Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Objective:To investigate the clinical phenotype and genetic variation of Basel-Vanagaite-Smirin-Yosef syndrome (BVSYS), and to enhance clinicians′ knowledge of the disease.Methods:The clinical data of a child with BVSYS admitted to the Department of Neurological Rehabilitation, Qingdao Women and Children′s Hospital Affiliated to Qingdao University in February 2023 were collected. Whole genome sequencing was used to analyze the pathogenic genes of the child, and Sanger sequencing was used to verify the suspected mutation sites of the family members. The clinical phenotype and genetic variation characteristics were analyzed, and the clinical characteristics of BVSYS were summarized in combination with relevant literature.Results:The patient, a female aged 3 years and 1 month, presented with global developmental delay, speech disorder, distinctive facial features, esotropia, epilepsy, hypotonia and atrial septal defect. Brain magnetic resonance imaging revealed bilateral ventriculomegaly with abnormal signal intensity in the posterior bodies of both lateral ventricles and thinning of the corpus callosum. The whole genome sequencing revealed a homozygous missense mutation c.518 (exon5) T>C (p.IIe173Thr) in the MED25 gene of the child, and Sanger sequencing confirmed that her parents and elder brother carried the aforementioned heterozygous mutation, which was classified as a likely pathogenic mutation according to the guidelines of the American College of Medical Genetics and Genomics. A total of 22 cases from 6 literature sources were retrieved, with no reported cases in China so far. Conclusions:BVSYS is clinically rare. For patients presenting with unexplained global developmental delay or intellectual disability combined with craniofacial, neurological, cardiac, and eye abnormalities, targeted genetic testing can facilitate a definite diagnosis.

Objective:To translate the Pediatric Epilepsy-Specific Health-Related Quality of Life (PedsQL TM Epilepsy Module) into Chinese and test its reliability and validity in children aged 5 to 7 years old and their parents. Methods:Brislin translation model was used for forward translation, back translation, harmonization, and proofreading of the PedsQL TM Epilepsy Module. Chinese version of PedsQL TM Epilepsy Module beta version was developed through cognitive interviews, expert consultations, and pre-surveys for cross-cultural adaptation of the scale. From April to November 2023, convenience sampling was used to select 420 children with epilepsy and their parents admitted to the Children's Hospital of Soochow University as participants for a questionnaire survey to test its reliability and validity. Results:A total of 840 questionnaires were distributed (420 for children and 420 for parents), and 394 valid questionnaires were collected from children and 400 valid questionnaires were collected from parents, and the effective response rates of the questionnaires were 93.81% (394/420) and 95.24% (400/420), respectively. Chinese version of PedsQL TM Epilepsy Module (child report version) included five dimensions and 28 items. Chinese version of PedsQL TM Epilepsy Module (parent agent report version) consisted of five dimensions and 29 items. The content validity indices at the item level were 0.800 to 1.00, while the content validity indices at the scale level were 0.978 and 0.979, respectively. Exploratory factor analysis of two versions of the scale showed that five common factors were extracted, with cumulative variance contribution rates of 64.557% and 75.205%, respectively. Confirmatory factor analysis showed that the models of the two scales fitted well. The total Cronbach's α coefficients of the two scales were 0.906 and 0.914, respectively, with Cronbach's α coefficients for each dimension ranging from 0.869 to 0.991. The total test-retest reliability coefficients of the scale were 0.998 and 0.995, respectively, and the test-retest reliability coefficients of each dimension were 0.803 to 0.995. Conclusions:Chinese version of the PedsQL TM Epilepsy Module has good reliability and validity, and is suitable for evaluating the health-related quality of life of children with epilepsy aged 5 to 7 years old in China.

