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 identify clinical risk factors for early major adverse cardiovascular events (MACEs) following surgical correction of supravalvar aortic stenosis (SVAS). Methods Patients who underwent SVAS surgical correction between 2002 and 2019 in Beijing and Yunnan Fuwai Cardiovascular Hospitals were included. The patients were divided into a MACEs group and a non-MACEs group based on whether MACEs concurring during postoperative hospitalization or within 30 days following surgical correction for SVAS. Their preoperative, intraoperative, and postoperative clinical data were collected for multivariate logistic regression. Results This study included 302 patients. There were 199 males and 103 females, with a median age of 63.0 (29.2, 131.2) months. The incidence of early postoperative MACEs was 7.0% (21/302). The multivariate logistic regression model identified independent risk factors for early postoperative MACEs, including ICU duration (OR=1.01, 95%CI 1.00-1.01, P=0.032), intraoperative cardiopulmonary bypass (CPB) time (OR=1.02, 95%CI 1.01-1.04, P=0.014), aortic annulus diameter (OR=0.65, 95%CI 0.43-0.97, P=0.035), aortic sinus inner diameter (OR=0.75, 95%CI 0.57-0.98, P=0.037), and diameter of the stenosis (OR=0.56, 95%CI 0.35-0.90, P=0.016). Conclusion The independent risk factors for early postoperative MACEs include ICU duration, intraoperative CPB time, aortic annulus diameter, aortic sinus inner diameter, and diameter of the stenosis. Early identification of high-risk populations for MACEs is beneficial for the development of clinical treatment strategies.

Objective:To evaluate the efficacy and safety of discriminative application of Chinese patent medicines in female patients after percutaneous coronary intervention (PCI) due to acute coronary syndrome (ACS).Methods:The study population was from the Chinese Patent Medicine (CPM) trial. CPM trial was a multicenter prospective cohort study, which enrolled patients from 40 centers in mainland China between February 2012 and December 2015, with the discriminative use of Chinese patent medicines as the exposure factor. Female patients with ACS after PCI who completed 36-month follow-up were included in this analysis, and were divided into a conventional treatment group (using conventional western medicine recommended by the guidelines) and a group with the discriminative use of proprietary Chinese medicines (on the basis of conventional western medicine treatment, discriminative use of Qishen Yiqi dropping pills for Qi deficiency and blood stasis syndrome, Guanxin Danshen dropping pills for blood stasis syndrome, and Danlou tablets for phlegm and blood stasis syndrome combined with the conventional western medicine). The primary endpoint event was a composite endpoint event including cardiovascular death, nonfatal myocardial infarction, and emergency revascularization surgery. Secondary endpoint events were composite endpoint events including readmission for ACS, heart failure, stroke, and other thrombotic events. Adverse events were collected. Cox proportional risk model was used to assess the effect of discriminatory application of Chinese patent medicine on endpoint events, and sensitivity analysis was performed by comparing the results with propensity score matching analysis.Results:A total of 748 female ACS post-PCI patients were included in the analysis, aged (63.2±8.3) years. There were 370 patients in the group of discriminative application of Chinese patent medicines and 378 patients in the conventional treatment group. There were 37 cases (10.0%) and 58 cases (15.3%) of primary endpoint events in the discriminatory application of Chinese patent medicines group and the conventional treatment group, respectively. Cox analysis showed that the risk of primary endpoint in the discriminatory application of Chinese patent medicines group was lower than that in the conventional treatment group after adjusting for confounding factors (adjusted HR=0.62, 95% CI 0.40-0.96, P=0.031). There were 38 (10.3%) and 57 (15.1%) cases of secondary endpoint events in the two groups, respectively. Cox regression analysis showed that the risk of secondary endpoint events in the discriminatory application of Chinese patent medicine group was lower than that in the conventional treatment group after adjusting for confounders (adjusted HR=0.56, 95% CI 0.37-0.87, P=0.001). The results of propensity score matching analysis also showed that Chinese patent medicines based on discriminatory application could reduce the risk of primary endpoint ( HR=0.62,95% CI 0.40-0.97 ,P=0.033) and second endpoint ( HR=0.56, 95% CI 0.37-0.87, P=0.009) significantly. There was no significant difference in adverse events between the two groups (12.4% (46/370) vs. 10.3% (39/378), P=0.362). Conclusion:On the basis of conventional western medicine treatment, discriminatory application of Chinese patent medicines can reduce the risk of endpoints in female patients after PCI due to ACS without significant adverse effects.

