BACKGROUND:Inflammation,oxidative stress and bacterial infection are the main causes of delayed wound healing in diabetes.In recent years,various inorganic nanomaterials have been widely used in the treatment of skin wound healing due to their antibacterial activities,but their effects on anti-oxidation and anti-inflammation are limited. OBJECTIVE:To investigate the effect of Prussian blue nanoparticles on the wound repair of diabetes in terms of antioxidant,anti-inflammatory and photothermal antibacterial activities. METHODS:Prussian blue nanoparticles were prepared and characterized.(1)In vitro:The biocompatibility of Prussian blue nanoparticles with different concentrations was detected by MTT assay.The cytoprotective effect of Prussian blue nanoparticles and the intracellular reactive oxidative species level were examined under the condition of hydrogen peroxide.The ability of Prussian blue nanoparticles to decompose hydrogen peroxide and superoxide anion radicals was tested;the effect of Prussian blue nanoparticles on lipopolysaccharide-induced macrophage inflammation was investigated.The photothermal antibacterial activity of Prussian blue nanoparticles was detected by the plate colony counting method.(2)In vivo:ICR mice were intraperitoneally injected with streptozotocin to establish a diabetes mouse model.After the model was successfully established,a 6 mm wound was created on the back with a hole punch.There were the control group(no treatment),the Prussian blue group and the Prussian blue with light group.The wound healing and histomorphological changes were observed. RESULTS AND CONCLUSION:(1)In vitro:Prussian blue nanoparticles in 25-200 μg/mL were non-toxic to cells.Prussian blue nanoparticles had the extremely strong antioxidant capacity and mitigated the intracellular reactive oxidative species at a high oxidative stress environment,resulting in a pronounced cytoprotective effect.The Prussian blue nanoparticles not only exhibited hydrogen peroxide degradation activity but also showed strong superoxide scavenging ability.Prussian blue nanoparticles also displayed significant anti-inflammatory activity and extremely strong antibacterial ability after light irradiation.(2)In vivo:After 14 days,the wound sizes of the Prussian blue group and Prussian blue with light group were significantly reduced,and the healing speed of Prussian blue with light group was the fastest.Hematoxylin-eosin and Masson staining showed a lot of granulation tissue formation and collagen deposition in the Prussian blue group and the Prussian blue with light group,of which the Prussian blue with light group was the most.Immunofluorescence staining displayed that,compared with the control group,the expressions of α-SMA and CD31 were increased significantly in Prussian blue group and Prussian blue with light group(P<0.05),but F4/80 expression was decreased significantly in Prussian blue group and Prussian blue with light group(P<0.05),indicating more obvious improvement in the Prussian blue with light group.(3)These results showed that Prussian blue nanoparticles could promote the skin wound healing of the diabetes mouse model by exerting anti-inflammatory,antioxidant and antibacterial effects.

Objective To explore the pharmacokinetics/pharmacodynamics(PK/PD)parameters and influencing factors in patients with augmented renal clearance(ARC)to provide the basis for the rational use of meropenem.Methods Using the method of retrospective study,the patients with increased renal clearance who used meropenem monitored the concentration from January 2018 to December 2021.The PK/PD parameters of meropenem were analyzed,and multiple linear retrospective analyses discussed the influencing factors of meropenem valley concentration.Results A total of 58 patients were included in the study,and the trough concentration was 1.35[0.23,1.86]μg·mL-1,taking 100%fT＞MIC as PK/PD target value,the compliance rate was 20.69%.The compliance rate of daily dose＜3 g·d-1 was 8.70%,and≥3 g·d-1 was 31.43%,the difference was statistically significant.With MIC of 0.5,1,2,4,and 8 μg·mL-1,PK/PD compliance rates were 62.07%,48.28%,20.69%,8.62%and 0.Respectively.Multiple linear retrospective analyses showed that dose was an independent factor affecting meropenem valley concentration.Conclusion The PK/PD compliance rate of meropenem in patients with augmented renal clearance is low,even if MIC≤0.5 μg·mL-1,the routine dose is difficult to achieve the ideal PK/PD,so the clinical should recognize ARC and perform TDM as soon as possible,and use TDM to guide the medication regimen of meropenem for ARC patients.

