Correlation between abdominal computed tomography signs and postoperative prognosis for patients with colorectal cancer.

BACKGROUND: Patients with different stages of colorectal cancer (CRC) exhibit different abdominal computed tomography (CT) signs. Therefore, the influence of CT signs on CRC prognosis must be determined. AIM: To observe abdominal CT signs in patients with CRC and analyze the correlation between the CT signs and postoperative prognosis. METHODS: The clinical history and CT imaging results of 88 patients with CRC who underwent radical surgery at Xingtan Hospital Affiliated to Shunde Hospital of Southern Medical University were retrospectively analyzed. Univariate and multivariate Cox regression analyses were used to explore the independent risk factors for postoperative death in patients with CRC. The three-year survival rate was analyzed using the Kaplan-Meier curve, and the correlation between postoperative survival time and abdominal CT signs in patients with CRC was analyzed using Spearman correlation analysis. RESULTS: For patients with CRC, the three-year survival rate was 73.86%. The death group exhibited more severe characteristics than the survival group. A multivariate Cox regression model analysis showed that body mass index (BMI), degree of periintestinal infiltration, tumor size, and lymph node CT value were independent factors influencing postoperative death (P < 0.05 for all). Patients with characteristics typical to the death group had a low three-year survival rate (log-rank χ 2 = 66.487, 11.346, 12.500, and 27.672, respectively, P < 0.05 for all). The survival time of CRC patients was negatively correlated with BMI, degree of periintestinal infiltration, tumor size, lymph node CT value, mean tumor long-axis diameter, and mean tumor short-axis diameter (r = -0.559, 0.679, -0.430, -0.585, -0.425, and -0.385, respectively, P < 0.05 for all). BMI was positively correlated with the degree of periintestinal invasion, lymph node CT value, and mean tumor short-axis diameter (r = 0.303, 0.431, and 0.437, respectively, P < 0.05 for all). CONCLUSION: The degree of periintestinal infiltration, tumor size, and lymph node CT value are crucial for evaluating the prognosis of patients with CRC.

[Comparison of multi-type chemical compounds in fruits of Lycium and correlations between compounds and traits].

To comprehensively reveal and utilize the plant resources of Lycium in China, this study determined and compared the content of monosaccharides, polysaccharides, proteins, carotenoids, organic acids, and phenols in the dried fruits of 8 different Lycium species. Furthermore, the traits including the hundred-fruit weight, shape index, and the ratio of seed to fruit were measured, and the correlations between the content of chemical compounds and fruit traits were assessed. The results showed that L. truncatum, L. barbarum var. auranticarpum, and L. dasystemum var. rubricaulium were the species with high content of monosaccharides. L. barbarum and L. barbarum var. auranticarpum were the species with high content of total polysaccharides, and L. barbarum was the species with high content of carotenoids. L. yunnanense and L. chinense var. potaninii had high content of soluble proteins. L. truncatum, L. dasystemum, and L. barbarum showed high content of organic acids and phenols. L. barbarum and L. barbarum var. auranticarpum demonstrated high fruit weight, while L. yunnanense and L. chinense had high ratios of seed to fruit. The multivariate statistical analysis indicated that polysaccharides, carotenoids, hundred-fruit weight, ratio of seed to fruit, scopolamine, fructose, 5-O-feruloylquinic acid, kaempferol-3-O-rutinoside, scopoletin, cryptochlorogenic acid, and caffeic acid were the main differential compounds in the fruits among different species of Lycium. Moreover, the results of correlation ananysis showed strong correlations between fruit traits and compound content. Specifically, the hundred-fruit weight had positive correlations with the content of total polysaccharides and scopola-mine. The ratio of seed to fruit was negatively correlated with the content of rutin, kaempferol-3-O-rutinoside, fructose, and glucose and positively correlated with the content of succinic acid, soluble proteins, and zeaxanthin. The results implied that chemical compounds presented different distribution patterns in the fruits of 8 Lycium species. This study provides a basis for the comprehensive development and utilization, targeted breeding, and value-added application of Lycium plants.

The Impact of Obesity on Diabetes Onset and Neovascularization in Mouse Models of Metabolic Stress.

