Hydroxychloroquine-induced hyperpigmentation of the skin and bull's-eye maculopathy in rheumatic patients: a case report and literature review.

Hydroxychloroquine (HCQ) is used as a traditional disease-modifying antirheumatic drugs (DMARDs), for the treatment of autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, it can cause serious adverse reactions, including hyperpigmentation of the skin and bull's-eye macular lesions. Here, we present a case of HCQ-induced hyperpigmentation of the skin and bull's-eye macular lesions in a patient who received HCQ for RA. A 65-year-old female patient developed blurred vision and hyperpigmentation of multiple areas of skin over the body for one month after 3 years of HCQ treatment for RA. Based on clinical presentation, ophthalmological examination and dermatopathological biopsy, a diagnosis of drug-induced cutaneous hyperpigmentation and bullous maculopathy of the right eye was made. After discontinuation of HCQ and treatment with iguratimod tablets, the hyperpigmentation of the patient 's skin was gradually reduced, and the symptoms of blurred vision were not significantly improved. We also reviewed the available literature on HCQ-induced cutaneous hyperpigmentation and bull's-eye macular lesions and described the clinical features of HCQ-induced cutaneous hyperpigmentation and bull's-eye macular lesions. In conclusion, clinicians should be aware of early cutaneous symptoms and HCQ-associated ophthalmotoxicity in patients with rheumatic diseases on HCQ sulphate and should actively monitor patients, have them undergo regular ophthalmological examinations and give appropriate treatment to prevent exacerbation of symptoms.

Metabolism pathway-based subtyping in endometrial cancer: An integrated study by multi-omics analysis and machine learning algorithms.

Endometrial cancer (EC), the second most common malignancy in the female reproductive system, has garnered increasing attention for its genomic heterogeneity, but understanding of its metabolic characteristics is still poor. We explored metabolic dysfunctions in EC through a comprehensive multi-omics analysis (RNA-seq datasets from The Cancer Genome Atlas [TCGA], Cancer Cell Line Encyclopedia [CCLE], and GEO datasets; the Clinical Proteomic Tumor Analysis Consortium [CPTAC] proteomics; CCLE metabolomics) to develop useful molecular targets for precision therapy. Unsupervised consensus clustering was performed to categorize EC patients into three metabolism-pathway-based subgroups (MPSs). These MPS subgroups had distinct clinical prognoses, transcriptomic and genomic alterations, immune microenvironment landscape, and unique patterns of chemotherapy sensitivity. Moreover, the MPS2 subgroup had a better response to immunotherapy. Finally, three machine learning algorithms (LASSO, random forest, and stepwise multivariate Cox regression) were used for developing a prognostic metagene signature based on metabolic molecules. Thus, a 13-hub gene-based classifier was constructed to predict patients' MPS subtypes, offering a more accessible and practical approach. This metabolism-based classification system can enhance prognostic predictions and guide clinical strategies for immunotherapy and metabolism-targeted therapy in EC.

Formation of dentinal microcracks after root canal preparation with four kinds of mechanical nickel-titanium files.

OBJECTIVES: This study aimed to compare the differences among four kinds of mechanical Ni-Ti files including T-Flex, Reciproc Blue (RB), ProTaper Gold (PTG), and ProTaper Universal (PTU) in dentinal microcrack generation after root canal preparation in vitro by using micro-computed tomography (micro-CT) analysis. METHODS: A total of 32 freshly extracted double-root-canal premolars with an angle not exceeding 10° were selected and established as root canal preparation models in vitro. Then, the specimens were randomly assigned to four experimental groups (n=8) according to the different Ni-Ti systems used for root canal preparation: group T-Flex, group RB, group PTG, and group PTU. The voxel size of the micro-CT was set at 17.18 µm. Pre- and post-operative cross-sectional images of roots (n=56 940) were scanned and analyzed to identify the presence of dentinal microcracks. The results of each group were expressed by the quantity and percentage of sectional images with microcracks. McNemar test was used to determine whether a significant difference existed in the existence of dentinal microcracks before and after instrumentation. The level of significance was set at P<0.05. RESULTS: Overall, 11.04% of the images presented dentinal defects (n=6 288). Dentinal microcracks were observed in 9.82%, 10.79%, 12.27%, and 11.25% of the post-instrumentation images from groups T-Flex, RB, PTG, and PTU, respectively. However, all these dentinal microcracks were already present in the corresponding pre-operative images. No new microcrack of premolars were generated after the root canal preparation utilizing the aforementioned systems. CONCLUSIONS: Denti-nal microcracks already existed in advance in extracted teeth before root canal preparation. Root canal preparation using the T-Flex, RB, PTG, and PTU systems did not induce the formation of new dentinal microcracks on the straight root canals of premolars.