Objective:To investigated the safety and efficacy of donor-derived CD19+ or sequential CD19+ CD22+ chimeric antigen receptor T-cell (CAR-T) therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:The data of 22 patients with B-ALL who relapsed after allo-HSCT and who underwent donor-derived CAR-T therapy at the Zhujiang Hospital of Southern Medical University and the 920th Hospital of Joint Logistics Support Force of the People’s Liberation Army of China from September 2015 to December 2022 were retrospectively analyzed. The primary endpoint was overall survival (OS), and the secondary endpoints were event-free survival (EFS), complete remission (CR) rate, and Grade 3-4 adverse events.Results:A total of 81.82% ( n=18) of the 22 patients achieved minimal residual disease-negative CR after CAR-T infusion. The median follow-up time was 1037 (95% CI 546–1509) days, and the median OS and EFS were 287 (95% CI 132-441) days and 212 (95% CI 120-303) days, respectively. The 6-month OS and EFS rates were 67.90% (95% CI 48.30%-84.50%) and 58.70% (95% CI 37.92%-79.48%), respectively, and the 1-year OS and EFS rates were 41.10% (95% CI 19.15%-63.05%) and 34.30% (95% CI 13.92%-54.68%), respectively. Grade 1-2 cytokine release syndrome occurred in 36.36% ( n=8) of the patients, and grade 3-4 occurred in 13.64% of the patients ( n=3). Grade 2 and 4 graft-versus-host disease occurred in two patients. Conclusion:Donor-derived CAR-T therapy is safe and effective in patients with relapsed B-ALL after allo-HSCT.

Objective:To investigate the relationship between metabolic syndrome and 1-year poor outcome in elderly patients with acute cerebral infarction (ACI).Methods:The clinical data of elderly patients with ACI admitted to Renqiu Kangjixintu Hospital from January 2014 to November 2018 were selected and divided into metabolic syndrome group (931 cases) and non-metabolic syndrome group (1 851 cases). The clinical data of the two groups of elderly patients with ACI were compared, and the effect of metabolic syndrome on poor outcome (modified Rankin scale>2 scores) of elderly patients with ACI in 1 year was analyzed by multivariate Logistic regression.Results:The proportion of female, hypertension, diabetes, hyperlipidemia, coronary heart disease, smoking, excessive alcohol consumption and antiplatelet drug use in the metabolic syndrome group were higher than those in the non-metabolic syndrome group: 52.74%(491/931) vs. 32.58%(603/1 851), 79.16%(737/931) vs. 64.29% (1 190/1 851), 42.32% (394/931) vs. 6.43% (119/1 851), 17.19% (160/931) vs. 11.62% (215/1 851), 18.90% (176/931) vs. 14.10% (261/1 851), 62.73% (584/931) vs. 50.89% (942/1 851), 3.73% (69/931) vs. 1.61% (15/1 851), 19.23% (179/931) vs. 15.51% (287/1 851), the levels of body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose (FPG), fasting plasma glucose (TG), total cholesterol (TC), platelet (PLT), fibrinogen (FIB), fall score were higher than those in non-metabolic syndrome group: 26.67 (25.31, 28.60) kg/m 2 vs. 23.30 (21.48, 24.91) kg/m 2, (167.17 ± 22.96) mmHg (1 mmHg = 0.133 kPa) vs. (164.21 ± 24.90) mmHg, (87.06 ± 13.10) mmHg vs. (85.76 ± 12.99) mmHg, (7.33 ± 2.64) mmol/L vs. (5.35 ± 1.38) mmol/L, (2.12 ± 1.51) mmol/L vs. (1.13 ± 0.78) mmol/L, (4.97 ± 1.31) mmol/L vs. (4.65 ± 0.99) mmol/L, 213.00 (179.00, 256.00) × 10 9/L vs. 203.00 (172.00, 241.00) × 10 9/L, 3.07 (2.63, 3.52) g/L vs. 2.94 (2.55, 3.37) g/L, (6.12 ± 1.70) scores vs. (5.93±1.74) scores, the levels of age, high density lipoprotein cholesterol (HDL-C), homocysteine (Hcy) and pressure ulcer score were lower than those of non-metabolic syndrome group: (69.29 ± 6.96) years vs. (71.28 ± 7.66) years, (0.98 ± 0.34) mmol/L vs. (1.31 ± 0.88) mmol/L, (18.93 ± 13.07) mmol/L vs. (21.66 ± 16.39) mmol/L, (18.55 ± 2.42) vs. (19.02 ± 2.43), with statistical significance ( P<0.05). After 1-year follow-up, the proportion of poor outcomes in the metabolic syndrome group was higher than that in the non-metabolic syndrome group: 21.70%(202/931) vs. 18.69% (346/1 851), with statistical significance ( P<0.05). Multivariate Logistic regression analysis showed that age, stroke, national institutes of health stroke scale (NIHSS) score at admission, systolic blood pressure, Hcy, pressure ulcer score, fall score, metabolic syndrome were independent risk factors for poor outcome of ACI in 1 year ( OR = 1.056, 1.309, 1.138, 1.005, 1.006, 0.882, 1.076 and 1.285; 95% CI 1.040 to 1.072, 1.037 to 1.652, 1.097 to 1.180, 1.000 to 1.010, 1.000 to 1.013, 0.834 to 0.933, 1.004 to 1.152 and 1.001 to 1.657; P<0.05). Conclusions:Multiple risk factors for stroke are closely related to poor outcome of ACI in the elderly. And metabolic syndrome is an independent risk factor for poor outcome of ACI in the elderly in 1 year.

