Two novel diketopiperazines (1 and 5), along with ten known compounds (2-4, 6-12) demonstrating significant skin inflammation inhibition, were isolated from a marine-derived fungus identified as Aspergillus sp. FAZW0001. The structural elucidation and configurational reassessments of compounds 1-5 were established through comprehensive spectral analyses, with their absolute configurations determined via single crystal X-ray diffraction using Cu Kα radiation, Marfey's method, and comparison between experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1, 2, and 8 exhibited significant anti-inflammatory activities in Propionibacterium acnes (P. acnes)-induced human monocyte cell lines. Compound 8 demonstrated the ability to down-regulate interleukin-1β (IL-1β) expression by inhibiting Toll-like receptor 2 (TLR2) expression and modulating the activation of myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB) signaling pathways, thus reducing the cellular inflammatory response induced by P. acnes. Additionally, compound 8 showed the capacity to suppress mitochondrial reactive oxygen species (ROS) production and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing IL-1β maturation and secretion. A three-dimensional quantitative structure-activity relationships (3D-QSAR) model was applied to compounds 5-12 to analyze their anti-inflammatory structure-activity relationships.
Humans ; Aspergillus/chemistry* ; Diketopiperazines/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Interleukin-1beta/genetics* ; Toll-Like Receptor 2/immunology* ; Propionibacterium acnes/drug effects* ; NF-kappa B/genetics* ; Molecular Structure ; Myeloid Differentiation Factor 88/immunology* ; Monocytes/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Cell Line

Objective To summarize the clinical experience of the treatment for complex aortic coarctation with extra anatomic bypass and anatomic correction techniques. Methods The clinical data of patients with complex aortic coarctation treated in the First Affiliated Hospital of Nanjing Medical University and Friendship Hospital of Ili Kazakh Autonomous Prefecture between April 2012 and November 2020 were retrospectively reviewed. Results A total of 12 patients were enrolled, including 5 males and 7 females aged 11-54 (34.3±16.2) years. Extra anatomic bypass grafting was performed in 8 patients and anatomic correction was performed in 4 patients. The operations were successful in all patients. There was no perioperative death. The average cardiopulmonary bypass time was 203.0±46.0 min (7 median incision patients), and the average intraoperative blood loss was 665.0±102.0 mL. The average postoperative ventilator support time was 32.3±7.5 h, and the average postoperative hospital stay time was 10.2±4.3 d. The mean drainage volume of median incision was 1 580.0±360.0 mL, and the mean drainage time was 9.3±2.7 d. The mean drainage volume of left thoracotomy was 890.0±235.0 mL, and the mean drainage time was 4.8±2.5 d. One patient had a transient hoarse after operation and recovered 6 months later. The follow-up period ranged from 2 to 10 years with an average time of 81.0±27.0 months. All patients had a recovery of hypertension, cardiac afterload after 2 years postoperatively. One patient who received an artificial blood vessel replacement in situ was examined stenosis recurrence at the third year after discharge. Others were asymptomatic during the follow-up period. There were no death or other complications. Conclusion The treatment strategy for complex aortic coarctation should be individualized according to the anatomical features and concomitant heart diseases. Extra anatomic bypass technique is a safe and feasible choice.