Objective To study the effect of curcumin on wound healing in diabetic mice.Methods The effect of curcumin on fibroblast activity was examined by the MTT assay,and the ROS detection kit was used to detect the effect of curcumin on the hydrogen peroxide-induced scavenging effect of reactive oxygen species(ROS)in fibroblasts.Q-PCR was used to detect the effects of curcumin on the mRNA expression of inflammatory factors CD86,CD206,IL-6 and ARG1 in lipopolysaccharide-induced RAW 264.7macrophage.The wound model of diabetes was established by intraperitoneal injection of streptozotocin.Hematoxylin-eosin(HE)and Masson staining were used to evaluate wound healing and histomorphological changes,and immunofluorescence staining was used to determine skin tissue α-smooth muscle actin,CD86 and CD206 expression.Results Curcumin had no significant effect on fibroblast activity at concentrations less than 20 mol·L-1;curcumin scavenged hydrogen peroxide-induced intracellular ROS in fibroblasts;curcumin decreased the mRNA expression of CD86 and IL-6 while increasing CD206 and ARG1 in lipopolysaccharide-induced RAW 264.7 macrophages.After in vivo administration,compared with the control group,wound healing was significantly faster in the curcumin(15,30 mg·mL-1)group after 7 d and 14 d of wound perforation(P＜0.01).Hematoxylin-eosin(HE)and Masson staining results confirmed a significant increase in granulation tissue and a significant increase in collagen deposition in the curcumin(15,30 mg·mL-1)group.Immunofluorescence assay showed significantly higher expression of CD206(P＜0.01)and significantly reduced expression of CD86(P＜0.01)in the skin wounds of curcumin(15,30 mg·mL-1)for 14 d.In addition,the expression of α-SMA in the wound of the high-dose curcumin(30 mg·mL-1)group was significantly higher than that of the low-dose curcumin group(P＜0.01).Conclusion Curcumin accelerates diabetic wound healing by promoting granulation tissue proliferation and collagen deposition in refractory diabetic wounds in mice through its anti-inflammatory and antioxidant effects.

Objective: To investigate the prognostic utility of radiomics features extracted from 18 F-fluorodeoxyglucose (FDG) PET/CT combined with clinical factors and metabolic parameters in predicting progression-free survival (PFS) and overall survival (OS) in individuals diagnosed with extranodal nasal-type NK/T cell lymphoma (ENKTCL). Materials and Methods: A total of 126 adults with ENKTCL who underwent 18 F-FDG PET/CT examination before treatment were retrospectively included and randomly divided into training (n = 88) and validation cohorts (n = 38) at a ratio of 7:3.Least absolute shrinkage and selection operation Cox regression analysis was used to select the best radiomics features and calculate each patient’s radiomics scores (RadPFS and RadOS). Kaplan–Meier curve and Log-rank test were used to compare survival between patient groups risk-stratified by the radiomics scores. Various models to predict PFS and OS were constructed, including clinical, metabolic, clinical + metabolic, and clinical + metabolic + radiomics models. The discriminative ability of each model was evaluated using Harrell’s C index. The performance of each model in predicting PFS and OS for 1-, 3-, and 5-years was evaluated using the time-dependent receiver operating characteristic (ROC) curve. Results: Kaplan–Meier curve analysis demonstrated that the radiomics scores effectively identified high- and low-risk patients (all P < 0.05). Multivariable Cox analysis showed that the Ann Arbor stage, maximum standardized uptake value (SUVmax), and RadPFS were independent risk factors associated with PFS. Further, β2-microglobulin, Eastern Cooperative Oncology Group performance status score, SUVmax, and RadOS were independent risk factors for OS. The clinical + metabolic + radiomics model exhibited the greatest discriminative ability for both PFS (Harrell’s C-index: 0.805 in the validation cohort) and OS (Harrell’s C-index: 0.833 in the validation cohort). The time-dependent ROC analysis indicated that the clinical + metabolic + radiomics model had the best predictive performance. Conclusion The PET/CT-based clinical + metabolic + radiomics model can enhance prognostication among patients with ENKTCL and may be a non-invasive and efficient risk stratification tool for clinical practice.

