Native T1 mapping-based radiomics diagnosis of kidney function and renal fibrosis in chronic kidney disease.

Chronic kidney disease (CKD) raises major concerns for global public health as it is characterized by high prevalence, low awareness, high healthcare costs, and poor prognosis. Therefore, our study prospectively established and validated native T1 mapping-based radiomics models for the prediction of renal fibrosis and renal function in patients with CKD. Moreover, the area under the receiver operating characteristic curve (AUC) and diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were used to evaluate its performance. Thus, our results show that radiomics based on native T1 mapping images can better identify renal function and renal fibrosis in patients with CKD and outperform conventional T1 mapping parameters of ΔT1 and T1%, thus providing more information for CKD management and clinical decision-making.

Melatonin derivative 6a protects Caenorhabditis elegans from formaldehyde neurotoxicity via ADH5.

Formaldehyde (FA) is a carcinogen that is not only widespread in the environment, but is also produced endogenously by metabolic processes. In organisms, FA is converted to formic acid in a glutathione (GSH)-dependent manner by alcohol dehydrogenase 5 (ADH5). The abnormal accumulation of FA in the body can cause a variety of diseases, especially cognitive impairment leading to Alzheimer's disease (AD). In this study, melatonin derivative 6a (MD6a) markedly improved the survival and chemotactic performance of wild-type Caenorhabditis elegans exposed to high concentrations of FA. MD6a lowered FA levels in the nematodes by enhancing the release of covalently-bound GSH from S-hydroxymethyl-GSH in an adh-5-dependent manner. In addition, MD6a protected against mitochondrial dysfunction and cognitive impairment in beta-amyloid protein (Aß) transgenic nematodes by lowering endogenous FA levels and reducing Aß aggregation in an adh-5-dependent manner. Our findings suggest that MD6a detoxifies FA via ADH5 and protects against Aß toxicity by reducing endogenous FA levels in the C. elegans AD models. Thus, ADH5 might be a potential therapeutic target for FA toxicity and AD.

Identification of mutations in viral proteins involved in cell adaptation using a reverse genetic system of the live attenuated hepatitis A virus vaccine H2 strain.

The live attenuated hepatitis A virus vaccine H2 strain was developed by passaging a wild- type H2w isolate in cell cultures. Currently, the mechanism underlying its attenuation phenotype remain largely unknown. In this study, we generated a full-length infectious cDNA clone of the H2 strain using in-fusion techniques. The recovered H2 strain (H2ic) from the cDNA clone exhibited an efficient replication in both the hepatoma cell line Huh7.5.1 and the 2BS cell line used for vaccine production, similar to the parental H2 strain. Additionally, H2ic did not cause disease in Ifnar1-/- C57 mice, consistent with the H2 strain. To explore the cell-adaptive mutations of the H2 strain, chimeric viruses were generated by replacing its non-structural proteins with corresponding regions from H2w using the infectious cDNA clone as a genetic backbone. The chimeric viruses carrying the 3C or 3D proteins from H2w showed decreased replication in Huh7.5.1 and 2BS cell lines compared to H2ic. Other chimeric viruses containing the 2B, 2C, or 3A proteins from H2w failed to be recovered. Furthermore, there were no significant differences in disease manifestation in mice between H2ic and the recovered chimeric viruses. These results demonstrate that adaptive mutations in the 2B, 2C, and 3A proteins are essential for efficient replication of the H2 strain in cell cultures. Mutations in the 3C and 3D proteins contribute to enhanced replication in cell cultures but did not influence the attenuated phenotypes in mice. Together, this study presents the first reverse genetic system of the H2 strain and identifies viral proteins essential for adaptation to cell cultures.

Antisense Oligonucleotide Therapy for Calmodulinopathy.