Objective:To investigate the effects of over-expression of E2F transcription factor 1 (E2F1) on proliferation, invasion, apoptosis and radiosensitivity of glioma cell U251.Methods:Real-time quantitative PCR (qRT-PCR) were used to detect the differential expression of E2F1 mRNA in glioma cells LN18, SW1088, U251 and normal brain glial cells. The stable over-expression of E2F1 plasmid was constructed and transfected into U251 cells. qRT-PCR and Western blot test were used to detect the expression of E2F1, pituitary tumor transforming gene 1(PTTG1), C-Myc, B-cell lymphoma-2 (Bcl-2), Bcl2-associated X (Bax) mRNA and protein expression in the control group and E2F1 over-expression group.U251 cells were divided into control group(no X-ray irradiation), irradiation group(6 Gy dose of X-ray), and irradiation + E2F1 over-expression group(transfected with E2F1 first, then irradiated by 6 Gy of X-ray). Cell proliferation ability was detected by cell counting Kit-8(CCK-8) cell viability detection reagent, and cell invasion and migration ability were detected by Transwell chamber. Apoptosis and cell cycle were detected by flow cytometry.GraphPad Prism 8.0 was used for data analysis.The statistical methods were one-way ANOVA and independent sample t-test. Results:qRT-PCR showed that there was statistical difference in the mRNA levels of E2F1( F=201.92, P<0.05) in different cell lines.The expression levels of E2F1 mRNA in LN18(4.04±0.29), SW1088(3.19±0.16)and U251(4.66±0.20) cells were higher than those in HEB(1.02±0.07)cells ( q=27.00, 19.40, 32.52, all P<0.05). After successfully constructing U251 cells with stable over-expression of E2F1 plasmid, qRT-PCR and Western blot detection results showed that: the mRNA and protein levels of E2F1, PTTG1, C-Myc and Bcl-2 in E2F1 over-expression group were higher than those in control group ( t=77.16, 57.88, 4.63, 51.13, 7.50, 70.85, 8.38, 48.81, all P<0.05). Bax mRNA(0.20±0.01) and protein(0.66±0.01) levels were lower than those in control group((1.00±0.02), (0.94±0.01)), and the differences were statistically significant ( t=1.74, 54.65, both P<0.05). After X-ray irradiation (6 Gy), CCK8 detection results showed: the proliferation ability of the three groups at 24, 48, 72 and 96 h were significantly different ( F=95.41, 187.53, 1 158.49, 7 883.78, all P<0.05). The proliferation capacity of the irradiation group were lower than those of the control group at 24, 48, 72 and 96 h ( q=19.51, 27.20, 66.60, 174.9, all P<0.05). The proliferation capacity of irradiation + E2F1 over-expression group at 24, 48, 72 and 96 h were higher than those of irradiation group ( q=10.63, 10.81, 21.11, 60.90, all P<0.05). Transwell assay results showed that there were significant differences in cell invasion and migration ability among the three groups ( F=315.38, 681.10, both P<0.05). The invasion and migration ability of cells in the irradiation group were lower than those in the control group ( q=35.09, 12.76, both P<0.05), and the invasion and migration ability of cells in the irradiation + E2F1 over-expression group were higher than those in the irradiation group ( q=52.06, 22.81, both P<0.05). Flow cytometry showed that there were significant differences in apoptosis rate and percentage of cells in each cycle among the three groups ( F=667.63, 3 213.30, 3 011.26, 861.98, all P<0.05). The percentage of the apoptosis rate, S phase and G2 phase cells in the irradiation group were higher than those in the control group ( q=51.10, 89.39, 51.82, all P<0.05), while the percentage of G1 phase cells in the irradiation group was lower than that in the control group ( q=141.2, P<0.05). The apoptosis rate and percentage of S phase and G2 phase cells in the irradiation + E2F1 over-expression group were lower than those in the irradiation group ( q=18.87, 41.42, 29.31, all P<0.05), while the number of G1 phase cells in the irradiation + E2F1 over-expression group was lower than that in the irradiation group ( q=70.73, P<0.05). Conclusion:Over-expression of E2F1 can reduce the radiosensitivity of glioma U251 cells by regulating the expression of mRNA and protein of genes related to cell cycle and apoptosis, and E2F1 may be involved in the radioresistance of glioma cells.

