O 2, and control group receiving no treatment. Candida albicans in the above 4 groups was all cultured with Sabouraud liquid medium, the absorbance value at 600 nm was detected every 2 hours, and the growth of Candida albicans was observed. After 2-hour treatment, the morphology of Candida albicans in the 4 groups was observed by scanning electron microscopy; after plate coating, Candida albicans was cultured at 36 ℃ for 48 hours, colonies were observed and counted, and the inhibition rate of colony formation was calculated. One-way analysis of variance was used for comparing means among several groups, and least significant difference (LSD) - t test for multiple comparisons. Results:A relatively stable survival curve of Candida albicans was observed in the control group, while the growth of Candida albicans was inhibited in the nanozyme group, H 2O 2 group and combination group. The colony count significantly differed among the control group, H 2O 2 group, nanozyme group and combination group (124 830 ± 45 170, 86 330 ± 13 960, 91 670 ± 31 370 and 30 330 ± 3010 respectively; F = 9.41, P < 0.05) , and was significantly lower in the combination group than in the control group ( t = 4.63, P < 0.05) . There was a significant difference in the colony-formation inhibition rate among the H 2O 2 group, nanozyme group and combination group (30.84% ± 5.00%, 26.57% ± 11.24%, 75.70% ± 2.42% respectively; F = 9.413, P < 0.01) , and the combination group showed a significantly higher inhibition rate compared with the H 2O 2 group and nanozyme group ( t = 8.08, 4.27 respectively, both P < 0.01) . Scanning electron microscopy showed changes in the morphology of Candida albicans treated with H 2O 2 and nanozymes alone or in combination, including shrinkage, rupture and even collapse. Conclusion:Fe 3O 4 nanozymes combined with H 2O 2 have obvious antimicrobial effect against Candida albicans.

Objective To investigate the effect of hyperoside on proliferation and killing activity of NK cells against pancreatic cancer PANC1 cells in vitro,and explore its potential mechanism.Methods Peripheral blood mononuclear cells of healthy donors were isolated,NK cells were induced with medium contained with IL-2 and different concentrations of hyperoside (0.3,1.6,8,40 and 200 μg/ml) for 12 days.Cell viability was observed by trypan blue staining.Phenotype and perforin,granzyme B expression of NK cells were detected by flow cytometry.Killing activity of NK cells against PANC1 cells were analyzed with lactate dehydrogenase (LDH) releasing method.Results The proportion of NK cells in control group and experimental group treated with different concentration of hyperoside both reached about 80％,respectively.The proliferation of CDs-CD56 + NK cells treated by hyperoside at 0.3,1.6 and 8 μg/ml was (93.76 ±8.77),(106.67 ± 12.35) and (118.50 ± 11.51) times,respectively,which were significantly higher than (73.70 ± 9.43) times of the control group.The expressions of perforin in NK cells treated with hyperoside at 1.6,8 and 40 μg/ml were significantly higher than those of the control group [(82.34 ± 2.90) ％,(89.15 ±3.54) ％,(81.78 ± 2.81)％ vs (72.93 ± 2.06)％].The expressions of granzyme B in NK cells treated with hyperoside at 1.6 and 8 μg/ml were significantly higher than those of the control group [(87.30 ± 1.70) ％,(92.16 ±3.05)％ vs (82.35 ±2.73)％].The killing activity of NK cells against PANC1 cells treated by hyperoside at 1.6 and 8 μg/ml was significantly higher than those of the control group [(63.18 ± 3.77)％,(65.34 ± 4.97) ％ vs (52.16 ± 5.48) ％].The differences were statistically significant (all P ＜ 0.05).Conclusions Hyperoside could promote the proliferation of NK cells at certain concentrations and maybe enhance the killing effect against pancreatic cancer PANC1 cells through up-regulating the expression of perforin and granzyme B in NK cells.