BACKGROUND: Calmodulinopathies are rare inherited arrhythmia syndromes caused by dominant heterozygous variants in CALM1, CALM2, or CALM3, which each encode the identical CaM (calmodulin) protein. We hypothesized that antisense oligonucleotide (ASO)-mediated depletion of an affected calmodulin gene would ameliorate disease manifestations, whereas the other 2 calmodulin genes would preserve CaM level and function. METHODS: We tested this hypothesis using human induced pluripotent stem cell-derived cardiomyocyte and mouse models of CALM1 pathogenic variants. RESULTS: Human CALM1F142L/+ induced pluripotent stem cell-derived cardiomyocytes exhibited prolonged action potentials, modeling congenital long QT syndrome. CALM1 knockout or CALM1-depleting ASOs did not alter CaM protein level and normalized repolarization duration of CALM1F142L/+ induced pluripotent stem cell-derived cardiomyocytes. Similarly, an ASO targeting murine Calm1 depleted Calm1 transcript without affecting CaM protein level. This ASO alleviated drug-induced bidirectional ventricular tachycardia in CalmN98S/+ mice without a deleterious effect on cardiac electrical or contractile function. CONCLUSIONS: These results provide proof of concept that ASOs targeting individual calmodulin genes are potentially effective and safe therapies for calmodulinopathies.

Overexpression of ZlMYB1 and ZlMYB2 increases flavonoid contents and antioxidant capacity and enhances the inhibition of α-glucosidase and tyrosinase activity in rice seeds.

Anthocyanins are natural flavonoids with a high antioxidant power and many associated health benefits, but most rice produce little amounts of these compounds. In this study, 141 MYB transcription factors in 15 chromosomes, including the nucleus-localised ZlMYB1 (Zla03G003370) and ZlMYB2 (Zla15G015220), were discovered in Zizania latifolia. Overexpression of ZlMYB1 or ZlMYB2 in rice seeds induced black pericarps, and flavonoid content, antioxidant capacity, and α-glucosidase and tyrosinase inhibition effects significantly increased compared to those in the control seeds. ZlMYB1 and ZlMYB2 overexpression induced the upregulation of 764 and 279 genes, respectively, and the upregulation of 162 and 157 flavonoids, respectively, linked to a black pericarp phenotype. The expression of flavonoid 3'-hydroxylase and UDP-glycose flavonoid glycosyltransferase, as well as the activities of these enzymes, increased significantly in response to ZlMYB1 or ZlMYB2 overexpression. This study systematically confirmed that the overexpression of ZlMYB1 and ZlMYB2 promotes flavonoid biosynthesis (especially of anthocyanins) in rice.

Bioinspired Zwitterionic Block Polymer-Armored Nitric Oxide-Generating Coating Combats Thrombosis and Biofouling.

Thrombosis and infection are 2 major complications associated with central venous catheters (CVCs), resulting in substantial mortality and morbidity. The concurrent long-term administration of antibiotics and anticoagulants to address these complications have been demonstrated to cause severe side effects such as antibiotic resistance and bleeding. To mitigate these complications with minimal or no drug utilization, we developed a bioinspired zwitterionic block polymer-armored nitric oxide (NO)-generating functional coating for surface modification of CVCs. This armor was fabricated by precoating with a Cu-dopamine (DA)/selenocysteamine (SeCA) (Cu-DA/SeCA) network film capable of catalytically generating NO on the CVCs surface, followed by grafting of a zwitterionic p(DMA-b-MPC-b-DMA) polymer brush. The synergistic effects of active attack by NO and copper ions provided by Cu-DA/SeCA network and passive defense by zwitterionic polymer brush imparted the CVCs surface with durable antimicrobial properties and marked inhibition of platelets and fibrinogen. The in vivo studies confirmed that the surface-armored CVCs could effectively reduce inflammation and inhibit thrombosis, indicating a promising potential for clinical applications.

Comparison of Infection Risks Between Various Inhaled and Intranasal Corticosteroids: A Pharmacovigilance Analysis Based on the FAERS Database.