OBJECTIVE: To investigate the effect of interleukin-17A (IL-17A) on chemosensitivity of ovarian cancer cells to cisplatin (DDP) and explore the mechanism in light of autophagy regulation. METHODS: Ovarian cancer SKOV3 cells cultured RESULTS: DDP increased the expression of IL-17RA in ovarian cancer SKOV3 cells. Treatment with IL-17A significantly reduced the susceptibility of SKOV3 cells to cisplatin-induced apoptosis ( CONCLUSIONS IL-17A/IL-17RA can decrease chemosensitivity of SKOV3 cells to DDP by upregulating DDP-induced autophagy.
Antineoplastic Agents/therapeutic use* ; Apoptosis/drug effects* ; Autophagy/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Cisplatin/pharmacology* ; Drug Resistance, Neoplasm/drug effects* ; Female ; Humans ; Interleukin-17/pharmacology* ; Ovarian Neoplasms/drug therapy* ; Receptors, Interleukin-17

Objective To assess the clinical diagnostic value of sputum fungal culture combined with serum galactomannan (GM) antigen detection in patients with invasive pulmonary aspergillosis (IPA). Methods A total of 567 cases, because of respiratory symptoms and/or suspected aspergillosis infection, admitted into the Affiliated Hospital of Jining Medical University from January to December 2016 were enrolled, the positive rate of pulmonary aspergillosis infection was determined by sputum culture and serum GM test, the values of single sputum culture and the combination of the culture and GM test for diagnosis of IPA were analyzed, and the differences in the positive rates of pulmonary aspergillus determined by GM test and traditional methods [chest computed tomography (CT), sputum culture and blood culture] were compared. At the same time, when fever patients had treated for 3-4 days, the results were ineffective, antifungal therapy was applied according to the disease condition and the results of auxiliary examinations (chest CT, sputum culture and GM test), and the effect of antifungal therapy was observed. Results The serum GM test was positive in 85 cases, and sputum fungal culture was positive in 226 cases, there were 108 cases presenting positive and 148 cases negative in both culture and GM test; the diagnosis of IFD was confirmed in 186 cases (32.8%), clinical diagnosis was made in 107 (18.9%) cases, suspected in 131 (23.1%) cases and excluded in 143 cases (25.2%). Compared with single sputum fungal culture, the sensitivity [98.2% (108/110) vs. 20.4% (46/226)], specificity [85.1% (148/174) vs. 45.1% (148/328)], positive predictive value [80.6% (108/134) vs. 37.1% (46/124)] and negative predictive value [98.1% (148/151) vs. 63.0% (148/235)] of combination method of GM test and sputum fungal culture for diagnosis of IPA were obviously higher; the positive rate of GM test for the detection of pulmonary aspergillus infection was significantly higher than that of traditional methods of chest CT, sputum culture and blood culture [64.7% (55/85) vs. 35.7% (35/98), 20.4% (46/226), 4.8% (14/292)], and the GM value being 0.5 as the positive critical value for the diagnosis of IPA can provide desirable sensitivity and specificity. In this study, 186 patients with pulmonary aspergillus infection had completed the antifungal treatment. The effective rates of antifungal treatment 1, 2, 3 and 6 months after treatment were not significantly changed with the prolongation of the therapeutic time [75.4% (135/179), 77.1% (111/144), 77.2% (31/79), 82.6% (19/23)], but the contents of serum GM was significantly lowered compared with that before treatment [absorbance (A) value: 0.49±0.03, 0.46±0.03, 0.39±0.03, 0.23±0.03 vs. 0.56±0.03, all P < 0.05], the number of positive cases was also decreased (186, 179, 144, 79, 23 respectively), so dynamic GM tests can help observe the therapeutic effect. Conclusion The study results showed: serum GM antigen detection combined with sputum fungal culture can significantly improve the clinical diagnostic efficiency for patients with pulmonary aspergillus infection.