Objective:To analyze and summarize clinical and pathological characteristics of clear cell papulosis (CCP) .Methods:Clinical data were collected from 57 children with CCP, who were diagnosed in Department of Dermatology, Children′s Hospital of Chongqing Medical University from November 2014 to March 2022, and their clinical and pathological characteristics were analyzed.Results:Among the 57 patients, 30 were males and 27 were females; their age ranged from 6 months to 7 years and 10 months; the age at onset ranged from 1 to 74 months, and 39 (68.4%) experienced onset of disease in infancy; the course of disease ranged from 1 to 84 months. Skin lesions mainly manifested as millet- to soybean-sized roundish white macules or short bar-like white macules measuring 1 - 2 cm in length. Most patients (49 cases, 85.9%) had skin lesions less than 20 in number. The most common location of skin lesions was the lower abdomen (35 cases, 61.4%), followed in turn by chest or upper abdomen (34 cases, 59.6%), anterior axilla or armpit (17 cases, 29.8%), and vulva (11 cases, 19.3%). Short bar-like white macules predominated on the chest or upper abdomen (23/34, 65.7%) and anterior axilla or armpit (10/17), roundish white macules predominated on the lower abdomen (30/35, 85.7%), and the vulvar lesions all manifested as roundish white macules. Histopathological findings showed that slightly larger cells with abundant clear cytoplasm were scattered in or above the basal layer of the epidermis, and these cells were positive for cytokeratin 7, carcinoembryonic antigen, and periodic acid-Schiff staining.Conclusion:CCP mainly occurred in young children, roundish white macules predominated on the lower abdomen and vulva, and short bar-like white macules predominated on the chest or upper abdomen, as well as on the anterior axilla or armpit, indicating that CCP has strongly identifiable clinical features.

Objective:To evaluate the predictive value of the National Institutes of Health Stroke Scale(NIHSS)score and the Glasgow Coma Scale(GCS)score for bleeding in patients with acute cerebral infarction after thrombolytic therapy.Methods:A total of 281 patients with acute cerebral infarction were enrolled at Henan Provincial People's Hospital and were treated with urokinase or recombinant human tissue plasminogen activator(rt-PA)for thrombolysis.The patients were followed up for up to 1 month after thrombolysis.Data on age, sex, time to thrombolysis, smoking, systolic blood pressure, platelets, prothrombin time, international normalized ratio, and NIHSS and GCS scores were collected.Logistic regression analysis was used to identify related factors for bleeding after thrombolysis in acute cerebral infarction and the receiver-operating characteristic curve(ROC)was used to assess the predictive values of these factors through calculating the area under the curve(AUC).Results:Logistic regression analysis showed that time to thrombolysis, prothrombin time before thrombolysis, NIHSS score before thrombolysis, NIHSS score 24 h after thrombolysis, GCS score before thrombolysis, and GCS score 24 h after thrombolysis were independent factors for hemorrhage after thrombolytic therapy( OR=23.318, 0.238, 17.099, 4.561, 0.004, and 0.258, P=0.038, 0.021, 0.038, 0.027, 0.006, and 0.040, respectively).ROC curve analysis showed that NIHSS score before thrombolysis, NIHSS score 24 h after thrombolysis, and time to thrombolysis were important factors for predicting bleeding after thrombolysis(AUC=0.833, 0.795, and 0.714, respectively, all P=0.000). Conclusions:For patients with acute cerebral infarction, the risk of bleeding after thrombolysis is significantly increased if the NIHSS score is unfavorable before thrombolysis or 24 h after thrombolysis, or the duration of acute cerebral infarction is long.Attention to risk factors and early intervention are warranted.