Mesh-less laparoscopic extraperitoneal linear suspension treatment of vaginal vault prolapse.

OBJECTIVES: To report the results of a mesh-less laparoscopic extraperitoneal linear suspension technique for the treatment of post-hysterectomy vaginal vault prolapse (PHVP). STUDY DESIGN: A retrospective observational study was conducted collecting medical records of 41 patients with symptomatic PHVP treated between November 2017 to November 2019 in Gynecologic department of China-Japan Friendship Hospital. All patients had Pelvic Organ Prolapse Quantification (POP-Q) scores indicating stage 3-4 PHVP and underwent mesh-less laparoscopic extraperitoneal linear suspension.The primary outcome was the subjective satisfaction rate based on responses to validated questionnaires. The secondary outcomes were the objective anatomical cure rate based on POP-Q scores and complication rates. All listed parameters were determined before the surgery and at control examinations in 1 year and 3 years after the treatment. RESULTS: The operation was completed successfully without serious complications in all patients. Mean operation time was 53.8 mins. Comparison of the scores by the questionnaires revealed a significant improvement in the quality of life in the postoperative period.The subjective satisfaction rates were 100 % (41/41) and 95 % (38/40) at 1 year and 3 years after surgery. The objective cure rates were 100 % (41/41) and 97.5 % (39/40) at 1 year and 3 years after surgery, respectively. During the follow-up, none of the patients experienced suture exposure, infection, chronic pelvic pain, or other related complications. CONCLUSION: The mesh-less laparoscopic extraperitoneal linear suspension technique avoids the use of implantable synthetic mesh. It has been shown to lead to favorable postoperative outcomes, considerable patient contentment, and low complication rates. It offers a new, cost-effective treatment option for PHVP patients.

In situ electrochemical potential-induced synthesis of metal organic framework membrane on polymer support for H2/CO2 separation.

Metal-Organic Framework (MOF) membranes act as selective layers have offered unprecedented opportunities for energy-efficient and cost-effective gas separation. Searching for the green and sustainable synthesis method of dense MOF membrane has received huge attention in both academia and industry. In this work, we demonstrate an in situ electrochemical potential-induced synthesis strategy to aqueously fabricate Metal Azolate Framework-4 (MAF-4) membranes on polypropylene (PP) support. The constant potential can induce the heterogeneous nucleation and growth of MAF-4, resulting an ultrathin membrane with the thickness of only 390 nm. This high-quality membrane exhibits a high H2/CO2 separation performance with the H2 permeance as high as 1565.75 GPU and selectivity of 11.6. The deployment of this environment friendly one-step fabrication method under mild reaction conditions, such as low-cost polymer substrate, water instead of organic solvent, room temperature and ambient pressure shows great promise for the scale-up of MOF membranes.

Bioactive 5/5/5/6 Four-Ring System Iridoids from Plumeria alba L.

Two rare 5/5/5/6 four-ring system iridoids, allamancins A and B (1 and 2) together with one known biogenetically related iridoid derivative, 3-O-methyallamancin (3) were isolated from the flowers of Plumeria alba L. The structures of these iridoid derivatives were determined by comprehensive spectroscopic analyses. The absolute configuration of 1 was confirmed by X-ray crystallographic analysis. The inhibitory activities of compounds 1-3 against nitric oxide (NO) production induced and three cancer cell lines were evaluated in vitro. Compounds 1 and 3 showed inhibitory activities on NO production with IC50 values of 18.3±0.12 and 22.1±0.14 µM, respectively. Compounds 1-3 showed moderate inhibitory activities against cancer cell lines of A549, Hela and MCF-7.

Citrisorbicillinol, an undescribed hybrid sorbicillinoid with osteogenic activity from Penicillium citrinum ZY-2.

