JMJD1C (Jumonji Domain Containing 1C), a member of the lysine demethylase 3 (KDM3) family, is universally required for the survival of several types of acute myeloid leukemia (AML) cells with different genetic mutations, representing a therapeutic opportunity with broad application. Yet how JMJD1C regulates the leukemic programs of various AML cells is largely unexplored. Here we show that JMJD1C interacts with the master hematopoietic transcription factor RUNX1, which thereby recruits JMJD1C to the genome to facilitate a RUNX1-driven transcriptional program that supports leukemic cell survival. The underlying mechanism hinges on the long N-terminal disordered region of JMJD1C, which harbors two inseparable abilities: condensate formation and direct interaction with RUNX1. This dual capability of JMJD1C may influence enhancer-promoter contacts crucial for the expression of key leukemic genes regulated by RUNX1. Our findings demonstrate a previously unappreciated role for the non-catalytic function of JMJD1C in transcriptional regulation, underlying a mechanism shared by different types of leukemias.
Core Binding Factor Alpha 2 Subunit/genetics* ; Humans ; Leukemia, Myeloid, Acute/pathology* ; Jumonji Domain-Containing Histone Demethylases/chemistry* ; Gene Expression Regulation, Leukemic ; Oxidoreductases, N-Demethylating/genetics* ; Cell Line, Tumor

Objective : To explore the risk factors of prognosis in patients with severe community-acquired pneumonia(SCAP) in different age groups. Methods : A multi-center and prospective study was conducted at 11 teaching hospitals in China from December 2017 to October 2021. Patients who met the criteria were assigned to the elderly group(≥65 years) and the non-elderly group(18-64 years) to demonstrate the clinical characteristics of SCAP. Patients were divided into survival group and death group according to whether they died in hospital, to determine the risk factors associated with mortality by multivariate logistic regression analysis. Results: A total of 170 patients with SCAP were included in the study. The age of SCAP was 20-93(65.75±15.23) years old, and the proportion of SCAP in the elderly was 58.82%(100/170). In-hospital mortality of non-elderly SCAP was 24.3%(17/70), and the in-hospital mortality of elderly SCAP was 28%(28/100). Compared with non-elderly group, patients in elderly group had higher severity score and more complications on admission, but the symptoms of fever and respiratory rate at admission were less obvious. In multivariable logistic regression analysis, the factors significantly associated with in-hospital mortality of non-elderly SCAP were pneumonia severity index(PSI) score(P=0.016,OR=1.022, 95%CI1.004-1.041) and invasive mechanical ventilation(P=0.037,OR=4.543, 95%CI1.092-18.898) on admission, and the risk factors associated with in-hospital mortality in elderly SCAP were sequential organ failure assessment(SOFA) score(P=0.006,OR=1.240, 95%CI1.063-1.446) and combined with coronary artery disease on admission(P=0.037,OR=2.834, 95%CI1.066-7.534). Conclusion In-hospital mortality for SCAP is high. PSI score and invasive mechanical ventilation are risk factors for in-hospital mortality of non-elderly patients with SCAP, and SOFA score and combined with coronary artery disease on admission are risk factors for in-hospital mortality of elderly patients with SCAP.