Objective:To investigate the changes in interaction proteome of NUS1 mutant R290C and their relations with pathogenicity of Lennox Gastaut syndrome (LGS). Methods:The wild-type and mutant NUS1(R290C) plasmids were constructed and transfected into human embryonic kidney HEK293T cells; 48 h after that, NUS1 protein expression in HEK293T cells was detected by Western blotting. Co-immunoprecipitation, silver nitrate staining, and proteomic analysis were used to analyze the proteins interacted with wild-type or mutant NUS1 and identify the differential interacting proteins. Enrichment analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to annotate the molecular function and signaling pathways involved in the differential proteins. DisGeNet database was used to analyze the association between differential proteins and human diseases. Protein-protein interaction (PPI) was used to analyze the interaction network of NUS1 with protein folding regulatory proteins (RTN4 and DHDDS) and developmental epileptic encephalopathy related proteins.Results:(1) There was no significant difference in NUS1 protein expression between the wild-type and mutant NUS1 transfected HEK293T cells ( t=0.536, P=0.620). (2) Compared with that with wild-type NUS1 plasmid, number of proteins interacting with mutant NUS1 plasmid was significantly reduced in the transfected cells; 310 differential interacting proteins were screened in the mutant NUS1. (3) GO and KEGG enrichment analyses showed that the differential proteins were mainly involved in protein folding reaction and translation regulation. (4) DisGeNet association analysis showed that the two most relevant proteins in the differential interacting proteins were associated with frontotemporal dementia and developmental epileptic encephalopathy. (5) PPI analysis showed that NUS1 may be involved in occurrence of neurological diseases such as LGS by affecting protein folding signaling pathways. Conclusion:NUS1 mutant R290C alters its interacting protein lineage and mediates the development of LGS and other neurological diseases probably by regulating protein folding-related signaling.

Objective:To evaluate the application effect of a personalized nutritional program based on nutrition risk screening in kidney transplant patients.Methods:Using the convenient sampling method, a total of 90 patients who completed kidney transplantation in the Second Xiangya Hospital of Central South University from November 2020 to May 2021 were selected as the research objects. Envelopes were used to draw lots, and patients were randomly divided into the control group (45 cases) and the test group (45 cases) . The control group was given routine basic treatment and nursing care, while the test group was given a personalized nutrition plan based on nutritional risk screening at basis of the control group. The changes of nutritional indexes such as total protein, albumin, prealbumin, retinol-binding protein, serum iron, total iron-binding capacity, and hemoglobin were observed before operation and on the 3rd, 7th, and 14th days after operation in the two groups. The changes of renal function indicators (such as serum creatinine level, endogenous creatinine clearance rate, glomerular filtration rate) were compared between the two groups, and the incidence of readmission within 3 months of discharge was compared between the two groups.Results:The levels of retinol-binding protein in the experimental group on the 3rd, 7th, and 14th days of intervention were better than those in the control group, while the serum creatinine level and glomerular filtration rate were lower than those in the control group, and the differences were statistically significant ( P<0.05) . On the 14th day of intervention, the levels of total protein, hemoglobin, total iron binding capacity and serum iron in the test group were higher than those in the control group, and the clearance rate of endogenous creatinine was lower than that in the control group, and the differences were statistically significant ( P<0.05) . Repeated measures analysis of variance showed that time had an effect on the recovery of nutritional and renal function indexes of patients in both groups ( P<0.05) . There were statistically significant differences in the levels of total protein, hemoglobin, retinol-binding protein, serum creatinine and the main effect of glomerular filtration rate intervention between the two groups ( P<0.05) . And there was an interaction between intervening factors and time of hemoglobin, retinol-binding protein and serum iron levels ( P<0.05) . After 3 months of follow-up, the readmission rate of patients in the experimental group was 0, and that in the control group was 13.6% (6/44) , and the difference was statistically significant ( P<0.05) . Conclusions:Nutritional risk screening combined with personalized nutrition program can effectively improve the nutritional status of kidney transplant patients, promote the recovery of transplanted kidney function, reduce the readmission rate and improve the clinical outcome of patients.

