Various clinical manifestations of 223 patients with IgE deficiency in a tertiary hospital in China: A cross-sectional study.

High Immunoglobulin E(IgE) levels associated with hypersensitivity or parasitic infection were well established, but the clinical significance of ultra-low IgE was largely unknown. Previous studies indicated these patients have an elevated risk of cancer, but large-scale epidemiological studies on the prevalence and clinical manifestations of these ultra-low IgE patients are still lacking. A total of 62,997 patients who were admitted to the First Affiliated Hospital of Wenzhou Medical University and had IgE level tests from January 2010 to March 2020 were included. Patients with serum IgE levels < 2 IU/mL were defined to have ultra-low IgE. And the clinical characteristics of these patients were retrospectively analyzed based on electronic medical record system and follow-up. A total of 223 patients (223/62,997, 0.35%) had ultra-low IgE were documented in 62,997 patients who had IgE tests. Among the clinical manifestations of these 223 ultra-low IgE patients, infection ranked first (125/223, 56.05%), following allergic diseases (51/223, 22.87%), hematological disorders (37/223, 16.59%), tumor (27/223, 12.11%) and autoimmune diseases (23/223, 10.31%). To the best of our knowledge, we first reported that the prevalence and clinical characteristics of 223 ultra-low IgE patients in China. The most common comorbidities were infection, allergic diseases, hematological disorders, tumor and autoimmune diseases.

CD8+ T cell-based cancer immunotherapy.

The immune system in humans is a defense department against both exogenous and endogenous hazards, where CD8+ T cells play a crucial role in opposing pathological threats. Various immunotherapies based on CD8+ T cells have emerged in recent decades, showing their promising results in treating intractable diseases. However, in the fight against the constantly changing and evolving cancers, the formation and function of CD8+ T cells can be challenged by tumors that might train a group of accomplices to resist the T cell killing. As cancer therapy stepped into the era of immunotherapy, understanding the physiological role of CD8+ T cells, studying the machinery of tumor immune escape, and thereby formulating different therapeutic strategies become the imperative missions for clinical and translational researchers to fulfill. After brief basics of CD8+ T cell-based biology is covered, this review delineates the mechanisms of tumor immune escape and discusses different cancer immunotherapy regimens with their own advantages and setbacks, embracing challenges and perspectives in near future.

Imaging Features and Misdiagnosis of Giant Cerebral Cavernous Malformations.

BACKGROUND: While cerebral cavernous malformations (CCMs) have been extensively described, few reports have described the imaging appearance of giant CCMs (GCCMs). OBJECTIVE: To describe the imaging characteristics of GCCMs and study the reasons for preoperative misdiagnosis. METHODS: We retrospectively analyzed the data of 12 patients (5 men, 7 women; mean age, 35.23 ± 12.64 years) with histopathologically confirmed GCCMs. Two radiologists analyzed the CT (n = 12) and MRI (n = 10) features: location, number, size, shape, boundary, signal intensity, and enhancement. RESULTS: The sellar region, cerebral hemisphere, skull bone, and ventricle were involved in 5, 4, 2, and 1 patients, respectively. Three tumors were irregularly shaped, while nine were oval. Eleven lesions showed slightly high- and/or high-density on CT; 1 lesion appeared as a low-density cyst. Calcifications were found in 11 lesions. Four tumors showed uniform hypointensity on T1-weighted imaging (T1WI) and hyperintense signals on T2-weighted imaging (T2WI). Six tumors showed mixed low-, equal-, and high-intensity signals on T1WI and T2WI. Noticeable contrast enhancement and gradual strengthening were noted on T1WI. Ten lesions showed hemorrhage and hemosiderin deposition. The GCCMs were wrongly diagnosed as cartilage-derived tumors/ meningioma (3 patients); tumor and hematoma (2 patients each); and pituitary tumor/ meningioma, chondroma, chordoma, ependymoma, and macroadenoma (1 patient each). CONCLUSIONS: GCCMs present as an oval mass with slightly high- and/or high-density calcifications on CT and show hemorrhage and hemosiderin accumulation on MRI. Therefore, slightly high- and/or high-density calcification and hemosiderin accumulation are critical clinical characteristics of GCCMs.