Objective:To assess the association of cytotoxic T lymphocyte-associated antigen-4 ( CTLA-4) gene polymorphisms with the prognosis of patients with Bladder urothelial carcinoma (BUC). Methods:From February 2019 to October 2020, 256 BUS patients treated at the Xinxiang Central Hospital were selected as the study group, whilst 250 healthy individuals were selected as the control group. Genotypes of rs5742909 (-318C/T), rs231775 (+ 49A/G) and rs4553808 (-1661A/G) were determined by PCR-restriction fragment length polymorphism assay. The frequencies of genotypes and alleles of the CTLA-4 gene were compared between the two groups. All patients had undergone surgical treatment and were followed up for 3 years and divided into good prognosis group ( n=166) and poor prognosis group ( n=86) based on the status of disease. The distribution of alleles and genotypes were compared, and Kaplan-Meier analysis was used to assess the association of genetic polymorphisms with the prognosis. Results:No significant difference was found in the gender, age, BMI, smoking history and alcohol use between the two groups ( P>0.05). The frequencies of GG genotype and G allele for the rs231775 (+ 49A/G) and rs4553808 (-1661A/G) loci were significantly higher in the study group compared with the control group ( P<0.05), whilst no statistical difference was found in the genotypic and allelic frequency for the rs5742909 locus between the two groups ( P>0.05). Among the 252 subjects who had completed follow-up, 86 had poor prognosis and 166 had good prognosis. The frequencies of GG genotype and G allele at the rs231775 (+ 49A/G) and rs4553808 (-1661A/G) loci were significantly lower in the good prognosis group compared with the poor prognosis group ( P<0.05). Kaplan-Meier survival curve analysis showed that the survival time of patients with GG genotype for the rs231775 (+ 49A/G) and rs4553808 (-1661A/G) loci was significantly shorter than patients with AA or AG genotypes (Log Rank 2 = 13.654, 9.974, P<0.001). Conclusion:The polymorphisms of the rs231775 and rs4553808 loci of the CTLA-4 gene are associated with genetic susceptibility and poor prognosis for BUC, and a higher GG genotypic frequency may increase the risk for infection and poor prognosis of the patients.

Objective:To investigate the risk factors for refracture after percutaneous kyphoplasty (PKP) in patients with osteoporotic vertebral compression fracture (OVCF).Methods:A retrospective cohort study was conducted on the clinical data of 149 OVCF patients who were admitted to the First Affiliated Hospital of Soochow University from June 2019 to June 2022, including 21 males and 128 females, aged 56-97 years [(73.2±8.7)years]. Initial surgical segments included T 7 in 1 patient, T 8 in 10, T 9 in 6, T 10 in 6, T 11 in 19, T 12 in 28, L 1 in 38, L 2 in 18, L 3 in 11, L 4 in 7 and L 5 in 5. Patients were divided into refracture group ( n=32) and non-refracture group ( n=117) according to whether they had postoperative refracture after PKP. Refractured surgical segments included T 8 in 2 patients, T 9 in 2, T 11 in 4, T 12 in 5, L 1 in 7, L 2 in 4, L 3 in 6, and L 5 in 2. The age, gender, underlying diseases (hypertension, diabetes), body mass index (BMI), preoperative bone mineral density (BMD), smoking history, drinking history, follow-up time, preoperative visual analogue scale (VAS), and preoperative Oswestry dysfunction index (ODI) of the two groups were recorded. Preoperative paravertebral muscle-related parameters of the two groups were calculated including cross-sectional area of bilateral psoas, bilateral erector spinae, bilateral multifidus, and vertebral bodies, paravertebral muscle mass, and vertebral bone quality (VBQ) score. Univariate analysis was performed to evaluate the correlation between the fore-mentioned indicators and postoperative refracture after PKP in OVCF patients. Multivariate logistic regression analysis was employed to identify the independent risk factors for postoperative refracture after PKP in OVCF patients. Results:Univariate analysis revealed that there was certain correlation of BMI, preoperative BMD, cross-sectional area of bilateral psoas, bilateral erector spinae, bilateral multifidus, paravertebral muscle mass and VBQ score with postoperative refracture after PKP in OVCF patients ( P<0.01), while no correlation was found between age, gender, hypertension, diabetes, smoking history, drinking history, follow-up time, preoperative VAS, preoperative ODI, or cross-sectional area of vertebral bodies and postoperative refracture after PKP in OVCF patients ( P>0.05). Multivariate logistic regression analysis showed that preoperative BMD ≤-3.4 SD ( OR=0.27, 95% CI 0.09, 0.80, P<0.05), paravertebral muscle mass ≤281.2% ( OR=0.98, 95% CI 0.97, 0.99, P<0.01) and VBQ score ≥4.8 points ( OR=4.41, 95% CI 1.18, 16.44, P<0.05) were significantly correlated with postoperative refracture after PKP in OVCF patients. Conclusion:Preoperative BMD ≤-3.4 SD, paravertebral muscle mass ≤281.2%, and VBQ score ≥4.8 points are the independent risk factors for refracture after PKP in OVCF patients.