Objective To investigate the effects of low-fat diet or statin intervention at early age on brain amyloid β-protein (Aβ) pathology and behaviors of middle-aged Tg2576 mice.Methods Thirty-five two-month-old Tg2576 mice were randomly divided into following 5 groups:a juvenile statin group,a juvenile low-fat diet group,a young statin group,a young low-fat group,and a blank control group (n=7);mice in the low-fat diet groups were given standard low-fat feed,and mice in the statin group were given atorvastatin at 17 mg/(kg· d) into the normal diet.The initiation times of intervention were,respectively,set to be 2-month-old in juvenile groups and 6-month-old in young groups;meanwhile,mice in the blank-control group were fed with normal diet without statin.All mice were raised to be 10-month-old and tested by Morris water maze for evaluating cognitive behaviors two weeks before execution.After peripheral blood and brains being taken,a monoclonal anti-Aβ42 antibody was employed to immunostain mice brain paraffin tissue sections for assaying tissue Aβ plaque immunoreactivity (TAPIR),and the levels of Aβ40,Aβ42,β-secretase,and γ-secretase in homogenates were detected by enzyme-linked immunosorbent assays (ELISA).Results As compared with those in the blank-control group,the average escape latencies,times of passing through hidden platforms,percentage of strong TAPIR,Aβ42 and γ-secretase level in all intervention groups showed no statistical differences (P＞0.05).As compared with those in the blank control group,Aβ42 in homogenates of young intervention groups and β-secretase level in the young statin group were significantly higher (P＜0.05).Conclusion Interventions initiated from juvenile or young,and low-fat diet intervention or statin intervention can neither improve the mice's Morris water maze testing results,nor reduce Aβs burdens in brain homogenates and Aβ40 immunopathologies in brain tissues of middle-aged mice;over early initiation of low-fat diet intervention or statin intervention might accelerate or worsen Alzheimer's disease progress.

Objecve To observe the clinical effect and safety of the Chinese medicine syndrome differentiation combined with HAART for the ADC(acquried immune deficiency syndrom dementia complex). Methods A total of 80 patients with ADC were divided into the treatment group and control group based on random number table, 40 in each group. The patients in the control group were treated by highly active anti-retrovital therapy (HAART). The patients in the treatment group were treated with TCM treatment on the based of the control group. Both groups received the treatment for 3 months.These outcomes were measured: TCM syndrome integral, mini mental state examination(MMSE), daily behavior scale(ADL), change of clinical stage, and adverse reactions. Results The effect rate of treatment group was 82.5%, which was significant higher than 65% of the control group (χ2=8.115,P=0.024). After the treatment, the ADL integral of the treatment group (37.69 ± 5.31vs.33.67 ± 5.16;t=2.528,P=0.021) was significantly higher than that before the treatment; and the ADL integral of the control group(36.96 ± 5.52vs.34.54 ± 4.98;t=2.747,P=0.027) was significantly higher than that before the treatment.But there was no significant difference between the two groups after the treatment (t=2.003,P=0.139). After the treatment, the MMSE integral of the treatment group (24.76 ± 4.43 vs.19.97 ± 5.46;t=1.006,P=0.013) was significantly higher than that before the treatment; the MMSE integral of the control group(24.65 ± 4.36 vs. 20.11 ± 4.87;t=1.035,P=0.014) was significantly higher than that before the treatment. But there was no significant difference between the two groups after the treatment (t=0.953, P=0.347).There was no significant difference between the two groups in the clinical stage change (phase1χ2=1.231,P=0.954; phase2χ2=2.726,P=1.053). There was no adverse reaction in the two groups during the treatment.Conclusions The Traditional Chinese medcine combined with HAART was better than HAART alonein the treatment of ADC.