Purpose: This study conducted a pharmacovigilance analysis based on the FDA Adverse Event Reporting System (FAERS) database to compare the infection risk of inhaled or nasal Beclomethasone, Fluticasone, Budesonide, Ciclesonide, Mometasone, and Triamcinolone Acetonide. Methods: We used proportional imbalance analysis to evaluate the correlation between ICS /INCs and infection events. The data was extracted from the FAERS database from April 2015 to September 2023. Further analysis was conducted on the clinical characteristics, site of infection, and pathogenic bacteria of ICS and INCs infection adverse events (AEs). We used bubble charts to display their top 5 infection adverse events. Results: We analyzed 21,837 reports of infection AEs related to ICS and INCs, with an average age of 62.12 years. Among them, 61.14% of infection reports were related to females. One-third of infections reported to occur in the lower respiratory tract with Fluticasone, Budesonide, Ciclesonidec, and Mometasone; over 40% of infections reported by Triamcinolone Acetonide were eye infections; the rate of oral infections caused by Beclomethasone were 7.39%. The reported rates of fungal and viral infections caused by beclomethasone were 21.15% and 19.2%, respectively. The mycobacterial infections caused by Budesonide and Ciclesonidec account for 3.29% and 2.03%, respectively. Bubble plots showed that the ICS group had more fungal infections, oral infections, pneumonia, tracheitis, etc. The INCs group had more eye symptoms, rhinitis, sinusitis, nasopharyngitis, etc. Conclusion: Women who use ICS and INCs are more prone to infection events. Compared to Budesonide, Fluticasone seemed to have a higher risk of pneumonia and oral candidiasis. Mometasone might lead to more upper respiratory tract infections. The risk of oral infection was higher with Beclomethasone. Beclomethasone causes more fungal and viral infections, while Ciclesonide and Budesonide are more susceptible to mycobacterial infections.

Artesunate inhibits vasculogenic mimicry in choroidal melanoma through HIF-1 α/ VEGF/PDGF pathway.

Choroidal melanoma (CM), a highly metastatic eye tumor, exhibits vasculogenic mimicry (VM) facilitated by hypoxia-induced angiogenesis. This study explored the inhibitory impact of the anti-malarial drug Artesunate (ART) on CM VM through modulation of the HIF-1α/VEGF/PDGF pathway. Immunohistochemistry (IHC) confirmed VM in CM with elevated VEGF and PDGF expression. Hypoxia promoted CM proliferation, upregulating HIF-1α, VEGF and PDGF. VEGF and PDGF enhanced CM migration, invasion and VM, with HIF-1α playing a crucial role. ART mitigated VM formation by suppressing the HIF-1α/VEGF/PDGF pathway, highlighting its potential as an anti-tumor agent in CM.

The molecular genetics of PI3K/PTEN/AKT/mTOR pathway in the malformations of cortical development.

Malformations of cortical development (MCD) are a group of developmental disorders characterized by abnormal cortical structures caused by genetic or harmful environmental factors. Many kinds of MCD are caused by genetic variation. MCD is the common cause of intellectual disability and intractable epilepsy. With rapid advances in imaging and sequencing technologies, the diagnostic rate of MCD has been increasing, and many potential genes causing MCD have been successively identified. However, the high genetic heterogeneity of MCD makes it challenging to understand the molecular pathogenesis of MCD and to identify effective targeted drugs. Thus, in this review, we outline important events of cortical development. Then we illustrate the progress of molecular genetic studies about MCD focusing on the PI3K/PTEN/AKT/mTOR pathway. Finally, we briefly discuss the diagnostic methods, disease models, and therapeutic strategies for MCD. The information will facilitate further research on MCD. Understanding the role of the PI3K/PTEN/AKT/mTOR pathway in MCD could lead to a novel strategy for treating MCD-related diseases.

[Study on optimal harvesting period and rational medicinal parts of Zanthoxylum nitidum based on statistics of main effective components].