Animal models of metabolic disorders are essential to studying pathogenic mechanisms and developing therapies for diabetes, but the induction protocols vary, and sexual dimorphism often exists. In a chronic diabetic model of diet-induced obesity (DIO) and low-dose streptozotocin (STZ)-induced hyperglycemia, blood glucose and lipid profiles were measured. The high-fat (HF) diet damaged insulin sensitivity and increased triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol, and liver lipid deposition. STZ increased blood glucose and liver fibrosis with less effects on blood lipids or liver lipid deposition. The combination of DIO and STZ treatments led to significant liver lipid deposition and fibrosis. Female mice showed delayed body weight gain on HF diet and resisted STZ-induced hyperglycemia. However, once they developed DIO, which occurs around 26 weeks of HF diet, the female mice were prone to STZ-induced hyperglycemia. In hindlimb ischemia, male mice in the DIO-STZ group showed significantly worse neovascularization compared with DIO or STZ groups. The DIO-STZ females showed significantly worse recovery than the DIO-STZ males. Our observations suggest that DIO-STZ is a plausible model for studying metabolic and cardiovascular disorders in obesity and diabetes. Moreover, the findings in female animals stress the need to assess sexual dimorphism and investigate the underlying mechanisms that contribute to the worse vasculopathy manifestations in females in metabolic models.

Catalpol from Rehmannia glutinosa regulates senescence in ATDC5 chondrocytes / 中国组织工程研究

BACKGROUND:The results of in vivo and in vitro studies showed that catalpol from Rehmannia glutinosa can significantly reduce the level of inflammatory indexes in the synovial tissue of rats with knee osteoarthritis,and meanwhile,it can delay the progression of knee osteoarthritis.But whether catalpol from Rehmannia glutinosa affects chondrocyte senescence and then delay the progression of knee osteoarthritis has not yet been clarified. OBJECTIVE:To investigate investigate whether catalpol from Rehmannia glutinosa could regulate ATDC5 chondrocyte senescence and the possible mechanisms. METHODS:ATDC5 chondrocytes were divided into blank group(0.1%bovine serum albumin),model group(0.1%bovine serum albumin+1 μmol/L adriamycin),low-dose catalpol group(0.1%bovine serum albumin+1 μmol/L adriamycin+20 μmol/L catalpol from Rehmannia glutinosa)and high-dose catalpol group(0.1%bovine serum albumin+1 μmol/L adriamycin+80 μmol/L catalpol from Rehmannia glutinosa).Adriamycin-induced ATDC5 chondrocyte senescence model was constructed,and the corresponding treatments were given according to the above groups.Cell counting kit-8 assay was used to detect the effects of catalpol from Rehmannia glutinosa on ATDC5 chondrocyte viability,and to screen the optimal concentration of catalpol from Rehmannia glutinosa.The senescence of ATDC5 chondrocytes in each group was detected by β-galactosidase staining after the corresponding treatments.Real-time fluorescence quantitative PCR and western blot were used to detect the mRNA and protein expression of P21,P53,type II collagen,matrix metalloproteinase 13,and interleukin-6.Immunofluorescence method was used to detect the expression of P21,P53 and type II collagen.Flow cytometry was used to detect apoptosis in each group. RESULTS AND CONCLUSION:ATDC5 chondrocytes were identified to be successfully induced and senescence model was induced.Catalpol from Rehmannia glutinosa at the concentrations of 0,20,40,and 80 μmol/L showed no significant effects on the cell viability,suggesting that catalpol from Rehmannia glutinosa is non-cytotoxic and can be used safely(P>0.05);when the concentration was≥100 μmol/L,the cell viability was reduced,suggesting that there may be cytotoxic.Therefore,80 μmol/L was chosen as the high dose for subsequent experiments in this study.The percentage of positive cells in the model group was(86.93±2.18)%,which was significantly higher than that in the blank group[(17.32±0.72)%;P<0.05].Compared with the model group,the percentage of positive cells was significantly lower in the low-and high-dose catalpol groups[(57.28±1.73)%and(27.18±0.97)%,respectively;both P<0.05].Compared with the model group,the relative expression of P21,P53,matrix metalloproteinase 13,and interleukin-6 at mRNA and protein levels was significantly downregulated in the low-and high-dose catalpol groups,while the relative expression of type II collagen at mRNA and protein levels was significantly upregulated in both groups(P<0.05),especially in the high-dose catalpol group(P<0.05).Compared with the model group,the fluorescence intensities of P21 and P53 were significantly weakened in the low-and high-dose catalpol groups,while the fluorescence intensity of type II collagen was significantly enhanced in the low-and high-dose catalpol groups(P<0.05),especially in the high-dose catalpol group(P<0.05).The cell apoptosis detected by Annexin V/PI method showed that there was no significant difference between the model group and the blank group(P>0.05);compared with the model group,the apoptotic index was significantly elevated in the low-and high-dose catalpol groups,especially in the high-dose catalpol group(P<0.05).To conclude,catalpol from Rehmannia glutinosa can slow the progression of osteoarthritis by promoting apoptosis of senescent ATDC5 chondrocytes,further removing senescent ATDC5 chondrocytes,and decreasing the senescence-associated phenotypes.