Objective:To investigate the value of intratumoral and peritumoral radiomics features of multi-parameter MRI in evaluation of the status of human epithelial growth factor receptor 2 in breast cancer.Methods:The clinical, pathological and imaging data of 340 patients with pathologically confirmed breast cancer in Henan Provincial People′s Hospital from September 2019 to December 2020 were retrospectively collected. All patients were female, 48 (42, 55) years old. All patients underwent multi-parameter breast MRI before surgery, including dynamic contrast-enhanced T 1WI (DCE-T 1WI), fat-suppressed T 2WI (T 2WI) and diffusion-weighted imaging (DWI). The region of interest (ROI) for lesions were manually delineated and the segmented ROIs were zoomed in ring shape by 4 mm to acquire ROI intra and ROI prei, respectively. Then six sets of radiomics features were extracted from ROI intra and ROI prei of DCE-T 1WI, T 2WI and DWI. The cases were divided into a training set (272 cases) and a test set (68 cases) by stratified sampling at a ratio of 4∶1. The Mann-Whitney U test, Select K Best and minimum absolute contraction and selection operator were used for feature selection of the 6 sets of radiomics features. The feature subsets after reduction were used to construct independent and combined radiomics signatures with support vector machine algorithm to predict the HER2 status of breast cancer. Receiver operating characteristic curve was generated and area under curve (AUC) was calculated to compare the prediction performance of different models. Results:Of the 340 patients, 80 were HER2-positive and 260 were HER2-negative. Among the radiomics signatures based on single sequence, the DWI peri showed the best performance in predicting HER2 status of breast cancer, with an AUC of 0.678 for the test set. Among the combination of intratumoral and peritumoral radiomics signatures based on same sequence, the DWI intra+DWI peri had the highest prediction value, achieving an AUC of 0.774 for the testing set. Among the intratumoral or peritumoral radiomics signatures derived from two different sequences, the DCE-T 1WI intra+DWI intra and T 2WI peri+DWI peri showed the best predictive performance, yielding AUC of 0.766 and 0.769 in the testing set, respectively. Among the combination of intratumoral or peritumoral radiomics signatures derived from all 3 sequences or combinations of all features, the DCE-T 1WI intra+T 2WI intra+DWI intra+DCE-T 1WI peri+T 2WI peri+DWI peri obtained the highest prediction efficiency, with an AUC of 0.913 for the testing set. Conclusion:The radiomics features of intratumoral and peritumoral regions based on multi-parameter MRI have a certain value in non-invasive evaluation of HER2 status of breast cancer, which can help clinicians to provide scientific basis for decision-making of targeted therapy in patients with breast cancer.

Objective:To investigate the MRI and pathological features of intramuscular fibro-adipose vascular anomaly (FAVA).Methods:The clinical and imaging data of 44 patients with intramuscular FAVA confirmed by pathology from December 2012 to March 2021 in Henan Province People′s Hospital were retrospectively analyzed. Twenty-five females and 19 males were included, with the age of (15±6), from 5 to 29 years old. The clinical and MRI features including the type, location, boundary, signal intensity, enhancement mode and degree, and the vascular flow voids in the lesion were summarized and compared with pathological results.Results:The thigh and calf muscles were involved in 1 patient simultaneously, and 1 site was involved in 43 patients, including 20 calf muscles, 15 thigh muscles, 5 forearm muscles, 1 upper arm muscle, 1 gluteal muscle, and 1 shoulder muscle. The gastrocnemius muscle of lower leg was most commonly involved (13/44), followed by soleus muscle (10/44) and quadriceps femoris muscle (9/44). All the lesions were solid on MRI, including 24 cases of focal mass type, 15 cases of diffuse infiltration type and 5 cases of local infiltration type. The long axis of all the lesions were consistent with the long axis of the muscles. All lesions showed inhomogeneously moderate hyperintensity on T 1WI and T 2WI, and significantly hyperintensity on fat suppression T 2WI. All lesions showed tortuous and dilated abnormal vessels, of which 18 cases showed vascular flow voids. Thrombosis was found in 10 cases. On contrast-enhanced imaging, the lesions showed moderate to obvious inhomogeneous enhancement. Pathologically, the diseased skeletal muscle was infiltrated by fibrous tissue, fat components, irregular abnormal veins and vessels, which led to inhomogeneous MRI signals. Among the 7 patients who underwent human PIK3CA gene mutation detection, and 6 were mutant. Conclusions:Intramuscular FAVA has certain characteristics in clinic, MRI imaging and histopathology, and its MRI signal characteristics can reflect its complex pathological components.