To determine the optimal harvesting period and rational medicinal parts of Zanthoxylum nitidum, the main effective components of cultivated Z. nitidum samples, which originate from various growth years, harvesting months, and different parts were analyzed and compared with the wild samples. HPLC was performed on a Kinetex C18 column(4. 6 mm×100 mm, 2. 6 µm) with the gradient elution of 0. 3% phosphoric acid solution-acetonitrile(80 ∶ 20) containing 0. 2% triethylamine. The flow rate was 1. 0 m L·min-1, and the detection wavelength was 273 nm. The column temperature was 30 ℃. Nitidine chloride and chelerythrine, the main effective components, were determined as the markers. The results showed there was no significant difference in the contents of the main effective components among the roots of wild and cultivated Z. nitidum, as well as the roots and roots + stems of cultivated Z. nitidum. The statistical results of HCA and PCA indicated that the roots and stems could be clearly distinguished, but no distinction could be made between wild and cultivated products, which was consistent with the results of the significance analysis. The total contents of nitidine chloride and chelerythrine in roots and stems of Z. nitidum of 1-6 years old were 0. 114%-0. 256% and 0. 030%-0. 133%, respectively. These results suggested a positive correlation between the content of the main effective components and the growth years. No significant difference was observed between the contents of samples harvested in different seasons, indicating that the harvest season had no effect on the content of the main effective components of the Z. nitidum samples. The total contents of nitidine chloride and chelerythrine of the dried Z. nitidum samples(excluding branches) from three plantation bases were 0. 308%±0. 123% in Yunfu, 0. 192%±0. 025% in Maoming, and 0. 197%±0. 052% in Nanning, respectively, and they were all not less than 0. 15%, or in other words, the roots(including fibrous roots, taproots, and underground stems) and stems(aboveground stems) of Z. nitidum transplanted for more than 2. 5 years can meet the medical requirements. This study demonstrates that the cultivated Z. nitidum could be used as a valid substitute for the wild Z. nitidum, which provides a guarantee for the sustainable development and the application of Z. nitidum resources. The stems and roots could be considered medicinal parts of Z. nitidum. It is recommended to revise the medicinal parts of Z. nitidum to dried roots and stems in the next edition of Chinese Pharmacopoeia, and the medicinal parts can be harvested all year round. In order to ensure the content of effective components and clinical effectiveness, the root and stem should be harvested for medical use after the seedlings of Z. nitidum have been transplanted for more than three years.

An integrated network pharmacology approach reveals that Ampelopsis grossedentata improves alcoholic liver disease via TLR4/NF-κB/MLKL pathway.

BACKGROUND: Alcohol-related liver damage is the most prevalent chronic liver disease, which creates a heavy public health burden worldwide. The leaves of Ampelopsis grossedentata have been considered a popular tea and traditional herbal medicine in China for more than one thousand years, and possess anti-inflammatory, antioxidative, hepatoprotective, and antiviral activities. PURPOSE: We explored the protective effects of Ampelopsis grossedentata extract (AGE) against chronic alcohol-induced hepatic injury (alcoholic liver disease, ALD), aiming to elucidate its underlying mechanisms. METHODS: Firstly, UPLC-Q/TOF-MS analysis and network pharmacology were used to identify the constituents and elucidate the potential mechanisms of AGE against ALD. Secondly, C57BL/6 mice were pair-fed the Lieber-DeCarli diet containing either isocaloric maltodextrin or ethanol, AGE (150 and 300 mg/kg/d) and silymarin (200 mg/kg) were administered to chronic ethanol-fed mice for 7 weeks to evaluate the hepatoprotective effects. Serum biochemical parameters were determined, hepatic and ileum sections were used for histologic examination, and levels of inflammatory cytokines and oxidative stress in the liver were examined. The potential molecular mechanisms of AGE in improving ALD were demonstrated by RNA-seq, Western blotting analysis, and immunofluorescence staining. RESULTS: Ten main constituents of AGE were identified using UPLC-Q/TOF-MS and 274 potential ALD-related targets were identified. The enriched KEGG pathways included Toll-like receptor signaling pathway, NF-κB signaling pathway, and necroptosis. Moreover, in vivo experimental studies demonstrated that AGE significantly reduced serum aminotransferase levels and improved pathological abnormalities after chronic ethanol intake. Meanwhile, AGE improved ALD in mice by down-regulating oxidative stress and inflammatory cytokines. Furthermore, AGE notably repaired damaged intestinal epithelial barrier and suppressed the production of gut-derived lipopolysaccharide by elevating intestinal tight junction protein expression. Subsequent RNA-seq and experimental validation indicated that AGE inhibited NF-κB nuclear translocation, suppressed IκB-α, RIPK3 and MLKL phosphorylation and alleviated hepatic necroptosis in mice. CONCLUSION: In this study, we have demonstrated for the first time that AGE protects against alcoholic liver disease by regulating the gut-liver axis and inhibiting the TLR4/NF-κB/MLKL-mediated necroptosis pathway. Therefore, our present work provides important experimental evidence for AGE as a promising candidate for protection against ALD.