A novel link between melatonin and circ_0005753/PTBP1/TXNIP regulatory network in the modulation of osteogenic potential in mesenchymal stem cells.

Labeled with pluripotent potential, the transplantation of bone marrow mesenchymal stem cells (BMSCs) is considered as a promising strategy for treating osteoporosis (OP). Melatonin (MEL) has been investigated to be an essential regulator involved in bone metabolism, as well as BMSCs differentiation. Circular RNAs (circRNAs) are a unique kind of non-coding RNA and play an important regulatory role in OP. However, whether circRNAs are implicated in the effects of MEL on BMSCs osteogenic differentiation remains largely indeterminate. Expression of circ_0005753 in human BMSCs with MEL treatment, clinical specimens diagnosed with OP, either with ovariectomy (OVX)-induced mice, was measured by RT-qPCR. Western blot was conducted to analyze protein levels of osteogenesis-related molecules (Opg, RUNX2, ALP, BMP4) and TXNIP. RNA immunoprecipitation (RIP) and RNA pull-down assays were performed to validate the binding relationship among circ_0005753, PTBP1, and TXNIP. Alkaline phosphatase (ALP) and alizarin red staining (ARS) were performed to evaluate osteogenic capacity of BMSCs. OP mouse model was established by ovariectomy, as evaluated pathologic changes via hematoxylin-eosin (HE), Masson, and Immunohistochemistry (IHC) staining. Expression of circ_0005753 was remarkably decreased during MEL-induced osteogenic differentiation of BMSCs. Interestingly, not only circ_0005753 knockdown significantly promoted osteogenic differentiation of BMSCs, but circ_0005753 overexpression also weakened osteogenic differentiation induced by MEL treatment. Mechanistically, circ_0005753 maintained the stabilization of TXNIP mRNA via recruiting PTBP1. Additionally, reinforced circ_0005753 abrogated MEL-mediated protective effects on OP pathogenesis in a mouse model. This work shows that MEL facilitates osteogenic differentiation of BMSCs via the circ_0005753/PTBP1/TXNIP axis, which may shed light on the development of a novel therapeutic strategy to prevent OP.

Divergent trajectory of replication and intrinsic pathogenicity of SARS-CoV-2 Omicron post-BA.2/5 subvariants in the upper and lower respiratory tract.

BACKGROUND: Earlier Omicron subvariants including BA.1, BA.2, and BA.5 emerged in waves, with a subvariant replacing the previous one every few months. More recently, the post-BA.2/5 subvariants have acquired convergent substitutions in spike that facilitated their escape from humoral immunity and gained ACE2 binding capacity. However, the intrinsic pathogenicity and replication fitness of the evaluated post-BA.2/5 subvariants are not fully understood. METHODS: We systemically investigated the replication fitness and intrinsic pathogenicity of representative post-BA.2/5 subvariants (BL.1, BQ.1, BQ.1.1, XBB.1, CH.1.1, and XBB.1.5) in weanling (3-4 weeks), adult (8-10 weeks), and aged (10-12 months) mice. In addition, to better model Omicron replication in the human nasal epithelium, we further investigated the replication capacity of the post-BA.2/5 subvariants in human primary nasal epithelial cells. FINDINGS: We found that the evaluated post-BA.2/5 subvariants are consistently attenuated in mouse lungs but not in nasal turbinates when compared with their ancestral subvariants BA.2/5. Further investigations in primary human nasal epithelial cells revealed a gained replication fitness of XBB.1 and XBB.1.5 when compared to BA.2 and BA.5.2. INTERPRETATION: Our study revealed that the post-BA.2/5 subvariants are attenuated in lungs while increased in replication fitness in the nasal epithelium, indicating rapid adaptation of the circulating Omicron subvariants in the human populations. FUNDING: The full list of funding can be found at the Acknowledgements section.

Fluorescence Tracking of Small Extracellular Vesicles In Vivo.