Objective:To explore the detection and segmentation of ischemic core infarct volume of the acute stroke in diffusion weighted imaging (DWI) images using cascaded VB-Net.Methods:MRI data of 1 500 patients (2 456 lesions) with acute ischemic stroke in Henan Provincial People′s Hospital from December 2016 to December 2018 were retrospectively analyzed. Firstly, manual segmentation of ischemic core was performed on DWI images (b=1 000 s/mm 2), and then all data were divided into training set, validation set and independent test set by 8∶1∶1. Then, the cascaded VB-Net was constructed, and the core infarct was automatically detected and segmented in the test set. Interclass correlation coefficient (ICC) was used to evaluate the consistency of volume size measured by manual segmentation and cascaded VB-Net. The patients were divided into large ischemic core lesion group (ischemic core volume ≥10 ml) and small ischemic core lesion group (ischemic core volume<10 ml), and the Dice coefficient difference between the two groups was compared using Mann-Whitney U test. Results:In independent test set, cascaded model had the detection rate of 94.6% (243/257) with Dice coefficient of 0.76 (0.68, 0.84). The agreement of cacade VB-Net segmented [4.19(1.21,14.13)ml] and manual segmented ischemic core infarct volume [4.08(1.19,17.92)ml] was high (ICC=0.97, P<0.001). There was no significant difference in Dice coefficient between large and small lesion groups [0.76 (0.69, 0.85), 0.76 (0.67, 0.84), Z=-0.44, P=0.657]. Conclusions:The cascaded VB-Net model provided a tool to realize automatic detection, segmentation, and calculation of ischemic core infarct volume. It has good segmentation accuracy and high consistency with manual segmentation, which can provide an auxiliary decision-making tool for the selection of treatment plans.

Objective:To assess the role of arterial spin labeling (ASL) in detecting the blood-brain barrier (BBB) permeability of cerebral infarction lesions in patients with anterior circulation subacute ischemic stroke (SIS), and to evaluate the value of ASL in predicting hemorrhagic transformation (HT) of SIS patients after endovascular recanalization.Methods:A prospective analysis was performed. Patients with anterior circulation SIS who received endovascular treatment (EVT) in our hospital from January 2021 to September 2021 were enrolled. At 24 h before EVT and immediately after EVT, MRI scans of ASL sequences and dynamic contrast-enhanced magnetic resonance (DCE) sequence were completed, and Xper CT was performed; accordingly, imaging typing was performed. Head CT scan was performed 24-48 h after EVT to observe HT; according to the presence or absence of HT, these patients were divided into HT group and non-HT group; the relative cerebral blood flow (rCBF) values of ASL sequence parameters, volume transfer constant (K trans) of DCE sequence parameters and the differences of ASL, DCE and Xper CT imaging types between the two groups were compared. The weighted Kappa coefficient was used to test the consistency among ASL, DCE and Xper CT imaging types. Results:Among 22 eligible patients, 5 patients occurred HT (5/22, 22.72%). As compared with those in the non-HT group (1.14±0.04; 0.032[0.024, 0.039]/min), patients in the HT group had significantly higher rCBF value (1.57±0.18) and K trans (0.072[0.0455, 0.117]/min, P<0.05). There were significant differences in the distribution of ASL, DCE and Xper CT imaging types between the two groups ( P<0.05); among them, 4 out of 6 patients with ASL imaging type III, 4 out of 6 patients with DCE imaging type III, and 4 out of 5 patients with Xper CT imaging type III had HT. ASL sequence and DCE sequence had a high consistency in the imaging types (Kappa coefficient=0.941, 95%CI: 0.862-1.020, P<0.001). Conclusion:ASL can effectively evaluate the BBB permeability of cerebral infarction lesions in patients with anterior circulation SIS; patients with ASL imaging type III have a relatively high risk of HT.