Comparative analysis of human respiratory syncytial virus evolutionary patterns during the COVID-19 pandemic and pre-pandemic periods.

The COVID-19 pandemic has resulted in the implementation of strict mitigation measures that have impacted the transmission dynamics of human respiratory syncytial virus (HRSV). The measures also have the potential to influence the evolutionary patterns of the virus. In this study, we conducted a comprehensive analysis comparing genomic variations and evolving characteristics of its neutralizing antigens, specifically F and G proteins, before and during the COVID-19 pandemic. Our findings showed that both HRSV A and B exhibited an overall chronological evolutionary pattern. For the sequences obtained during the pandemic period (2019-2022), we observed that the HRSV A distributed in A23 genotype, but formed into three subclusters; whereas the HRSV B sequences were relatively concentrated within genotype B6. Additionally, multiple positively selected sites were detected on F and G proteins but none were located at neutralizing antigenic sites of the F protein. Notably, amino acids within antigenic site III, IV, and V of F protein remained strictly conserved, while some substitutions occurred over time on antigenic site Ø, I, II and VIII; substitution S389P on antigenic site I of HRSV B occurred during the pandemic period with nearly 50% frequency. However, further analysis revealed no substitutions have altered the structural conformations of the antigenic sites, the vial antigenicity has not been changed. We inferred that the intensive public health interventions during the COVID-19 pandemic did not affect the evolutionary mode of HRSV.

Latent profile analysis and influencing factors of quality of life in pregnant women with gestational diabetes mellitus.

PURPOSE: Gestational diabetes mellitus (GDM) negatively affects the quality of life of pregnant women and is influenced by several factors. Research to date treats pregnant women with gestational diabetes as a homogeneous group based on their quality of life. We attempted to identify subgroups based on self-reported quality of life and explored variables associated with subgroups. METHODS: From September 1, 2020 to November 29, 2020, pregnant women with GDM from two hospitals in Guangdong Province were selected as subjects by convenience sampling method. Medical records provided sociodemographic data, duration of GDM, pregnancy status, and family history of diabetes. Participants completed validated questionnaires for quality of life, anxiety and depression. Latent profile analysis was used to identify profiles of quality of life in pregnant women with GDM, and then a mixed regression method was used to analyze the influencing factors of different profiles. RESULTS: A total of 279 valid questionnaires were collected. The results of the latent profile analysis showed that the quality of life of pregnant women with GDM could be divided into two profiles: C1 "high worry-high support" group (75.6%) and C2 "low worry-low support" group (24.4%). Daily exercise duration and depression degree are negative influencing factors, making it easier to enter the C1 group (p < 0.05). Disease duration and family history of diabetes are positive influencing factors, making it easier to enter the C2 group (p < 0.05). CONCLUSION: The quality of life of pregnant women with GDM had obvious classification characteristics. Pregnant women with exercise habits and depression are more likely to enter the "high worry-high support" group, and health care providers should guide their exercise according to exercise guidelines during pregnancy and strengthen psychological intervention. Pregnant women with a family history of diabetes and a longer duration of the disease are more likely to fall into the "low worry-low support" group. Healthcare providers can strengthen health education for them and improve their disease self-management abilities.

IL-38 alleviates airway remodeling in chronic asthma via blocking the profibrotic effect of IL-36γ.