In this study, we employed organic and inorganic dyes that have fluorescence under visible or near-infrared light region to stain human umbilical cord (Huc) mesenchymal stem cell (MSC)-, HEK293T cell- and HGC cell-derived small extracellular vesicles (sEVs), and then tracked their fluorescence signals in human gastric cancer xenografted murine models. Several biological characteristics were examined and compared when different dye-stained sEVs in the same tumor model or the same dye-stained sEVs between different tumor models were applied, including sEVs circulation in the blood, biodistribution of sEVs in major organs, and time-dependent tumor accumulation of sEVs. The results demonstrated that distinct tumor accumulation features were presented by sEVs if labeled by different fluorescent dyes, while sEVs derived from different cell lines showed homologous blood circulation and tumor accumulation. To conclude, although fluorescence imaging remains a reliable way to trace sEVs, single staining of sEVs membrane should be obviated in future work when examining the biological fate of sEVs.

Dysregulated Tfr/Tfh2 cells in patients with polycystic ovarian syndrome.

Recent research revealed the pathogenic role of B cells in the pathogenesis of polycystic ovary syndrome (PCOS), while the Tfh cell plays a critical role in the B cell mediated autoantibody production and humoral immunity, but had not been investigated in PCOS patients. The frequency of Tfh and B cell subsets (Tfh1, Tfh2, Tfh17, naïve B, memory B, and plasma cells) in the peripheral blood of 21 PCOS patients and 15 healthy controls were investigated by flow cytometry. And the levels of follicle-stimulating hormone, luteinizing hormone, testosterone, prolactin and estradiol progesterone were measured by using the immunoluminescence method. Also, the associations between these hormone levels and Tfh cell subsets or B cell subsets were analyzed. No significant difference was observed in total Tfh cells between 21 PCOS patients and 15 healthy controls (p > 0.05). But the percentages of Tfh2 and plasma cells were significantly higher in 21 PCOS patients compared to 15 healthy controls (p < 0.05). In contrast, the frequency of Tfr cells and Tfr/Tfh2 ratio were significantly lower than healthy controls (p < 0.01). Importantly, among these cells, only the percentage of Tfh2 cells was positively correlated with the levels of testosterone (r = 0.513, p = 0.018). And the percentage of Tfr cells and Tfr/Tfh2 ratio were also positively correlated with the levels of testosterone (r = 0.567, p = 0.007; r = 0.434, p = 0.05) and prolactin (r = 0.511, p = 0.018; r = 0.490, p = 0.024). These new findings provide unique insights into dysregulated Tfh/Tfr cells in mediating the immunopathogenesis of PCOS patients.

Antler-derived microRNA PC-5p-1090 inhibits HCC cell proliferation, migration, and invasion by targeting MARCKS, SMARCAD1, and SOX9.

The capability of microRNAs (miRNAs) to regulate gene expression across species has opened new avenues for miRNA-based therapeutics. Here, we investigated the potential of PC-5p-1090 (miR-PC-1090), a miRNA found in deer antlers, to control the malignant phenotypes of hepatocellular carcinoma (HCC) cells. Using Cell Counting Kit-8 and transwell assays, we found that heterologous expression of miR-PC-1090 inhibited HCC cell proliferation, migration, and invasion. Bioinformatics analysis indicated that predicted miR-PC-1090 targets, including MARCKS, SMARCAD1, and SOX9, were significantly elevated in HCC tissues, and their high expressions were associated with poor overall survival of HCC patients. Moreover, mechanistic investigations revealed that miR-PC-1090 promoted the degradation of MARCKS and SMARCAD1 mRNAs and hindered the translation of SOX9 mRNA by recognizing their 3' untranslated regions. Subsequent loss-of-function and rescue experiments confirmed the involvement of MARCKS, SMARCAD1, and SOX9 in miR-PC-1090-suppressed HCC cell proliferation, migration, and invasion. Notably, MARCKS knockdown induced the downregulation of phosphorylated MARCKS and a corresponding upregulation of phosphorylated AKT in HCC. Conversely, miR-PC-1090 repressed MARCKS phosphorylation and effectively circumvented the activation of the PI3K/AKT pathway. Furthermore, miR-PC-1090 regulates the Wnt/ß-catenin pathway through SMARCAD1- and SOX9-mediated reduction of ß-catenin expression. Overall, our results illustrate the tumor-suppressive activity and molecular mechanism of antler-derived miR-PC-1090 in HCC cells, indicating its potential as a multiple-target agent for HCC treatment.

Association between glycosylated hemoglobin levels, diabetes duration, and left ventricular diastolic dysfunction in patients with type 2 diabetes and preserved ejection fraction: a cross-sectional study.