Hu8F4-CAR T cells with mutated Fc spacer segment improve target specificity and mediate anti-leukemia activity in vivo.

BACKGROUND AIMS: Hu8F4 is a T-cell receptor-like antibody with high affinity for the leukemia-associated antigen PR1/HLA-A2 epitope. Adapted into a chimeric antigen receptor (CAR) format, Hu8F4-CAR is composed of the Hu8F4 single-chain variable fragment, the human IgG1 CH2CH3 extracellular spacer domain, a human CD28 costimulatory domain and the human CD3ζ signaling domain. We have demonstrated high efficacy of Hu8F4-CAR-T cells against PR1/HLA-A2-expressing cell lines and leukemic blasts from patients with acute myeloid leukemia in vitro. Previous studies have shown that modification of the Fc domains of IgG4 CH2CH3 spacer regions can eliminate activation-induced cell death and off-target killing mediated by mouse Fc gamma receptor-expressing cells. METHODS: We generated Hu8F4-CAR(PQ) with mutated Fc receptor binding sites on the CH2 domain of Hu8F4-CAR to prevent unwanted interactions with Fc gamma receptor-expressing cells in vivo. RESULTS: The primary human T cells transduced with Hu8F4-CAR(PQ) can specifically lyse HLA-A2+ PR1-expressing leukemia cell lines in vitro. Furthermore, both adult donor-derived and cord blood-derived Hu8F4-CAR(PQ)-T cells are active and can eliminate U937 leukemia cells in NSG mice. CONCLUSIONS: Herein, we demonstrate that modification of the IgG1-based spacer can eliminate Fc receptor binding-induced adverse effects and Hu8F4-CAR(PQ)-T cells can kill leukemia in vivo.

Proximal Femoral Metastasis From Epidermal Growth Factor Receptor-Mutated Lung Adenocarcinoma Mimicking Osteosarcoma on Magnetic Resonance Imaging.

The aggressive nature of lung cancer is frequently accompanied by a high incidence of bone metastasis; however, proximal femoral metastasis from lung cancer is comparatively uncommon when compared to other malignancies. In this report, we present the case of a 53-year-old Asian male who presented with pain in the left thigh and back. Magnetic resonance imaging revealed severe bone destruction with involvement of adjacent soft tissue mass at the left thigh, exhibiting imaging findings that mimic osteosarcoma. Subsequent bone biopsy confirmed the diagnosis of epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma with bone metastasis. The patient achieved survival following administration of osimertinib and underwent surgery for femoral metastases without palliative surgery for lung cancer. Therefore, proximal femoral metastasis from EGFR-mutated lung adenocarcinoma should be considered as a differential diagnosis in patients suspected to have osteosarcoma. The imaging findings of proximal femoral metastasis from EGFR-mutated lung adenocarcinoma were presented, and their therapeutic management was discussed.

Are older adults less generous? Age differences in emotion-related social decision making.

In social interaction, age-related differences in emotional processing may lead to varied social decision making between young and older adults. However, previous studies of social decision making have paid less attention to the interactants' emotions, leaving age differences and underlying neural mechanisms unexplored. To address this gap, the present study combined functional and structural magnetic resonance imaging, employing a modified dictator game task with recipients displaying either neutral or sad facial expressions. Behavioral results indicated that although older adults' overall allocations did not differ significantly from those of young adults, older adults' allocations showing a decrease in emotion-related generosity compared to young adults. Using representational similarity analysis, we found that older adults showed reduced neural representations of recipients' emotions and gray matter volume in the right anterior cingulate gyrus (ACC), right insula, and left dorsomedial prefrontal cortex (DMPFC) compared to young adults. More importantly, mediation analyses indicated that age influenced allocations not only through serial mediation of neural representations of the right insula and left DMPFC, but also through serial mediation of the mean gray matter volume of the right ACC and left DMPFC. This study identifies the potential neural pathways through which age affects emotion-related social decision making, advancing our understanding of older adults' social interaction behavior that they may not be less generous unless confronted with individuals with specific emotions.