Citrisorbicillinol (1), along with six other known compounds (2-7), was isolated from an endphyte Penicillium citrinum ZY-2 of Plantago asiatica L. Citrisorbicillinol (1) was characterized as a skeletally unprecedented hybrid sorbicillinoid, and its unique framework is likely formed by intermolecular [4 + 2] cycloaddition between intermediates derived from citrinin and sorbicillinoid biosynthetic gene clusters. Compounds 1 and 2 demonstrated to promote osteoblastic differentiation in MC3T3-E1 cells, and to be osteogenic in the prednisolone induced osteoporotic zebrafish. Compounds 3-7 exhibited moderate cytotoxicity against four human cancer cell lines.

A robust and validated LC-MS/MS method for the quantification of ramucirumab in rat and human serum using direct enzymatic digestion without immunoassay.

A new liquid chromatography tandem mass spectrometry (LC-MS/MS) method was established to quantify the anti-gastric cancer fully human monoclonal antibody (ramucirumab) in rat and human serum. The surrogate peptide (GPSVLPLAPSSK) for ramucirumab was generated by trypsin hydrolysis and quantified using the isotopically labeled peptide GPSVLPLAPSSK[13C6, 15N2]ST containing two more amino acids at the carboxyl end as an internal standard to correct for variations introduced during the enzymatic hydrolysis process and any mass spectrometry changes. Additionally, the oxidation and deamidation of unstable peptides (VVSVLTVLHQDWLNGK and NSLYLQMNSLR) were detected. The quantitative range of the proposed method was 1-1000 µg/mL, and complete methodological validation was performed. The precision, accuracy, matrix effect, sensitivity, stability, selectivity, carryover, and interference of the measurements met the required standards. The validated LC-MS/MS method was applied to pharmacokinetic studies in rats administered ramucirumab at 15 mg/kg intravenously. Overall, a robust, efficient, and cost-effective LC-MS/MS method was successfully developed for quantifying ramucirumab in rat and human serum.

Multi-omic approaches provide insights into the molecular mechanisms of Sojae semen germinatum water extract against overactive bladder.

Sojae semen germinatum (SSG) is derived from mature soybean seeds that have been germinated and dried, typically with sprouts measuring approximately 0.5 cm in length. SSG is traditionally known for its properties in clearing heat and moisture. Nevertheless, limited information was reported on the effects and mechanisms of SSG in alleviating urinary symptoms. This study employed urodynamic parameters to investigate the therapeutic effect of SSG water extract on overactive bladder (OAB) in the rat model with benign prostatic hyperplasia. Through a combination of transcriptomic and metabolomic analyses, the pathways and key proteins of the SSG treatment for OAB were identified and validated by ELISA and Western blotting. Furthermore, network pharmacology elucidated the roles of SSG's isoflavones acting on the target which was identified by above-mentioned multi-omics analysis. Our results indicate that SSG water extract significantly mitigated OAB by down-regulating the PGE2/EP1/PLCß2/p-MLC signaling pathway. It was speculated that the active ingredient in the SSG on EP1 was genistein. This study provided valuable insights into the molecular mechanisms of SSG water extract, emphasizing the multi-target characteristics and critical pathways in improving OAB. Furthermore, this study contributes to the potential utilization of SSG as a functional food.

Correlation between the expressions of metastasis-associated factor-1 in colon cancer and vacuolar ATP synthase.

BACKGROUND: Clinical prognosis often worsens due to high recurrence rates following radical surgery for colon cancer. The examination of high-risk recurrence factors post-surgery provides critical insights for disease evaluation and treatment planning. AIM: To explore the relationship between metastasis-associated factor-1 in colon cancer (MACC1) and vacuolar ATP synthase (V-ATPase) expression in colon cancer tissues, and recurrence rate in patients undergoing radical colon cancer surgery. METHODS: We selected 104 patients treated with radical colon cancer surgery at our hospital from January 2018 to June 2021. Immunohistochemical staining was utilized to assess the expression levels of MACC1 and V-ATPase in these patients. RESULTS: The rates of MACC1 and V-ATPase positivity were 64.42% and 67.31%, respectively, in colon cancer tissues, which were significantly higher than in paracancerous tissues (P < 0.05). Among patients with TNM stage III, medium to low differentiation, and lymph node metastasis, the positive rates of MACC1 and V-ATPase were significantly elevated in comparison to patients with TNM stage I-II, high differentiation, and no lymph node metastasis (P < 0.05). The rate of MACC1 positivity was 76.67% in patients with tumor diameters > 5 cm, notably higher than in patients with tumor diameters ≤ 5 cm (P < 0.05). We observed a positive correlation between MACC1 and V-ATPase expression (rs = 0.797, P < 0.05). The positive rates of MACC1 and V-ATPase were significantly higher in patients with recurrence compared to those without (P < 0.05). Logistic regression analysis revealed TNM stage, lymph node metastasis, MACC1 expression, and V-ATPase expression as risk factors for postoperative colon cancer recurrence (OR = 6.322, 3.435, 2.683, and 2.421; P < 0.05). CONCLUSION: The upregulated expression of MACC1 and V-ATPase in colon cancer patients appears to correlate with clinicopathological features and post-radical surgery recurrence.