Background: We aimed to explore the intricate interplay between glycated hemoglobin (HbA1C) levels, disease duration, and left ventricular diastolic dysfunction in patients with type 2 diabetes mellitus (T2DM) characterized by preserved ejection fraction. Methods: A cross-sectional study was conducted at the Second Affiliated Hospital of Hebei Medical University from January 2022 to December 2022. A total of 114 inpatients from the Department of Endocrinology were randomly selected based on the inclusion and exclusion criteria. Patients with T2DM were stratified into three subgroups, each comprising 38 patients, based on disease duration and HbA1C levels. A sub-analysis was conducted to explore variations among these three distinct groups. A control group comprised 38 age, gender, body mass index (BMI), and smoking habit-matched healthy volunteers form the Physical Examination Center of the same hospital. General demographic information, biochemical results, and echocardiographic data were collected, and correlation and linear regression analyses were performed. Results: Diabetic patients exhibited lower E/A values (0.85 (0.72, 1.17) vs. 1.20 (0.97, 1.30)) and elevated E/e' values (9.50 (8.75, 11.00) vs. 9.00 (7.67, 9.85)) compared to their normal controls. In the subgroup analysis, patients with a disease duration exceeding 2 years displayed reduced E/A values (0.85 (0.75, 1.10) vs. 1.10 (0.80, 1.30)) and elevated E/e' values (9.80 (9.20, 10.80) vs. 8.95 (7.77, 9.50)) in comparison to those with a disease duration of ≤2 years, p<0.05. Among patients with a disease duration surpassing 2 years, those with higher HbA1C levels exhibited lower E/A values (0.80 (0.70, 0.90) vs. (0.85 (0.75, 1.10)) and higher E/e' values (11.00 (9.87, 12.15) vs. 9.80 (9.20, 10.80)) in contrast to patients with low HbA1C levels, p<0.05. Multiple linear regression analysis identified HbA1C (ß=0.294, p<0.001) and disease duration (ß=0.319, p<0.001) as independent risk factors for the E/A value in diabetes patients. Furthermore, HbA1C (ß=0.178, p=0.015) and disease duration (ß=0.529, p<0.001) emerged as independent risk factors for the E/e' value in diabetic patients. Conclusions: In individuals with T2DM exhibiting preserved ejection fraction, the presence of left ventricular diastolic dysfunction is significantly associated with HbA1C levels and the duration of diabetes.

RNA sequencing-based identification of microRNAs in the antler cartilage of Gansu red deer (Cervus elaphus kansuensis).

Background: The velvet antler is a complex mammalian bone organ with unique biological characteristics, such as regeneration. The rapid growth stage (RGS) is a special period in the regeneration process of velvet antler. Methods: To elucidate the functions of microRNAs (miRNAs) at the RGS of antler development in Gansu red deer (Cervus elaphus kansuensis), we used RNA sequencing (RNA-seq) to analyze miRNA expression profiles in cartilage tissues of deer antler tips at three different growth stages. Results: The RNA-seq results revealed 1,073 known and 204 novel miRNAs, including 1,207, 1,242, and 1,204 from 30-, 60-, and 90-d antler cartilage tissues, respectively. To identify key miRNAs controlling rapid antler growth, we predicted target genes of screened 25 differentially expressed miRNAs (DEMs) and specifically expressed miRNAs (SEMs) in 60 d and annotated their functions. The KEGG results revealed that target genes of 25 DEMs and 30 SEMs were highly classified in the "Metabolic pathways", "Pathways in cancer", "Proteoglycans in cancer" and "PI3K-Akt signaling pathway". In addition, a novel miRNA (CM008039.1_315920), highly enriched in "NF-kappa B signaling pathway", may need further study. Conclusions: The miRNAs identified in our study are potentially important in rapid antler growth. Our findings provide new insights to help elucidate the miRNA-mediated regulatory mechanisms involved during velvet antler development in C. elaphus kansuensis.

The clinical performance of ultra-low-dose shoulder CT scans: The assessment on image and physical 3D printing models.