Objective:To summarize the clinical experiences of 9 ABO-incompatible kidney transplantation at our center and explore its clinical application value.Methods:Methods From April 2016 to December 2019, there were 9 living kidney transplants of ABO incompatible relatives, including type A to type B (n=3), type B to type O (n=3), type B to type A (n=1) and type AB to type B (n=2). Immunosuppressant plus single membrane plasmapheresis (PE) and/or double filtration plasmapheresis (DFPP) and rituximab were employed for pretreating recipients. Adverse reactions of recipients were observed during and after pretreatment. Blood group antibody titer, complications and other related parameters were recorded before and after transplantation before and after monitoring pretreatment.Results:After pretreatment, IgM, IgG and total titer of blood group antibodies were ≤1: 4 on the day of transplantation and the titer of non-blood group antibodies rebounded within 2 weeks (≤1: 8). During preconditioning, 2 patients experienced oral numbness and involuntary dithering during plasmapheresis and there was 1 case of infusion reaction after rituximab dosing. The early recovery of renal function was all excellent. Renal biopsy was performed in 4 patients with slow elevation of serum creatinine and 1 case developed acute antibody-mediated rejection. The survival rate of all recipients at the last follow-up was 100%.Conclusions:Live kidney transplantation of ABO-incompatible relatives is both safe and feasible so that it may help alleviate some shortage of donor kidney.

Somatic symptom disorder (SSD) is a somatic disorder characterized by excessive anxiety over various somatic symptoms for a long time, which makes patients feel very painful and the quality of personal life significantly decreased. Previous studies have shown that there is a connection between the clinical manifestations of SSD patients and their cultural background. The patient in this case report was highly affected by Chinese yin-yang culture, displaying obvious Chinese characteristics. We report a patient with SSD, whose clinical manifestations were mainly sexual dysfunction and mood symptoms which were closely related to the Traditional Chinese culture of Yin and Yang. In this case, Hamilton Anxiety Scale, Hamilton Depression Scale, and International Erectile Function Questionnaire were used to evaluate the patients ' anxiety, depression, and sexual function, and the scores were 32, 33, and 9, respectively. The patient was treated with a combination of venlafaxine and mirtazapine. After 5 weeks of treatment, the patient's clinical symptoms improved significantly. The clinical manifestations of some Chinese SSD patients have obvious characteristic relevance to Chinese theory of Yin and Yang, making SSD easily to be misdiagnosed. Therefore, clinicians should pay atlention to this situation. In addition, the combination of venlafaxine and mirtazapine may have a better effect on SSD patients with chronic pain and sexual dysfunction.

Objective To evaluate the efficacy and safety of converting traditional triple immunosuppressive regimen into quadruple immunosuppressive regimen of low-dose tacrolimus plus sirolimus plus mycophenolic acid plus hormone in expanded criteria donor (ECD) renal transplant recipients .Methods A retrospective analysis was conducted for 39 patients undergoing extended standard kidney transplantation with conversion therapy from January 2015 to June 2018 .Renal function ,liver function ,blood lipid ,bone marrow suppression ,positive rate of urinary protein ,positive rate of urinary BK virus and other adverse reactions were analyzed .Results A total of 39 recipients fulfilled the inclusion criteria ,including 28 boys and 11 girls with an average age of (37 .69 ± 11 .07) years and a median postoperative conversion time of 6 months .As compared with pre-conversion therapy ,renal function and estimated glomerular filtration rate improved significantly at 1 month ,3 months ,6 months and 1 year (P<0 .05) .No significant difference existed in the level of blood lipid ,whole blood leukocyte or hemoglobin at pre and post-conversion ( P>0 .05) .No significant difference existed between AST and ALT at pre and post-conversion (P< 0 .05) . After conversion , the positive rates of urinary protein and BK virus urine declined . Subacute rejection occurred in 1 case after conversion .Addition of sirolimus was curative .No severe adverse reactions such as infection and diarrhea occurred in the remaining cases .Conclusions T he quadruple immunosuppressive regimen of low-dose tacrolimus plus sirolimus plus mycophenolic acid and hormone is both safe and effective for ECD recipients of renal transplantation .