Objective:To construct a serine protease inhibitor Kazal type-5 (Spink5) conditional knockout mouse model, and to identify its phenotype.Methods:B cell-specific Spink5 conditional knockout mice of genotype Mb1 cre/+Spink5 floxp/floxp were constructed by using clustered regularly interspaced short palindromic repeats (CRISPR) /CRISPR-associated protein 9 (Cas9) technology, and served as the knockout group. Mice of genotype Mb1 +/+Spink5 floxp/floxp served as the control group. The mice of genotype Mb1 cre/+Spink5 floxp/floxp or Mb1 +/+Spink5 floxp/floxp were sacrificed when they were 4 to 6 weeks old, splenic mononuclear cells were isolated, and B lymphocytes and non-B lymphocytes were sorted by flow cytometry and fluorescence-activated cell sorting. Genotype identification was performed by PCR, and protein expression of lymphoepithelial Kazal-type-related inhibitor (LEKTI) was determined by Western blot analysis. Skin tissues were resected from the mice, and subjected to hematoxylin-eosin staining for measuring the epidermal thickness. Immunofluorescence staining was performed to determine fluorescence intensity of LEKTI protein in the mouse skin tissues. Paired t test or two-independent-sample t test was used for comparisons between groups. Results:Genotype identification results demonstrated that the stable B lymphocyte-specific Spink5 conditional knockout mouse model was successfully constructed. Western blot analysis revealed that the relative protein expression of LEKTI in the B lymphocytes in the knockout group was 0.01 ± 0.02, which was significantly lower than that in the non-B lymphocytes in the knockout group (0.66 ± 0.11, t = 9.99, P < 0.001) , and that in the B lymphocytes in the control group (1.08 ± 0.13, t = 13.78, P < 0.001) . Among 39 mice in the knockout group, 4 presented with dry skin and scattered scaly hypertrophic maculopapules. The epidermal thickness of the lesional skin tissues in the knockout group was 90.42 ± 21.31 μm, significantly higher than that of the non-lesional skin tissues in the knockout group (29.71 ± 3.63 μm, t = 5.05, P = 0.002) and that of normal skin tissues in the control group (12.42 ± 2.21 μm, t = 6.74, P < 0.001) . Immunofluorescence staining showed no significant difference in the fluorescence intensity of LEKTI protein among the lesional skin tissues (46.21 ± 1.21) , non-lesional skin tissues (46.62 ± 2.13) in the knockout group and normal skin tissues in the control group (47.69 ± 1.71, P > 0.05) . Conclusion:The B lymphocyte-specific Spink5 conditional knockout mouse model was successfully constructed, which provides a basis for further exploring mechanisms underlying skin barrier defects and immune dysfunction in Netherton syndrome.

Objective:To investigate the clinicopathological features, treatment programs and prognosis of patients with primary diffuse large B-cell lymphoma (DLBCL) in cavernous sinus.Methods:The clinical data of a patient with primary DLBCL in cavernous sinus who were admitted to Wuhan No.1 Hospital in December 2020 were retrospectively analyzed, and the relevant literature was reviewed.Results:The patient was a 63-year-old female who underwent resection of the cavernous sinus lesion, and the pathological diagnosis was DLBCL. The patient received 6 courses of R-CHOP regimen chemotherapy, lumbar puncture + intrathecal injection of chemotherapy drugs, and twice additional rituximab immunochemotherapy, and no tumor cells were found in the results of liquid-based thin layer cytology for cerebrospinal fluid exfoliated cells; twice magnetic resonance imaging (MRI) re-examination after the operation showed no recurrence and adjacent metastasis of the tumor. The patient's symptoms were significantly improved without residual neurological sequelae.Conclusions:Primary DLBCL in cavernous sinus is rare in clinical practice, early diagnosis is crucial for the prognosis of patients, and different protein expression may indicate the prognosis. Biopsy, complete resection of the tumor under the premise of preserving important anatomical structures and functions, and standardized chemotherapy combined with intrathecal injection local chemotherapy can effectively prolong the survival time of patients and improve the quality of life.

Objective:To explorethe the clinical manifestations, treatment and prognosis of anastomotic pseudoaneurysm after renal transplantation caused by infection.Methods:Clinical data of 1 recipient with pseudoaneurysm after renal transplantation due to Pseudomonas aeruginosa infection were retrospectively analysed and combined with a literature review. Results:At Month 2 post-transplantation, the recipient developed right lower abdominal pain, and contrast-enhanced ultrasound examination showed a pseudoaneurysm at the artery anastomosis. Anti-infection and anti-rejection therapy had no obvious effect, and therefore next surgical exploration was performed. A size4.0 cm×3.5cm pseudoaneurysm was found intraoperatively at the graft renal artery anastomosis.After graft was evaluated as having no preservation value, the transplanted kidney and pseudoaneurysm were resected. Bacterial culture indicated Pseudomonas aeruginosa infection.The recipient recovered well and waited for next transplantation. Conclusions:Pseudoaneurysm of transplanted kidney is a very rare complication after renal transplantation, and caused by infection of Pseudomonas aeruginosa is more rarer, It has not been reported in mainland China.This type of recipient has the characteristics of high graft inactivation rate and high mortality rate. Timely surgical resection can effectively prevent the deterioration of disease.