OBJECTIVES: Evaluation of the clinical performance of ultra-low-dose computed tomography (CT) images of the shoulder joint on image-based diagnosis and three-dimensional (3D) printing surgical planning. MATERIALS AND METHODS: A total of 93 patients with displaced shoulder fractures were randomly divided into standard-dose, low-dose, and ultra-low-dose groups. Three-dimensional printing models of all patients' shoulder joints were fabricated. The subjective image quality and 3D-printing model were evaluated by two senior orthopedic surgeons who were blinded to any scanning setting. A 3-point scale system was used to quantitatively assess the image quality and 3D printing model, where more than 2 points meant adequate level for clinical application. RESULTS: Compared with the standard dose protocol, ultra-low-dose technique reduced the radiation dose by 99.29% without loss of key image quality of fracture pattern. Regarding the subjective image quality, the assessment scores for groups of standard, low, and ultra-low doses were 3.00, 2.76, 2.00 points on scapula and humerus, and 3.00, 2.73, 2.44 points on clavicle. Scores of the three groups for the assessment of 3D printing models were 3.00, 2.80, 1.34 on scapula and humerus, and 3.00, 2.90, 2.06 on clavicle. In the ultra-low-dose group, 24 out of 33 (72.7%) 3D printing models of scapula and humerus received lower than 2 points of the evaluation score, while nearly 94% of the clavicle models reached the adequate level. CONCLUSION: An ultra-low-dose protocol is adequate for the diagnosis of either displaced or non-displaced fractures of the shoulder joint even though minor flaws of images are present. Three-dimensional printing models of shoulder joints created from ultra-low-dose CT scans can be used for surgical planning at specific bone like the clavicle but perform insufficiently in the overall surgical planning for shoulder injuries due to the significant geometric flaws.

Feasibility study of three-dimensional printing knee model using the ultra-low-dose CT scan for preoperative planning and simulated surgery.

OBJECTIVE: To explore the feasibility of the three-dimensional printing (3DP) knee model using the ultra-low-dose computed tomography (CT) scan for preoperative planning and simulated surgery. METHODS: Thirty-six patients were divided into the standard-dose protocol group (A) and ultra-low-dose protocol group (B). The anteroposterior diameter, left and right diameter of femur, anteroposterior diameter of tibial plateau (APTP), left and right diameter, distance from the intercondylar ridge to tibial tuberosity, lower femur angle, and upper tibial angle were measured on CT images. On the 3D printed knee joint model, Vernier calipers were used to measure: anteroposterior diameter, left and right diameter of the internal and external condyles of femur; left and right diameters, anteroposterior diameters of tibial plateau; upper and lower meridian, left and right diameters of patella. RESULTS: With group A as reference, the effective radiation dose in group B was significantly reduced to 97.0% (36.4 ± 3.7 uSv and 1.1 ± 0.2 uSv, respectively). There was no difference in objective parameters for 3DP model (p = 0.31-0.84). None of the quantitative parameters of image quality showed significant difference (p = 0.11-0.96). Despite lower score of image quality and 3DP model in group B (3.0 ± 0.0 vs. 2.1 ± 0.2, 2.9 ± 0.3 vs. 2.2 ± 0.4; p < 0.05), the diagnostic performance was consistent in the two groups (all scores ≥ 2). Image quality and 3DP printed models were highly consistent (k = 0.97). CONCLUSIONS: Ultra-low-dose protocol reduces the radiation dose while maintaining the image quality of knee. It meets the requirement for 3DP model, internal fixation model selection, and simulated surgery.

Kruppel Like Factor 5 Enhances High Glucose-Induced Renal Tubular Epithelial Cell Transdifferentiation in Diabetic Nephropathy.