In vivo proximity proteomics uncovers palmdelphin (PALMD) as a Z-disc-associated mitigator of isoproterenol-induced cardiac injury.

Z-discs are core ultrastructural organizers of cardiomyocytes that modulate many facets of cardiac pathogenesis. Yet a comprehensive proteomic atlas of Z-disc-associated components remain incomplete. Here, we established an adeno-associated virus (AAV)-delivered, cardiomyocyte-specific, proximity-labeling approach to characterize the Z-disc proteome in vivo. We found palmdelphin (PALMD) as a novel Z-disc-associated protein in both adult murine cardiomyocytes and human pluripotent stem cell-derived cardiomyocytes. Germline and cardiomyocyte-specific Palmd knockout mice were grossly normal at baseline but exhibited compromised cardiac hypertrophy and aggravated cardiac injury upon long-term isoproterenol treatment. By contrast, cardiomyocyte-specific PALMD overexpression was sufficient to mitigate isoproterenol-induced cardiac injury. PALMD ablation perturbed the transverse tubule (T-tubule)-sarcoplasmic reticulum (SR) ultrastructures, which formed the Z-disc-associated junctional membrane complex (JMC) essential for calcium handling and cardiac function. These phenotypes were associated with the reduction of nexilin (NEXN), a crucial Z-disc-associated protein that is essential for both Z-disc and JMC structures and functions. PALMD interacted with NEXN and enhanced its protein stability while the Nexn mRNA level was not affected. AAV-based NEXN addback rescued the exacerbated cardiac injury in isoproterenol-treated PALMD-depleted mice. Together, this study discovered PALMD as a potential target for myocardial protection and highlighted in vivo proximity proteomics as a powerful approach to nominate novel players regulating cardiac pathogenesis.

Rare primary squamous cell carcinoma of the intrahepatic bile duct: A case report and review of literature.

BACKGROUND: Cholangiocarcinoma is the most common malignancy of the biliary tree and has a poor prognosis. Adenocarcinoma is the most common pathological type of cholangiocarcinomas, but rare squamous, adenosquamous, and mucinous variants have been reported without adequate clinical data. CASE SUMMARY: This report describes a rare case of primary squamous cell carcinoma (SCC) of the intrahepatic bile duct. The patient was admitted with a tumor in the hepatic caudate lobe with no obvious clinical symptoms. Examination revealed hepatitis B surface antigen positivity, a slight increase in alfa-fetoprotein to 16.34 ng/mL, and an irregular slightly heterogeneous enhancing lesion in the hepatic caudate lobe, which was initially thought to be hepatocellular carcinoma. Laparoscopic resection was performed, and the final pathology suggested a rare primary SCC of the intrahepatic bile duct. Immunohistochemistry indicated positivity for villin, partial positivity for p63, and negativity for hepatocyte, CK7, CK8, CK19, and CK20. The Ki-67 index was approximately 60%. The patient received six cycles of Tegio chemotherapy. A new lesion was detected in the liver after 15 months. The surgery was performed, and the patient was followed-up at a local hospital. To date, no new lesions have been observed. CONCLUSION: Surgery is the first choice for resectable lesions, and combined chemotherapy based on pathology is essential for increasing overall survival.

The effect of ADAMTS13 on graft-versus-host disease.