Airway remodeling is a major feature of asthma. Interleukin (IL)-36γ is significantly upregulated and promotes airway hyper-responsiveness (AHR) in asthma, but its role in airway remodeling is unknown. Here, we aimed to investigate the role of IL-36γ in airway remodeling, and whether IL-38 can alleviate airway remodeling in chronic asthma by blocking the effects of IL-36γ. IL-36γ was quantified in mice inhaled with house dust mite (HDM). Extracellular matrix (ECM) deposition in lung tissues and AHR were assessed following IL-36γ administration to mice. Airway inflammation, AHR, and remodeling were evaluated after IL-38 or blocking IL-36 receptor (IL-36R) treatment in asthmatic mice. The effects of lung fibroblasts stimulated with IL-36γ and IL-38 were quantified in vitro. Increased expression of IL-36γ was detected in lung tissues of HDM-induced asthmatic mice. The intratracheal instillation of IL-36γ to mice significantly enhanced the ECM deposition, AHR, and the number of activated lung fibroblasts around the airways. IL-38 or blocking IL-36R treated asthmatic mice showed a significant alleviation in the airway inflammation, AHR, airway remodeling, and number of activated fibroblasts around airways as compared with the HDM group. In vitro, IL-36γ promoted the activation and migration of human lung fibroblasts (HFL-1). The administration of IL-38 can counteract these biological processes induced by IL-36γ in HFL-1cells. The results indicated that IL-38 can mitigate airway remodeling by blocking the profibrotic effects of IL-36γ in chronic asthma. IL-36γ may be a new therapeutic target, and IL-38 is a potential candidate agent for inhibiting airway remodeling in asthma.

Serum granulosa cell-derived TNF-α promotes inflammation and apoptosis of renal tubular cells and PCOS-related kidney injury through NF-κB signaling.

Polycystic ovary syndrome (PCOS) is a disorder with endocrinal and metabolic problems in reproductive aged women. Evidence shows that PCOS is in a high prone trend to develop kidney diseases. In this study, we investigated the mediators responsible for PCOS-related kidney injury. We found that tumor necrosis factor (TNF-α) levels were significantly increased in serum and primary cultured granulosa cells (GCs) from PCOS patients. Serum TNF-α levels were positively correlated with serum testosterone and luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio, suggesting its positive role in the severity of PCOS. Serum TNF-α levels were also positively correlated with the levels of urinary KapU, LamU, α1-MU and ß2-MU, the markers for renal tubular cell-derived proteinuria. We established a PCOS mouse model by resection of the right kidney, followed by daily administration of dihydrotestosterone (DHT, 27.5 µg, i.p.) from D7 for 90 days. We found that TNF-α levels were significantly increased in the ovary and serum of the mice, accompanied by increased renal tubular cell apoptosis, inflammation and fibrosis in kidneys. Furthermore, the receptor of TNF-α, tumor necrosis factor receptor 1 (TNFR1), was significantly upregulated in renal tubular cells. We treated human ovarian granulosa-like tumor cells (KGN) with DHT (1 µg/ml) in vitro, the conditioned medium derived from the granulosa cell culture greatly accelerated apoptotic injury in human proximal tubular epithelial cells (HKC-8), which was blocked after knockdown of TNF-α in KGN cells. Furthermore, knockdown of TNFR1 in renal tubular epithelial cells greatly ameliorated cell injury induced by granulosa cell-derived conditioned medium. These results suggest that serum TNF-α plays a key role in mediating inflammation and apoptosis in renal tubular cells associated with PCOS-related kidney injury.

Combining stable isotope, multielement and untargeted metabolomics with chemometrics to discriminate the geographical origins of ginger (Zingiber officinale Roscoe).

Ginger (Zingiber officinale Roscoe) is a high-value food and herb worldwide. The quality of ginger is often related to its production regions. In this study, stable isotopes, multiple elements, and metabolites were investigated together to realize ginger origin traceability. Chemometrics showed that ginger samples could be preliminarily separated, and 4 isotopes (δ13C, δ2H, δ18O, and δ34S), 12 mineral elements (Rb, Mn, V, Na, Sm, K, Ga, Cd, Al, Ti, Mg, and Li), 1 bioelement (%C), and 143 metabolites were the most important variables for discrimination. Furthermore, three algorithms were introduced, and the fused dataset based on VIP features led to the highest accuracies for origin classification, with predictive rates of 98% for K-nearest neighbor and 100% for support vector machine and random forest. The results demonstrated that isotopic, elemental, and metabolic fingerprints were useful indicators for the geographical origins of Chinese ginger.