Objective:This study aimed to investigate the changes of ventricular repolarization index on ECG and its relationship between prognosis in patients with acute cerebral trauma.Methods:From January 2014 to January 2018, data of 289 consecutive patients with emergency traumatic brain injuries were prospectively collected and ultimately 219 cases were selected into the study group. Meanwhile, 220 healthy persons matched by age and sex served as the control group. ECG indexes such as P wave dispersion (Pd), corrected QT(QTc), Tp-e and Tp-e/QT were all measured and calculated in the 1st and 72th hour. The independent sample t test and paired t test were used to compare the changes of the above indexes on the 1st day and the control group, the 1st day and the 3rd day, respectively, and the association between ECG indexes and the illness severity or adverse events (MACE) of the trauma group during hospitalization. Results:QTc, Tpec and Tp-e/QT of the acute cerebral trauma group increased on the 3rd day compared with the control group and on the first day, the differences were statistically significant ( P all <0.05). Tp-ec and Tp-e/QT in patients with moderate to severe brain injury in Glasgow Coma Scale (GCS) were increased, and the differences were statistically significant (150.48±16.58 vs 130.14±11.86, P=0.006). 0.29±0.04 vs 0.23±0.03, P=0.030). Tpec and Tp-e/QT were significantly increased in acute brain truma patients with MACE during hospitalization compared with those without MACE (149.76±12.52 vs 128.84±12.47, P <0.001). 0.30±0.04 vs 0.21±0.03,<0.001). Conclusion:Tp-e and Tp-e/QT in patients with acute cerebral trauma are correlated to the severity of the disease, which could be used as short-term prognostic indicators under certain conditions.

Objective:To investigate the therapeutic efficacy of enteral nutrition through percutaneous endoscopic gastrostomy/jejunostomy (PEG/PEJ) in patients with severe cerebral hemorrhage.Methods:Eighty-five patients with severe cerebral hemorrhage admitted to our hospital from January 2015 to December 2018 were enrolled into this retrospective study. According to ways of enteral nutrition, all 85 patients were divided into nasogastric tube group ( n=44) and PEG/PEJ tube group ( n=41). The clinical data were analyzed retrospectively, and the enteral nutrition treatment efficacy, incidence of complications, and length of hospital stays between the two groups were compared. Results:The incidences of diarrhea (14.6%, 6/41), gastric retention (34.1%, 14/41), and hypoproteinemia (26.8%, 11/41) in PEG/PEJ tube group were significantly lower than those in nasogastric tube group (38.6% [17/44], 59.1% [26/44], and 47.7% [21/44], P<0.05). However, the rate of obstruction ducts in PEG/PEJ tube group (34.1%, 14/41) was significantly higher than that in nasogastric tube group (11.4%, 5/44, P<0.05). As compared with the patients in nasogastric tube group, patients in the PEG/PEJ tube group had significantly shorter average length of hospital stays ([35.2±4.7] d vs. [37.6±5.4] d, P<0.05). The NRS2002 scores of patients in the nasogastric tube group and PEG/PEJ tube group after enteral nutrition treatment were 1.73±0.52 and 1.87±0.64, respectively, without significant difference ( P<0.05). Conclusion:The enteral nutrition treatment through PEG/PEJ could significantly reduce the incidences of diarrhea, gastric retention and hypoproteinemia, and shorten the average length of hospital stays in patients with severe cerebral hemorrhage; rate of obstruction of percutaneous endoscopic jejunostomy ducts should be reduced.