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) can potentially cure malignant blood disorders and benign conditions such as haemoglobinopathies and immunologic diseases. However, allo-HSCT is associated with significant complications. The most common and debilitating among them is graft-versus-host disease (GVHD). In GVHD, donor-derived T cells mount an alloimmune response against the recipient. The alloimmune response involves several steps, including recognition of recipient antigens, activation and proliferation of T cells in secondary lymphoid organs, and homing into GVHD-targeted organs. Adhesion molecules on T cells and endothelial cells mediate homing of T cells into lymphoid and non-lymphoid tissues. In this study, we showed that Von Willebrand factor (VWF), an adhesion molecule secreted by activated endothelial cells, plays an important role in mouse models of GVHD. We investigated the effect of the VWF-cleaving protease ADAMTS13 on GVHD. We found that ADAMTS13 reduced the severity of GVHD after bone marrow transplantation from C57BL6 donor to BALB/C recipient mice. A recombinant VWF-A2 domain peptide also reduced GVHD in mice. We showed that ADAMTS13 and recombinant VWF-A2 reduced the binding of T cells to endothelial cells and VWF in vitro, and reduced the number of T cells in lymph nodes, Peyer's patches and GVHD-targeted organs in vivo. We identified LFA-1 (αLß2) as the binding site of VWF on T cells. Our results showed that blocking T-cell homing by ADAMTS13 or VWF-A2 peptide reduced the severity of the GVHD after allo-HSCT, a potentially novel method for treating and preventing GVHD.

Study on the expression patterns of inner root sheath-specific genes in Tan sheep hair follicle during different developmental stages.

By analyzing the expression patterns of inner root sheath (IRS) specific genes during different developmental stages of hair follicle (HF) in Tan sheep embryos and at birth, this study aims to reveal the influence of the IRS on crimped wool. Skin tissues from the scapular region of male Tan sheep were collected at 85 days (E85) and 120 days (E120) of fetal development, and at 0 days (D0), 35 days (D35), and 60 days (D60) after birth, with four samples at each stage. Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to determine the relative expression levels of IRS type I keratin genes (KRT25, KRT26, KRT27, KRT28), type II keratin genes (KRT71, KRT72, KRT73, KRT74), and the trichohyalin gene (TCHH) in the skin of Tan sheep at different stages. Results showed that the expression levels of all IRS-specific genes peaked at D0, with the expression of all genes significantly higher than at E85 (P < 0.01), except for KRT73 and TCHH. The expression levels of KRT25, KRT26, and KRT72 were also significantly higher than at E120 (P < 0.01). Furthermore, the expression levels of KRT27, KRT28, KRT71, and KRT74 were significantly higher than both at E120 and D35 (P < 0.01). The expression levels of other genes at different stages showed no significant difference (P > 0.05). Conclusion: The IRS-specific genes exhibit the highest expression levels in Tan sheep at the neonatal stage. The expression levels of KRT71, KRT72, and TCHH, which are consistent with the pattern of wool crimp, may influence the morphology of the IRS and thereby affect the crimp of Tan sheep wool.

[A nomogram for predicting residual back pain after percutaneous vertebroplasty for osteoporotic vertebral compression fractures].