Objective To explore expression level of circulating microRNA (miR)-133a and Galectin-3 and their potential clinical application in differential diagnosis between patients with chronic Keshan disease and dilated cardiomyopathy.Methods Twenty-eight patients with chronic Keshan disease and 28 cases of age-and sex-matched healthy people as control from the same severe historical endemic areas of Keshan disease in Heilongjiang Province,and another 28 patients with dilated cardiomyopathy from non-affected areas were chosen for the study.All the subjects were asked for disease history and did physical examination,examined by Doppler echocardiography for left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD),and collected fasting venous blood specimen (elbow vein).The plasma miR-133a and the serum Galectin-3 were determined by Real-time PCR and enzyme-linked immunosorbent method,respectively.Meanwhile,the correlation was analyzed between miR-133a,galectin-3,LVEF and LVEDD.Results The miR-133a and Galectin-3 levels in different groups were statistically different (F =48.789,9.485,P ＜ 0.01).The plasma miR-133a level in chronic Keshan disease group and dilated cardiomyopathy group [median (quartile):0.394 (0.271,0.770),1.665 (0.943,2.713)] were both significantly lower than those in control group [2.382 (1.502,3.302],P ＜ 0.01 or ＜ 0.05],and the plasma miR-133a level in chronic Keshan disease group was lower than that in dilated cardiomyopathy group (P ＜ 0.01).There was no significant difference of serum Galectin-3 level between chronic Keshan disease group and dilated cardiomyopathy group [17.710 (9.624,27.799),12.692 (9.376,26.290) μg/L,P ＞ 0.05],but both were significantly higher than those in control group [8.070 (7.135,9.308) μg/L,P ＜ 0.01].The miR-133a was positively correlated with LVEF (rs =0.297,P ＜ 0.01),while negatively correlated with LVEDD,and Galectin-3 (rs =-0.271,-0.318,P ＜ 0.05 or ＜ 0.01);the serum Galectin-3 was negatively correlated with LVEF (rs =-0.392,P ＜ 0.01),and positively correlated with LVEDD (rs =0.385,P ＜ 0.01).Conclusion The combined application of miR-133a,Galectin-3,LVEF and LVEDD may provide assistance in clinical differential diagnosis of chronic Keshan disease and dilated cardiomyopathy.

Objective: To study the correlation between low back pain (LBP) and occupational stress in coal miners. Methods: From January 2015 to December 2016, a total of 472 front-line workers in a mining area of a large-scale coal mining enterprise in Shanxi, China were enrolled in the study. The general information, condition of LBP, and occupational stress level of the subjects were obtained by questionnaire survey. Dichotomous logistic regression (DLR) was used to analyze the correlation between LBP and occupational stress. Results: Of the 472 subjects, 186 subjects experienced LBP in the past year; the prevalence rate of LBP was 39.41%. The scores of the Occupational Role Questionnaire were significantly higher for workers in the LBP group than in the non-LBP group (P<0.01) . As revealed by the DLR analysis, age, marital status, length of service, occupational stress role, labor intensity, keeping single posture during work, and working in shifts were risk factors of LBP (P<0.01) , while smoking may be a protective factor against LBP (P<0.01) . Conclusion Occupational stress role is a potential risk factor for LBP in coal miners (P<0.01) . Reasonable work assignment and timely alleviation of occupational stress may be one of the effective approaches to prevent LBP.