Split complementation of base editors to minimize off-target edits.

Base editors (BEs) empower the efficient installation of beneficial or corrective point mutations in crop and human genomes. However, conventional BEs can induce unpredictable guide RNA (gRNA)-independent off-target edits in the genome and transcriptome due to spurious activities of BE-enclosing deaminases, and current improvements mostly rely on deaminase-specific mutagenesis or exogenous regulators. Here we developed a split deaminase for safe editing (SAFE) system applicable to BEs containing distinct cytidine or adenosine deaminases, with no need of external regulators. In SAFE, a BE was properly split at a deaminase domain embedded inside a Cas9 nickase, simultaneously fragmenting and deactivating both the deaminase and the Cas9 nickase. The gRNA-conditioned BE reassembly conferred robust on-target editing in plant, human and yeast cells, while minimizing both gRNA-independent and gRNA-dependent off-target DNA/RNA edits. SAFE also substantially increased product purity by eliminating indels. Altogether, SAFE provides a generalizable solution for BEs to suppress off-target editing and improve on-target performance.

Assessment of left atrioventricular coupling and left atrial function impairment in diabetes with and without hypertension using CMR feature tracking.

PURPOSE: The study was designed to assess the effect of co-occurrence of diabetes mellitus (DM) and hypertension on the deterioration of left atrioventricular coupling index (LACI) and left atrial (LA) function in comparison to individuals suffering from DM only. METHODS: From December 2015 to June 2022, we consecutively recruited patients with clinically diagnosed DM who underwent cardiac magnetic resonance (CMR) at our hospital. The study comprised a total of 176 patients with DM, who were divided into two groups based on their blood pressure status: 103 with hypertension (DM + HP) and 73 without hypertension (DM-HP). LA reservoir function (reservoir strain (εs), total LA ejection fraction (LAEF)), conduit function (conduit strain (εe), passive LAEF), booster-pump function (booster strain (εa) and active LAEF), LA volume index (LAVI), LV global longitudinal strain (LVGLS), and LACI were evaluated and compared between the two groups. RESULTS: After adjusting for age, sex, body surface area (BSA), and history of current smoking, total LAEF (61.16 ± 14.04 vs. 56.05 ± 12.72, p = 0.013) and active LAEF (43.98 ± 14.33 vs. 38.72 ± 13.51, p = 0.017) were lower, while passive LAEF (33.22 ± 14.11 vs. 31.28 ± 15.01, p = 0.807) remained unchanged in the DM + HP group compared to the DM-HP group. The DM + HP group had decreased εs (41.27 ± 18.89 vs. 33.41 ± 13.94, p = 0.006), εe (23.69 ± 12.96 vs. 18.90 ± 9.90, p = 0.037), εa (17.83 ± 8.09 vs. 14.93 ± 6.63, p = 0.019), and increased LACI (17.40±10.28 vs. 22.72±15.01, p = 0.049) when compared to the DM-HP group. In patients with DM, multivariate analysis revealed significant independent associations between LV GLS and εs (ß=-1.286, p < 0.001), εe (ß=-0.919, p < 0.001), and εa (ß=-0.324, p = 0.036). However, there was no significant association observed between LV GLS and LACI (ß=-0.003, p = 0.075). Additionally, hypertension was found to independently contribute to decreased εa (ß=-2.508, p = 0.027) and increased LACI in individuals with DM (ß = 0.05, p = 0.011). CONCLUSIONS: In DM patients, LV GLS showed a significant association with LA phasic strain. Hypertension was found to exacerbate the decline in LA booster strain and increase LACI in DM patients, indicating potential atrioventricular coupling index alterations.