Background - Diabetic nephropathy (DN) is a principal reason for kidney disease worldwide. High glucose (HG) is a major factor for DN. Kruppel like factor 5 (KLF5) participates in DN development. In the present study, we aim to elaborate the role of KLF5 in HG-induced renal tubular epithelial cell (RTEC) transdifferentiation in DN. Methods - RTECs (HK-2 cells) were treated with HG and were transfected with si-KLF5 or oe-HMGB1. Afterwards, expression of KLF5 and HMGB1 was detected, HK cell viability was determined, and levels of alpha-smooth muscle actin (α-SMA), E-cadherin, vimentin, and transforming growth factor beta 1 (TGF-ß1) were assessed. Additionally, the binding relation between KLF5 and HMGB1 was analyzed. Results - In HK-2 cells with HG treatment, expression of KLF5 and HMGB1 was upregulated; levels of α-SMA, vimentin, and TGF-ß1 were increased; and E-cadherin level was decreased. Moreover, KLF5 silencing resulted in down-regulated levels of α-SMA, vimentin, and TGF-ß1 but upregulated level of E-cadherin. On the other hand, KLF5 could bind to the HMGB1 promoter and activate HMGB1 transcription. HMGB1 overexpression partially counteracted the inhibitive effect of KLF5 silencing on HG-induced HK-2 transdifferentiation. Conclusion - HG induced overexpressed KLF5 in RTECs, and as a transcription factor, KLF5 could bind to the HMGB1 promoter, thereby promoting HMGB1 transcription and RTEC transdifferentiation.

The effect of Bushen Culuan Decoction on anovulatory infertile women among 6 different diseases: a study protocol for a randomized, double-blinded, positively controlled, adaptive multicenter clinical trial.

BACKGROUND: Anovulation is one of the main causes of female infertility. This study will evaluate the effectiveness and safety of Bushen Culuan Decoction for anovulatory infertility caused by six diseases, including anovulatory abnormal uterine bleeding, polycystic ovarian syndrome, hyperprolactinemia, luteinized unruptured follicle syndrome, corpus luteum insufficiency, and premature ovarian insufficiency. METHODS: This is a randomized, double-blinded, double-dummy, parallel, positively controlled, adaptive, multicenter clinical trial. All participants will be randomly allocated by a central randomization system to the treatment group or the control group in a 1:1 ratio. The treatment group will undergo a 14-day treatment with Bushen Culuan Decoction 13 g three times a day and a 5-day treatment with clomiphene citrate placebo tablets 50 mg once a day starting on day 5 of every menstrual period. The control group will undergo a 14-day treatment with Bushen Culuan Decoction placebo 13 g three times a day and a 5-day treatment with clomiphene citrate tablets 50 mg once a day from day 5 in every menstrual period. The whole treatment will last through 3 menstrual periods or 6 menstrual periods, depending on whether ovulation is regained in the first 3 menstrual periods. All statistical analyses will be performed in SPSS 21.0 (SPSS, Chicago, Illinois, USA), and a p value < 0.05 will be considered statistically significant. DISCUSSION: The objective of this RCT is to evaluate whether Bushen Culuan Decoction enables a higher pregnancy rate than clomiphene citrate in women with anovulatory infertility and to identify the anovulatory diseases for which Bushen Culuan Decoction has higher effectiveness .This study has been approved by the Medical Ethics Committee of Xiyuan Hospital China Academy of Chinese Medical Sciences (No. 2017XLA037-2). The results of this study will be offered for publication in peer-reviewed journals. TRIAL REGISTRATION: ClinicalTrials.gov NCT03709849 . Registered on 19 November 2018.

Role of Tfh17 cells in patients with multiple myeloma.

Objective Follicular helper T cells (Tfh) drive proliferation and differentiation of B cells into plasma cells, leading to antibody production; however, their role in multiple myeloma (MM) is unknown. We aimed to determine the alteration of Tfh subsets and their clinical significance in patients with MM.Method Forty-nine patients with MM were recruited in this study, including 12 newly diagnosed patients, 10 relapsed patients, and 8 patients who received autologous hematopoietic stem cell transplantation (ASCT) from Zhejiang Provincial People's Hospital. Total CD4 + CXCR5 + CD25lowCD127intermediate-high Tfh cells, CXCR3 + CCR6-Tfh1 cells, CXCR3-CCR6-Tfh2 cells, and CXCR3-CCR6 + Tfh17 cells from the peripheral blood of these patients were analyzed by flow cytometry.Result Although total Tfh cells were not significantly changed in patients with MM compared to that in healthy controls (HCs), the Tfh17/Tfh ratio was significantly elevated in patients with MM compared to that in HCs (P = 0.0001). Importantly, relapsed patients had higher Tfh17/Tfh ratio than the newly diagnosed patients (P = 0.0077). Moreover, the Tfh17/Tfh ratio was significantly decreased in patients with MM who received ASCT (post-ASCT) when compared to that in HCs and non-ASCT patients (P < 0.0001), but no change was observed between post-ASCT patients and HCs (P = 0.7498).Conclusion The Tfh17/Tfh ratio was significantly elevated in patients with MM, especially in relapsed patients, indicating that Tfh17 cells may play a critical role in the clinical progression of MM.