We retrospectively analyzed the clinical data of seven patients (four men and three women) with primary hyperoxaluria (PH) type 1 (PH1) in the Department of Nephrology of Zhongda Hospital, Southeast University from January 2018 to October 2023. The mean age at disease onset was 32.1 (range: 26-42) years. The mean age at diagnosis was 40.6 (range: 28-51) years. All patients initially had kidney stones, and three patients were found to have renal insufficiency at the time of disease onset. Among them, two patients underwent hemodialysis immediately. Symptoms at the first visit included bone pain ( n=7), joint pain or deformity ( n=5), fatigue ( n=5), hypotension ( n=3), and subcutaneous nodules ( n=2). Four patients had a family history of PH. All patients had varying degrees of anemia (60-114 g/L), significant hypoalbuminemia (16.5-32.1 g/L), and hypercoagulable state (D-dimer: 2 230-12 781 μg/L). Seven patients received maintenance hemodialysis; their mean age was 37.7 (range: 26-50) years. The mean duration from disease onset to hemodialysis was 5.6 (range: 0-20) years. Five patients repeatedly experienced dialysis access dysfunction. Three patients underwent kidney transplantation before a diagnosis was made, and all transplanted kidneys lost function due to oxalate deposition. The mean follow-up duration was 14.43 (range: 4-38) months. Unfortunately, one patient died. All seven patients underwent computed tomography of the abdomen. All patients suffered skeletal abnormalities, bilateral nephrolithiasis, and nephrocalcinosis. Six patients carried AGXT gene mutations, including four compound heterozygous mutations and two pure homozygous mutations.The mutation sites included: c.823-824dup.AG (p.S275Rfs*38)(exon 8), c.815-816ins.GA (p.S275Rfs*38)(exon 8), c.595G>A (p.G199S) (exon 5), c.32C>G (p.P11R) (exon 1), and c.638C>T (p.A213V)(exon 6). According to the American College of Medical Genetics and Genomics guidelines, two loci were identified as likely pathogenic variants, seven were identified as pathogenic variants, and one locus was identified as having uncertain significance. In addition, patients 1 and 4 underwent skin biopsy, patient 2 underwent renal transplant biopsy, and patient 3 underwent bone marrow biopsy. Interestingly, significant oxalate deposition was found in the tissues. Therefore, PH1 is a rare autosomal recessive inherited disease. This study not only enhanced the understanding of the clinical characteristics of PH1 patients but also had great significance in early diagnosis and treatment of the disease.

OBJECTIVE: To testify the spatial relationship between the subscapularis muscle splitting window and the axillary nerve in modified arthroscopic Latarjet procedure, which could provide anatomical basis for the modification of the subscapularis muscle splitting. METHODS: A total of 29 adult cadaveric shoulder specimens were dissected layer by layer, and the axillary nerve was finally confirmed to walk on the front surface of the subscapularis muscle. Keeping the shoulder joint in a neutral position, the Kirschner wire was passed through the subscapularis muscle from back to front at the 4 : 00 position of the right glenoid circle (7 : 00 position of the left glenoid circle), and the anterior exit point (point A, the point of splitting subscapularis muscle during Latarjet procedure) was recorded. The vertical and horizontal distances between point A and the axillary nerve were measured respectively. RESULTS: In the neutral position of the shoulder joint, the distance between the point A and the axillary nerve was 27.37 (19.80, 34.55) mm in the horizontal plane and 16.67 (12.85, 20.35) mm in the vertical plane. CONCLUSION In the neutral position of the shoulder joint, the possibility of axillary nerve injury will be relatively reduced when radiofrequency is taken from the 4 : 00 position of the right glenoid (7 : 00 position of the left glenoid circle), passing through the subscapularis muscle posteriorly and anteriorly and splitting outward.
Adult ; Humans ; Shoulder ; Rotator Cuff/surgery* ; Arthroscopy/methods* ; Scapula/surgery* ; Shoulder Joint/surgery* ; Cadaver ; Joint Instability/surgery*