Experts consensus on the procedure of dental operative microscope in endodontics and operative dentistry.

The dental operative microscope has been widely employed in the field of dentistry, particularly in endodontics and operative dentistry, resulting in significant advancements in the effectiveness of root canal therapy, endodontic surgery, and dental restoration. However, the improper use of this microscope continues to be common in clinical settings, primarily due to operators' insufficient understanding and proficiency in both the features and established operating procedures of this equipment. In October 2019, Professor Jingping Liang, Vice Chairman of the Society of Cariology and Endodontology, Chinese Stomatological Association, organized a consensus meeting with Chinese experts in endodontics and operative dentistry. The objective of this meeting was to establish a standard operation procedure for the dental operative microscope. Subsequently, a consensus was reached and officially issued. Over the span of about four years, the content of this consensus has been further developed and improved through practical experience.

Bushen Tongluo formula ameliorated testosterone propionate-induced benign prostatic hyperplasia in rats.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common disease in older men worldwide. However, there is currently no effective treatment for BPH. Bushen Tongluo Formula (Kidney-supplementing and collaterals-unblocking formula [KCF]) is a traditional Chinese medicine formula commonly used to ameliorate the symptoms of BPH, although the specific molecular mechanisms remain unclear. PURPOSE: We aimed to discover the effects and potential mechanisms of KCF against BPH. METHODS: Sixty male SD rats were randomly assigned to one of six group (n = 10): control, low-dosage KCF, medium-dosage KCF, high-dosage KCF, BPH model, and finasteride. A rat model of BPH was established by surgical castration followed by subcutaneous injection of testosterone propionate (TP) for 4 weeks. After treatment, the prostate index, histopathological staining, serum levels of estradiol (E2) and dihydrotestosterone (DHT), protein/mRNA levels of E-cadherin, TGF-ß1, caspase-3, Ki67, and vimentin, abundances of serum metabolites, and the proliferation, cell cycle, and apoptosis of BPH-1 cells were documented. RESULTS: KCF treatment for 4 weeks reduced the prostate volume and prostate index, alleviated histopathological changes to the prostate of rats with TP-induced BPH, decreased serum levels of E2 and DHT, reduced protein/mRNA levels of TGF-ß1 and vimentin, and increased E-cadherin levels. Moreover, KCF-spiked serum inhibited proliferation of BPH-1 cells, blocked the cell cycle, and promoted apoptosis. KCF was also found to regulate the contents of three metabolites (D-maltose, citric acid, and fumaric acid). CONCLUSION: The present study was the first to report that KCF exhibited therapeutic effects against BPH by regulating energy metabolism and inhibiting epithelial-mesenchymal transition in prostate tissues. Hence, KCF presents a viable treatment option for BPH.

Nomogram Models for Distinguishing Intraductal Carcinoma of the Prostate From Prostatic Acinar Adenocarcinoma Based on Multiparametric Magnetic Resonance Imaging.

OBJECTIVE: To compare multiparametric magnetic resonance imaging (MRI) features of intraductal carcinoma of the prostate (IDC-P) with those of prostatic acinar adenocarcinoma (PAC) and develop prediction models to distinguish IDC-P from PAC and IDC-P with a high proportion (IDC ≥ 10%, hpIDC-P) from IDC-P with a low proportion (IDC < 10%, lpIDC-P) and PAC. MATERIALS AND METHODS: One hundred and six patients with hpIDC-P, 105 with lpIDC-P and 168 with PAC, who underwent pretreatment multiparametric MRI between January 2015 and December 2020 were included in this study. Imaging parameters, including invasiveness and metastasis, were evaluated and compared between the PAC and IDC-P groups as well as between the hpIDC-P and lpIDC-P subgroups. Nomograms for distinguishing IDC-P from PAC, and hpIDC-P from lpIDC-P and PAC, were made using multivariable logistic regression analysis. The discrimination performance of the models was assessed using the receiver operating characteristic area under the curve (ROC-AUC) in the sample, where the models were derived from without an independent validation sample. RESULTS: The tumor diameter was larger and invasive and metastatic features were more common in the IDC-P than in the PAC group (P < 0.001). The distribution of extraprostatic extension (EPE) and pelvic lymphadenopathy was even greater, and the apparent diffusion coefficient (ADC) ratio was lower in the hpIDC-P than in the lpIDC-P group (P < 0.05). The ROC-AUCs of the stepwise models based solely on imaging features for distinguishing IDC-P from PAC and hpIDC-P from lpIDC-P and PAC were 0.797 (95% confidence interval, 0.750-0.843) and 0.777 (0.727-0.827), respectively. CONCLUSION: IDC-P was more likely to be larger, more invasive, and more metastatic, with obviously restricted diffusion. EPE, pelvic lymphadenopathy, and a lower ADC ratio were more likely to occur in hpIDC-P, and were also the most useful variables in both nomograms for predicting IDC-P and hpIDC-P.