Association Between Psoriasis and Nonalcoholic Fatty Liver Disease Among Outpatient US Adults.

Importance: Recent studies have shown an association between psoriasis and nonalcoholic fatty liver disease (NAFLD) in US inpatients, but the association is still unclear in the outpatient US population. Objective: To assess whether psoriasis is associated with NAFLD in outpatient US adults. Design, Setting, and Participants: This population-based cross-sectional study used data on US adults aged 20 to 59 years from the National Health and Nutrition Examination Survey (NHANES) 2003-2006 and 2009-2014 cycles. Data were analyzed from June to September 2021. Exposures: Self-reported psoriasis. Main Outcomes and Measures: The main outcome was NAFLD, defined as a US fatty liver index score greater than 30. Sampling weights were calculated according to NHANES guidelines. Results: Among 5672 adults included in this study (mean age, 38.9 years [95% CI, 38.4-39.3 years]; 2999 [51.1%] female), 148 (3.0%) had psoriasis and 5524 (97.0%) did not have psoriasis. A total of 1558 participants (26.8%) were classified as having NAFLD. Compared with participants without psoriasis, those with psoriasis had a higher prevalence of NAFLD (32.7% [52] vs 26.6% [1506]). In a multivariable logistic regression model adjusted for age, sex, race and ethnicity, educational level, family income, marital status, NHANES cycles, diabetes, metabolic syndrome, and smoking and alcohol drinking status, psoriasis was associated with NAFLD (odds ratio [OR], 1.67; 95% CI, 1.03-2.70). In subgroup analyses, psoriasis was associated with NAFLD among men (OR, 2.16; 95% CI, 1.10-4.24), among those aged 20 to 39 years (OR, 2.48; 95% CI, 1.09-5.67), and among those without diabetes (1.70; 95% CI, 1.05-2.76). An association between psoriasis and NAFLD was found in sensitivity analyses that excluded potential hepatotoxic medication use (OR, 1.72; 95% CI, 1.01-2.95) or non-Hispanic Black participants (OR, 1.76; 95% CI, 1.07-2.87), redefined NAFLD based on the hepatic steatosis index score (OR, 1.59; 95% CI, 1.01-2.50), and used inverse probability of treatment weighting (OR, 1.43; 95% CI, 1.09-1.86). Conclusions and Relevance: In this cross-sectional study, psoriasis was associated with NAFLD in the outpatient US adult population in adjusted models. This association may be important to consider in the context of clinicians prescribing potentially hepatotoxic medication for psoriasis management.

Integrative Analyses of Antler Cartilage Transcriptome and Proteome of Gansu Red Deer (Cervus elaphus kansuensis) at Different Growth Stages.

The velvet antler is a unique model for cancer and regeneration research due to its periodic regeneration and rapid growth. Antler growth is mainly triggered by the growth center located in its tip, which consists of velvet skin, mesenchyme and cartilage. Among them, cartilage accounts for most of the growth center. We performed an integrative analysis of the antler cartilage transcriptome and proteome at different antler growth stages. RNA-seq results revealed 24,778 unigenes, 19,243 known protein-coding genes, and 5535 new predicted genes. Of these, 2722 were detected with differential expression patterns among 30 d, 60 d, and 90 d libraries, and 488 differentially expressed genes (DEGs) were screened at 30 d vs. 60 d and 60 d vs. 90 d but not at 30 d vs. 90 d. Proteomic data identified 1361 known proteins and 179 predicted novel proteins. Comparative analyses showed 382 differentially expressed proteins (DEPs), of which 16 had differential expression levels at 30 d vs. 60 d and 60 d vs. 90 d but not at 30 d vs. 90 d. An integrated analysis conducted for DEGs and DEPs showed that gene13546 and its coding protein protein13546 annotated in the Wnt signaling pathway may possess important bio-logical functions in rapid antler growth. This study provides in-depth characterization of candidate genes and proteins, providing further insights into the molecular mechanisms controlling antler development.