Quantitative Proteomics Reveals Transforming Growth Factor ß Receptor Targeted by Resveratrol and Hesperetin Coformulation in Endothelial Cells.

The endothelium is the frontline target of multiple metabolic stressors and pharmacological agents. As a consequence, endothelial cells (ECs) display highly dynamic and diverse proteome profiles. We describe here the culture of human aortic ECs from healthy and type 2 diabetic donors, the treatment with a small molecular coformulation of trans-resveratrol and hesperetin (tRES+HESP), followed by proteomic analysis of whole-cell lysate. A number of 3666 proteins were presented in all of the samples and thus further analyzed. We found that 179 proteins had a significant difference between diabetic ECs vs. healthy ECs, while 81 proteins had a significant change upon the treatment of tRES+HESP in diabetic ECs. Among them, 16 proteins showed a difference between diabetic ECs and healthy ECs and the difference was reversed by the tRES+HESP treatment. Follow-up functional assays identified activin A receptor-like type 1 and transforming growth factor ß receptor 2 as the most pronounced targets suppressed by tRES+HESP in protecting angiogenesis in vitro. Our study has revealed the global differences in proteins and biological pathways in ECs from diabetic donors, which are potentially reversible by the tRES+HESP formula. Furthermore, we have identified the TGFß receptor as a responding mechanism in ECs treated with this formula, shedding light on future studies for deeper molecular characterization.

Identifying therapeutic biomarkers of zoledronic acid by metabolomics.

Zoledronic acid (ZOL) is a potent antiresorptive agent that increases bone mineral density (BMD) and reduces fracture risk in postmenopausal osteoporosis (PMOP). The anti-osteoporotic effect of ZOL is determined by annual BMD measurement. In most cases, bone turnover markers function as early indicators of therapeutic response, but they fail to reflect long-term effects. We used untargeted metabolomics to characterize time-dependent metabolic shifts in response to ZOL and to screen potential therapeutic markers. In addition, bone marrow RNA-seq was performed to support plasma metabolic profiling. Sixty rats were assigned to sham-operated group (SHAM, n = 21) and ovariectomy group (OVX, n = 39) and received sham operation or bilateral ovariectomy, respectively. After modeling and verification, rats in the OVX group were further divided into normal saline group (NS, n = 15) and ZOL group (ZA, n = 18). Three doses of 100 µg/kg ZOL were administrated to the ZA group every 2 weeks to simulate 3-year ZOL therapy in PMOP. An equal volume of saline was administered to the SHAM and NS groups. Plasma samples were collected at five time points for metabolic profiling. At the end of the study, selected rats were euthanatized for bone marrow RNA-seq. A total number of 163 compound were identified as differential metabolites between the ZA and NS groups, including mevalonate, a critical molecule in target pathway of ZOL. In addition, prolyl hydroxyproline (PHP), leucyl hydroxyproline (LHP), 4-vinylphenol sulfate (4-VPS) were identified as differential metabolites throughout the study. Moreover, 4-VPS negatively correlated with increased vertebral BMD after ZOL administration as time-series analysis revealed. Bone marrow RNA-seq showed that the PI3K-AKT signaling pathway was significantly associated with ZOL-mediated changes in expression (adjusted-p = 0.018). In conclusion, mevalonate, PHP, LHP, and 4-VPS are candidate therapeutic markers of ZOL. The pharmacological effect of ZOL likely occurs through inhibition of the PI3K-AKT signaling pathway.

Oxidative Stress and MicroRNAs in Endothelial Cells under Metabolic Disorders.

Reactive oxygen species (ROS) are radical oxygen intermediates that serve as important second messengers in signal transduction. However, when the accumulation of these molecules exceeds the buffering capacity of antioxidant enzymes, oxidative stress and endothelial cell (EC) dysfunction occur. EC dysfunction shifts the vascular system into a pro-coagulative, proinflammatory state, thereby increasing the risk of developing cardiovascular (CV) diseases and metabolic disorders. Studies have turned to the investigation of microRNA treatment for CV risk factors, as these post-transcription regulators are known to co-regulate ROS. In this review, we will discuss ROS pathways and generation, normal endothelial cell physiology and ROS-induced dysfunction, and the current knowledge of common metabolic disorders and their connection to oxidative stress. Therapeutic strategies based on microRNAs in response to oxidative stress and microRNA's regulatory roles in controlling ROS will also be explored. It is important to gain an in-depth comprehension of the mechanisms generating ROS and how manipulating these enzymatic byproducts can protect endothelial cell function from oxidative stress and prevent the development of vascular disorders.