Primary prostate Burkitt's lymphoma resected with holmium laser enucleation of the prostate: A rare case report.

BACKGROUND: Primary prostate Burkitt's lymphoma is a rare and aggressive condition with a poor prognosis. Its clinical presentation can be challenging to differentiate from benign prostatic hyperplasia. Given the rarity of primary prostate Burkitt's lymphoma, its diagnosis and treatment remain unclear. CASE SUMMARY: This report presents a case of a 57-year-old male with primary prostate Burkitt's lymphoma, initially misdiagnosed as prostatic hyperplasia. This case's operative process, intraoperative findings and postoperative management are discussed in detail. CONCLUSION: Primary prostate lymphoma is difficult to distinguish from other prostate diseases. Holmium laser enucleation of the prostate (HoLEP), a minimally invasive procedure, is crucial in diagnosing and treating this rare disease. Clinicians should remain vigilant and thoroughly combine physical examination, imaging and test results when encountering patients of younger age with small prostate size but a rapid progression of lower urinary tract symptoms. HoLEP is an essential diagnostic and therapeutic tool in managing primary prostate Burkitt's lymphoma.

Activation of Wnt/ß­Catenin­p130/E2F4 promotes the differentiation of bone marrow­derived mesenchymal stem cells into type II alveolar epithelial cells through cell cycle arrest.

The results of our previous study demonstrated that activation of the Wnt/ß-catenin pathway increased the differentiation of mesenchymal stem cells (MSCs) into type II alveolar epithelial (AT II) cells; however, the specific mechanisms remain unclear. The present study aimed to evaluate the role of Wnt/ß-catenin-p130/E2F transcription factor 4 (E2F4) in regulating the differentiation of mouse MSCs (mMSCs) into AT II cells, and to determine the specific mechanisms. mMSCs with p130 or E2F4 overexpression were constructed using lentiviral vectors. Differentiation of mMSCs into AT II cells was promoted using a modified coculture system with murine lung epithelial-12 cells incubated in small airway growth medium for 7-14 days. The differentiation efficiency was detected using immunofluorescence, western blot analysis and transmission electron microscopy. To detect the association between the canonical Wnt pathway and p130/E2F4, 4 mmol/l lithium chloride (LiCl) or 200 ng/ml Dickkopf-related protein 1 (DKK-1) was also added to the coculture system. Following differentiation, the cell cycle of mMSCs was evaluated using flow cytometry. The results of the present study demonstrated that surfactant protein C (SP-C) protein expression was higher in the p130 overexpression (MSC-p130) and E2F4 overexpression (MSC-E2F4) groups compared with the normal control mMSCs group following differentiation into AT II cells. Similar results for SP-C protein expression and lamellar body-like structures were also observed using immunofluorescence analysis and electron microscopy. Following the addition of LiCl into the coculture system for activation of the Wnt/ß-catenin signaling pathway, phosphorylated (p)-p130/p130 was slightly decreased at 7 days and E2F4 was increased both at 7 and 14 days in mMSCs. Furthermore, the p-p130/p130 ratio was significantly increased at 14 days and E2F4 was decreased both at 7 and 14 days following DKK-1-mediated inhibition of the Wnt pathway. The results of the present study demonstrated that the numbers of cells in G1 and S phases were increased following activation of the Wnt pathway and decreased following Wnt pathway inhibition. However, the number of cells in G1 phase was increased following the differentiation of mMSCs overexpressing p130 or E2F4. Therefore, the results of the present study revealed that the canonical Wnt signaling pathway may affect the differentiation of MSCs into AT II cells via regulation of downstream p130/E2F4. The specific mechanisms may be associated with G1 phase extension in the cell cycle of MSCs.

Predicting coronary atherosclerosis heart disease with pericoronary adipose tissue attenuation parameters based on dual-layer spectral detector computed tomography: a preliminary exploration.