Inflammation, abnormal cholesterol metabolism, and macrophage infiltration are involved in the destruction of the extracellular matrix of the nucleus pulposus (NP), culminating in intervertebral disc degeneration (IDD). Whether nimbolide (Nim), a natural extract, can alleviate IDD is unclear. In this study, we demonstrated that Nim promotes cholesterol efflux and inhibits the activation of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by activating sirtuin 1 (SIRT1) in nucleus pulposus cells (NPCs) during inflammation. Thus, Nim balanced matrix anabolism and catabolism of NPCs. However, the inhibition of SIRT1 significantly attenuated the effects of Nim. We also found that Nim promoted the expression of SIRT1 in RAW 264.7, which enhanced the proportion of M2 macrophages by facilitating cholesterol homeostasis reprogramming and impeded M1-like macrophages polarization by blocking the activation of inflammatory signaling. Based on these results, Nim can improve the microenvironment and facilitate matrix metabolism equilibrium in NPCs. Furthermore, in vivo treatment with Nim delayed IDD progression by boosting SIRT1 expression, modulating macrophage polarization and preserving the extracellular matrix. In conclusion, Nim may represent a novel therapeutic strategy for treating IDD.

Objective:To investigate the distribution difference of pathogens among various populations and to provide a basis for clinically rational drug use.Methods:The clinical data of 1 045 patients with urinary system infections who received treatment at the Affiliated Hospital of Chengdu University from July 2021 to June 2022 was collected. The distribution characteristics of pathogenic bacteria in different populations (different ages, different genders, and different concomitant diseases) were retrospectively analyzed.Results:A total of 1 045 specimens from 1 045 patients with urinary tract infection were included in the final analysis. Among them, 743 cases were gram bacteria-positive, 205 cases were gram bacteria-negative, and 97 cases were fungi-positive. A total of 625 cases were older (aged 65 years and above) adults, accounting for 59.81%. The proportion of urine fungi-positives in the older adult population [11.68% (73/625)] was twice that of urine fungi in the young and middle-aged population (< 65 years old) [5.17% (24/420)]. Among the positive results of urine culture, older adults with diabetes mellitus accounted for the highest proportion [20.96% (219/1 045)], followed by those with urinary stones [16.08% (168/1 045)], those with hypertension [6.41% (67/1 045)], and those with chronic obstructive pulmonary disease [2.97% (31/1 045)].Conclusion:Gram-negative bacteria are the main pathogens in urine culture, followed by gram-positive bacteria and fungi. The older adults with diabetes mellitus have a higher risk of urinary tract infection compared with young and middle-aged population. The pathogenic bacteria of urinary system infection are complex, so antimicrobial drugs can be selected for targeted treatment according to the recent urine culture results to ensure the rational, safe, and effective use of drugs.