Objective:To assess the role of arterial spin labeling (ASL) in detecting the blood-brain barrier (BBB) permeability of cerebral infarction lesions in patients with anterior circulation subacute ischemic stroke (SIS), and to evaluate the value of ASL in predicting hemorrhagic transformation (HT) of SIS patients after endovascular recanalization.Methods:A prospective analysis was performed. Patients with anterior circulation SIS who received endovascular treatment (EVT) in our hospital from January 2021 to September 2021 were enrolled. At 24 h before EVT and immediately after EVT, MRI scans of ASL sequences and dynamic contrast-enhanced magnetic resonance (DCE) sequence were completed, and Xper CT was performed; accordingly, imaging typing was performed. Head CT scan was performed 24-48 h after EVT to observe HT; according to the presence or absence of HT, these patients were divided into HT group and non-HT group; the relative cerebral blood flow (rCBF) values of ASL sequence parameters, volume transfer constant (K trans) of DCE sequence parameters and the differences of ASL, DCE and Xper CT imaging types between the two groups were compared. The weighted Kappa coefficient was used to test the consistency among ASL, DCE and Xper CT imaging types. Results:Among 22 eligible patients, 5 patients occurred HT (5/22, 22.72%). As compared with those in the non-HT group (1.14±0.04; 0.032[0.024, 0.039]/min), patients in the HT group had significantly higher rCBF value (1.57±0.18) and K trans (0.072[0.0455, 0.117]/min, P<0.05). There were significant differences in the distribution of ASL, DCE and Xper CT imaging types between the two groups ( P<0.05); among them, 4 out of 6 patients with ASL imaging type III, 4 out of 6 patients with DCE imaging type III, and 4 out of 5 patients with Xper CT imaging type III had HT. ASL sequence and DCE sequence had a high consistency in the imaging types (Kappa coefficient=0.941, 95%CI: 0.862-1.020, P<0.001). Conclusion:ASL can effectively evaluate the BBB permeability of cerebral infarction lesions in patients with anterior circulation SIS; patients with ASL imaging type III have a relatively high risk of HT.

We here report the diagnosis and treatment of tricho-hepato-enteric syndrome in a female neonate. The 11-day-old patient, born at a gestational age of 38 weeks and with a birth weight of 1 700 g, was admitted to the Affiliated Hospital of Jining Medical University in January 2019 due to "skin stained yellow for 6 d". She presented with yellow, thin, and sparse hair that was easy to fall off, intractable diarrhea, repeated fever, and slow weight gain, further complicated by congenital heart disease. After 25-days of treatment, the child's infection was under control, but still had diarrhea. The baby girl was discharge later on request of her parents, but readmitted at the age of 3 months due to pulmonary infection. Delayed development, malnutrition, prominent forehead, wide eye distance, low nasal bridge, hepatomegaly, and intractable diarrhea were also observed. Whole exome sequencing identified a homozygous mutation of c.2344delC(p.His782fs) in SKIV2L gene in the baby, and both her parents were heterozygous carriers of the mutation at this site. She was diagnosed with SKIV2L gene mutation-induced tricho-hepato-enteric syndrome. The patient suffered from sustained diarrhea and recurrent infection and died of infection at 4 months of age after her parents' decision to withdraw treatment.