Background: Coronary atherosclerosis is a chronic inflammatory condition. Pericoronary adipose tissue (PCAT) attenuation is closely related to coronary inflammation. This study aimed to investigate the relationship between PCAT attenuation parameters and coronary atherosclerotic heart disease (CAD) using dual-layer spectral detector computed tomography (SDCT). Methods: This cross-sectional study included eligible patients who underwent coronary computed tomography angiography using SDCT at the First Affiliated Hospital of Harbin Medical University between April 2021 and September 2021. Patients were classified as CAD (with coronary artery atherosclerotic plaque) or non-CAD (without coronary artery atherosclerotic plaque). Propensity score matching was used to match the two groups. The fat attenuation index (FAI) was used to quantify PCAT attenuation. The FAI was measured on conventional images (120 kVp) and virtual monoenergetic images (VMI) by semiautomatic software. The slope of the spectral attenuation curve (λ) was calculated. Regression models were established to evaluate the predictive value of PCAT attenuation parameters for CAD. Results: A total of 45 patients with CAD and 45 patients without CAD were enrolled. The PCAT attenuation parameters in the CAD group were significantly higher than those in the non-CAD group (all P values <0.05). The PCAT attenuation parameters of vessels with or without plaques in the CAD group were higher than those of vessels without plaques in the non-CAD group (all P values <0.05). In the CAD group, the PCAT attenuation parameters of vessels with plaques were slightly higher than those of vessels without plaques (all P values >0.05). In receiver operating characteristic curve analysis, the FAIVMI model achieved an area under the curve (AUC) of 0.8123 for discriminating between patients with and without CAD, which was higher than those of the FAI120 kVp model (AUC =0.7444) and the λ model (AUC =0.7230). However, the combined model of FAIVMI, FAI120 kVp, and λ obtained the best performance (AUC =0.8296) of all the models. Conclusions: PCAT attenuation parameters obtained using dual-layer SDCT can aid in distinguishing patients with and without CAD. By detecting increases in PCAT attenuation parameters, it might be possible to predict the formation of atherosclerotic plaques before they appear.

Pathological evaluation of renal complications in children following allogeneic hematopoietic stem cell transplantation: a retrospective cohort study.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for hematologic malignancies and non-malignant disorders, such as aplastic anemia, fanconi anemia, and certain immune deficiencies. Post-transplantation kidney injury is a common complication and involves a wide spectrum of structural abnormalities, including glomerular (MSPGN, mesangial proliferative glomerulonephritis; FSGS, focal segmental glomerulosclerosis; MPGN, membranoproliferative glomerulonephritis; MCD, minimal change disease), vascular (TMA, thrombotic microangiopathy), and/or tubulointerstitial (TIN, tubulointerstitial nephritis; ATI, acute tubular injury). Renal biopsy is the gold-standard examination for defining multiple etiologies of kidney impairment. Although kidney injury following HSCT has been studied, little is known about the effects of allo-HSCT on renal pathology in pediatric patients. METHODS: We retrospectively analyzed renal biopsy specimens from children with kidney injury after allo-HSCT and correlated results with clinical data in the last 10 years. RESULTS: Among 25 children (18 males and 7 females), three patients had proteinuria indicating nephrotic syndrome (24-hour urinary total protein/weight > 50 mg/kg/d), nine patients had severely reduced estimated glomerular filtration rate (eGFR < 30 ml/min/1.73 m2) and four patients received kidney replacement therapy (KRT). The main pathologies identified from kidney biopsies were MSPGN (n = 12), FSGS (n = 12), MPGN (n = 5), TMA (n = 4), MCD (n = 3), diffuse glomerular fibrosis (DGF, n = 2), ATI and TIN, in isolation or combined with other pathologies. The median follow-up time was 16.5 (0.5 ~ 68.0) months. Three patients died of recurrent malignancy and/or severe infection, one child developed to end-stage renal disease (ESRD), six patients (24%) had elevated serum creatinine (SCr > 100µmol/l) and nine patients (36%) still had proteinuria. CONCLUSIONS: This study evaluates histomorphologic findings from kidney biopsies of pediatric recipients following allo-HSCT. Detailed evaluation of renal biopsy samples is helpful to elucidate the nature of renal insult, and may potentially identify treatable disease processes.