Objective:To observe the influence of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) 4 inhibitors on epithelial-mesenchymal transition (EMT) of human retinal pigment epithelial (RPE) cells induced by bevacizumab.Methods:The cultured ARPE-19 cells were divided into blank control group, bevacizumab group, bevacizumab+ VAS2870 group and bevacizumab+ GKT137831 group.Cells were cultured with 0.25 g/L bevacizumab, 0.25 g/L bevacizumab plus 3 μmol/L VAS2870 (a NOX4 inhibitor), 0.25 g/L bevaczumab plus 20 μmol/L GKT137831 (a NOX4 inhibitor) for 72 hours according to grouping.No intervention was administered to the blank control group.The mRNA and protein expression levels of NOX4 and EMT markers including fibronectin (FN), vimentin, α-smooth muscle actin (α-SMA) and tight junction related protein zonula occludens-1 (ZO-1) were measured by real-time PCR and Western blot assay, and the expression levels in different intervention groups were compared.The expressions of NOX4 and EMT markers were verified by immunofluorescence staining.Results:There were statistically significant differences in the relative mRNA and protein expression levels of FN, vimentin, α-SMA, ZO-1 and NOX4 among blank control group, bevacizumab group, bevacizumab+ VAS2870 group and bevacizumab+ GKT137831 group (mRNA: F=97.07, 195.40, 722.40, 38.56, 70.81; all at P<0.001.Protein: F=23.09, 64.58, 58.19, 26.97, 63.19; all at P<0.001). The relative mRNA and protein expression levels of FN, vimentin, α-SMA and NOX4 were significantly higher and the relative mRNA and protein expression level of ZO-1 was significantly lower in bevacizumab group than those in blank control group (all at P<0.05). The relative mRNA and protein expression levels of FN, vimentin, α-SMA and NOX4 were significantly lower and the relative mRNA and protein expression levels of ZO-1 were significantly higher in bevacizumab+ VAS2870 and bevacizumab+ GKT137831 groups than those in bevacizumab group (all at P<0.05). The immunofluorescence intensity of FN, vimentin and α-SMA was stronger and the immunofluorescence intensity of ZO-1 was weaker in bevacizumab group than blank control group.The immunofluorescence intensity of FN, vimentin and α-SMA were weaker and the immunofluorescence intensity of ZO-1 was stronger in bevacizumab+ VAS2870 group and bevacizumab+ GKT137831 group than those in bevacizumab group. Conclusions:NOX4 is involved in the bevacizumab-induced EMT of human RPE cells, the degree of which can be reduced by NOX4 inhibitors.

Objective: To compare the efficiency and biocompatibility of four different silanes on immobilizing c(RGDfK) peptide on titanium surface. Methods : After alkali-heat treatment (group OH), the titanium surface was treated with 3-aminopropyltriethoxysilane (APTES) (group OHAP), 3-chloropropyltriethoxysilane (CPTES) (group OHCP) (3-mercaptopropyltrimethoxysilane (MPTS) (group OHMPT) and 3-isobutyryloxy propyltrimethoxysilane(γ- MPS) (group OHMPS) to immobilize the c(RGDfK) cyclic peptide and constructa titanium-silane-c(RGDfK) coating. The NT group was the blank control group. The surface morphology and wettability of the coatings were detected using scanning electron microscopy and contact angle measurement. The elemental composition of the titanium surface was analyzed using X-ray photoelectron spectroscopy. After fluorescent staining with 4’,6-diamino-2-phenylindole (DAPI) and phalloidin, the adhesion of mouse preosteoblast MC3T3-E1 cells on the surface of the materials was observed using laser confocal microscopy. Cell counting kit-8 (CCK-8) and alkaline phosphatase (ALP) activity assays were used to evaluate the proliferation and osteogenic differentiation of MC3T3-E1 cells on the surface of the materials, respectively. Results : Scanning electron microscope observation showed a spongy-like 3-dimensional network formed on the titanium surface after alkali-heat treatment with silane-c(RGDfK) coating adhesion. The wettability of each group was greatly improved compared to the untreated titanium surface. The element ratios of Si/Ti and amide-N/Ti in the OHMPS group were the highest. The OHAP group exhibited the best cell adhesion effect. The cell proliferation and ALP activity of the OHAP, OHMPT, and OHMPS groups were significantly higher than the control group (P <0.05); there was no statistical difference between the OHCP group and the control group. Conclusion MPTS, CPTES and γ-MPS covalently immobilized cyclic peptide c(RGDfK) on the titanium surface, which promoted adhesion, proliferation and osteogenic differentiation of MC3T3-E1 cells. Theγ-MPS conjugated C (RGDfK)cyclic peptide exhibited the best effect. MPTS, CPTES and γ-MPS coupled with c(RGDfK) cyclic peptides had similar biological properties.