Production of MSTN knockout porcine cells using adenine base-editing-mediated exon skipping.

Gene-knockout pigs have important applications in agriculture and medicine. Compared with CRISPR/Cas9 and cytosine base editing (CBE) technologies, adenine base editing (ABE) shows better safety and accuracy in gene modification. However, because of the characteristics of gene sequences, the ABE system cannot be widely used in gene knockout. Alternative splicing of mRNA is an important biological mechanism in eukaryotes for the formation of proteins with different functional activities. The splicing apparatus recognizes conserved sequences of the 5' end splice donor and 3' end splice acceptor motifs of introns in pre-mRNA that can trigger exon skipping, leading to the production of new functional proteins, or causing gene inactivation through frameshift mutations. This study aimed to construct a MSTN knockout pig by inducing exon skipping with the aid of the ABE system to expand the application of the ABE system for the preparation of knockout pigs. In this study, first, we constructed ABEmaxAW and ABE8eV106W plasmid vectors and found that their editing efficiencies at the targets were at least sixfold and even 260-fold higher than that of ABEmaxAW by contrasting the editing efficiencies at the gene targets of endogenous CD163, IGF2, and MSTN in pigs. Subsequently, we used the ABE8eV106W system to realize adenine base (the base of the antisense strand is thymine) editing of the conserved splice donor sequence (5'-GT) of intron 2 of the porcine MSTN gene. A porcine single-cell clone carrying a homozygous mutation (5'-GC) in the conserved sequence (5'-GT) of the intron 2 splice donor of the MSTN gene was successfully generated after drug selection. Unfortunately, the MSTN gene was not expressed and, therefore, could not be characterized at this level. No detectable genomic off-target edits were identified by Sanger sequencing. In this study, we verified that the ABE8eV106W vector had higher editing efficiency and could expand the editing scope of ABE. Additionally, we successfully achieved the precise modification of the alternative splice acceptor of intron 2 of the porcine MSTN gene, which may provide a new strategy for gene knockout in pigs.

Boosting UPR transcriptional activator XBP1 accelerates acute wound healing.

Patients' suffering from large or deep wounds caused by traumatic and/or thermal injuries have significantly lower chances of recapitulating lost skin function through natural healing. We tested whether enhanced unfolded protein response (UPR) by expression of a UPR transcriptional activator, X-box-binding protein 1 (XBP1) can significantly promote wound repair through stimulating growth factor production and promoting angiogenesis. In mouse models of a second-degree thermal wound, a full-thickness traumatic wound, and a full-thickness diabetic wound, the topical gene transfer of the activated form of XBP1 (spliced XBP1, XBP1s) can significantly enhance re-epithelialization and increase angiogenesis, leading to rapid, nearly complete wound closure with intact regenerated epidermis and dermis. Overexpression of XBP1s stimulated the transcription of growth factors in fibroblasts critical to proliferation and remodeling during wound repair, including platelet-derived growth factor BB, basic fibroblast growth factor, and transforming growth factor beta 3. Meanwhile, the overexpression of XBP1s boosted the migration and tube formation of dermal microvascular endothelial cells in vitro. Our functional and mechanistic investigations of XBP1-mediated regulation of wound healing processes provide novel insights into the previously undermined physiological role of the UPR in skin injuries. The finding opens an avenue to developing potential XBP1-based therapeutic strategies in clinical wound care protocols.

Tracking of Mutational Signature of SARS-CoV-2 Omicron on Distinct Continents and Little Difference was Found.