OBJECTIVE: To construct percutaneous vertebroplasty for predicting osteoporotic vertebral compression fractures (OVCFs) nomogram of residual back pain (RBP) after percutaneous vertebroplasty(PVP). METHODS: Clinical data of 245 OVCFs patients who were performed PVP from January 2020 to December 2022 were retrospectively analyzed, including 47 males and 198 females, aged from 65 to 77 years old with an average of (71.47±9.03) years old, and were divided into RBP group and non-RBP group according to whether RBP occurred. Gender, age, comorbidities, fracture stage, body mass index (BMI), bone mineral density (BMD), visual analogue scale (VAS), Oswestry disability index (ODI) and other general information were collected; anterior vertebral height (AVH), anterior vertebral height ratio (AVH), anterior vertebral height ratio(AVHR), Cobb angle, intravertebral vacuum cleft (IVC), thoracolumbar fascia (TLF) injury, paravertebral muscle steatosis, injection volume and leakage of bone cement, bone cement dispersion pattern, anterior vertebral height recovery ratio (AVHRR), Cobb angle changes, etc. imaging parameters before operation and 24 h after operation were collected. Univariate analysis was performed to analysis above factors, and multivariate Logistic regression model was used to investigate independent risk factors for postoperative RBP, and Nomogram model was constructed and verified;receiver operating characteristic(ROC) curve and calibration curve were used to determine predictive performance and accuracy of the model, and Hosmer-Lemeshow (H-L) test was used for evaluation. The area under curve (AUC) of ROC was calculated, and Harrell consistency index (C index) was used to evaluate the predictive efficiency of model;decision curve analysis (DCA) was used to evaluate clinical practicability of model. RESULTS: There were 34 patients in RBP group and 211 patients in non-RBP group. There were no significant differences in gender, age, comorbidities, fracture stage, BMI, BMD, VAS, ODI, AVH, AVHR and Cobb angle between two groups (P>0.05). Univariate analysis showed 6 patients occurred IVC in RBP group and 13 patients in non-RBP, the number of IVC in RBP group was higher than that in non-RBP group (χ2=5.400, P=0.020);6 patients occuured TLF injury in RBP group and 11 patients in non-RBP group, the number of TLF injury in RBP group was higher than that in non-RBP group (χ2=7.011, P=0.008);In RBP group, 18 patients with grade 3 to 4 paraptebral steatosis and 41 patients in non-RBP group, RBP group was higher than non-RBP group (χ2=21.618, P<0.001), and the proportion of bone cement mass in RBP group was higher than non-RBP group (χ2=6.836, P=0.009). Multivariate Logistic regression analysis showed IVC (χ2=4.974, P=0.025), TLF injury (χ2=5.231, P=0.023), Goutallier grade of paravertebral steatosis >2 (χ2=15.124, P<0.001) and proportion of bone cement (χ2=4.168, P=0.038) were independent risk factors for RBP after PVP. ROC curve of model showed AUC of original model was 0.816[OR=2.862, 95%CI (0.776, 0.894), P<0.001]. The internal verification of model through 200 bootstrap samples showed the value of C index was 0.936, and calibration curve showed predicted probability curve was close to actual probability curve. H-L goodness of fit test results were χ2=5.796, P=0.670. DCA analysis results showed the decision curve was above None line and All line when the threshold value ranged from 6% to 71%. CONCLUSION: IVC, TLF combined injury, paravertebral muscle steatosis with Goutallier grade> 2, and bone cement diffusion with mass type are independent risk factors for RBP after PVP. The risk prediction model for RBP after PVP established has good predictive performance and good clinical practicability.

Effect of nutritional status on adverse clinical events in elderly patients with nonvalvular atrial fibrillation: A retrospective cohort study.

OBJECTIVE: To explore the influence of nutritional status on adverse clinical events in elderly patients with nonvalvular atrial fibrillation. METHODS: This retrospective observational cohort study included 196 patients, 75-102-years-old, with nonvalvular atrial fibrillation, hospitalized in our hospital. The nutritional status was assessed using Mini-Nutritional Assessment-Short Form (MNA-SF). Patients with MNA-SF scores of 0-11 and 12-14 were included in the malnutrition and nonmalnutrition groups, respectively. RESULTS: The average age of the malnutrition group was higher than that of the nonmalnutrition group, and the levels of body mass index (BMI), hemoglobin (HGB), and albumin (ALB) were significantly lower than those of the nonmalnutrition group, with statistical significance (p < .05). The incidence of all-cause death in the malnutrition group was higher than that in the nonmalnutrition group (p = .007). Kaplan-Meier curve indicated that malnutrition patients have a higher risk of all-cause death (log-rank test, p = .001) and major bleeding events (p = .017). Multivariate Cox proportional hazard regression analysis corrected for confounders showed that malnutrition was an independent risk factor of all-cause death (HR = 1.780, 95%CI:1.039-3.050, p = .036). The malnutrition group had a significantly high incidence of major bleeding than the nonmalnutrition group (p = .026), and there was no significant difference in the proportion of anticoagulation therapy (p = .082) and the incidence of ischemic stroke/systemic embolism (p = .310) between the two groups. CONCLUSIONS: Malnutrition is an independent risk factor of all-cause death in elderly patients with atrial fibrillation. The incidence of major bleeding in malnourished elderly patients with atrial fibrillation is high, and the benefit of anticoagulation therapy is not obvious.