The Omicron variant is currently ravaging the world, raising serious concern globally. Monitoring genomic variations and determining their influence on biological features are critical for tracing its ongoing transmission and facilitating effective measures. Based on large-scale sequences from different continents, this study found that: (i) The genetic diversity of Omicron is much lower than that of the Delta variant. Still, eight deletions (Del 1-8) and 1 insertion, as well as 130 SNPs, were detected on the Omicron genomes, with two deletions (Del 3 and 4) and 38 SNPs commonly detected on all continents and exhibiting high-occurring frequencies. (ii) Four groups of tightly linked SNPs (linkage I-IV) were detected, among which linkage I, containing 38 SNPs, with 6 located in the RBD, increased its occurring frequency remarkably over time. (iii) The third codons of the Omicron shouldered the most mutation pressures, while the second codons presented the least flexibility. (iv) Four major mutants with amino acid substitutions in the RBD were detected, and further structural analysis suggested that the substitutions did not alter the viral receptor binding ability greatly. It was inferred that though the Omicron genome harbored great changes in antigenicity and remarkable ability to evade immunity, it was immune-pressure selected. This study tracked mutational signatures of Omicron variant and the potential biological significance of the SNPs, and the linkages await further functional verification.

Current situation and correlation analysis of professional identity and burnout among nurses in health management department / 中华健康管理学杂志

Objective:To understand the current situation of professional identity and burnout among nurses in health management department in Henan province, and analyze their correlation.Methods:This is a cross-sectional study. A general data questionnaire, the Nurse Professional Identity Scale and Nursing Burnout Scale were used to conduct an online questionnaire survey on 204 nurses from the health management departments of 6 tertiary A hospitals in Henan Province (Henan Provincial People′s Hospital, the First Affiliated Hospital of Henan University of Chinese Medicine, Henan Hospital of Traditional Chinese Medicine, Fuwai Central China Cardiovascular Hospital, Henan Chest Hospital and Zhengzhou branch of Henan Orthopedic Hospital) from March 1, 2023 to May 1, 2023. A total of 204 questionnaires were issued and 204 were recovered, with an effective rate of 100%. The correlation between professional identity and burnout was analyzed, and the general data was included into the regression equation as the control variables and the multiple linear regression analysis was carried out.Results:Among the 204 nurses in the health management department, 114 (55.9%) had a medium level and 25 (12.3%) had a low level of professional identity, 137 (67.1%) had job burnout. There was a significant negative correlation between professional identity and burnout ( r=-0.244, P<0.01). The results of multiple step-up regression showed that cognitive evaluation, frustration coping, social support, marital status, age and position were the main influencing factors of job burnout (all P<0.05). Conclusions:The professional identity and burnout of nurses in health management department are at a medium level. The higher the level of professional identity identity, the lower the burnout, and marriage, age and position were related to job burnout.

A phase III randomized, double-blind, placebo-controlled trial of the denosumab biosimilar QL1206 in postmenopausal Chinese women with osteoporosis and high fracture risk.

The current study evaluated the efficacy and safety of a denosumab biosimilar, QL1206 (60 mg), compared to placebo in postmenopausal Chinese women with osteoporosis and high fracture risk. At 31 study centers in China, a total of 455 postmenopausal women with osteoporosis and high fracture risk were randomly assigned to receive QL1206 (60 mg subcutaneously every 6 months) or placebo. From baseline to the 12-month follow-up, the participants who received QL1206 showed significantly increased bone mineral density (BMD) values (mean difference and 95% CI) in the lumbar spine: 4.780% (3.880%, 5.681%), total hip :3.930% (3.136%, 4.725%), femoral neck 2.733% (1.877%, 3.589%) and trochanter: 4.058% (2.791%, 5.325%) compared with the participants who received the placebo. In addition, QL1206 injection significantly decreased the serum levels of C-terminal crosslinked telopeptides of type 1 collagen (CTX): -77.352% (-87.080%, -66.844%), and N-terminal procollagen of type l collagen (P1NP): -50.867% (-57.184%, -45.217%) compared with the placebo over the period from baseline to 12 months. No new or unexpected adverse events were observed. We concluded that compared with placebo, QL1206 effectively increased the BMD of the lumbar spine, total hip, femoral neck and trochanter in postmenopausal Chinese women with osteoporosis and rapidly decreased bone turnover markers. This study demonstrated that QL1206 has beneficial effects on postmenopausal Chinese women with osteoporosis and high fracture risk.

Inhibition of GPR39 restores defects in endothelial cell-mediated neovascularization under the duress of chronic hyperglycemia: Evidence for regulatory roles of the sonic hedgehog signaling axis.

Impaired endothelial cell (EC)-mediated angiogenesis contributes to critical limb ischemia in diabetic patients. The sonic hedgehog (SHH) pathway participates in angiogenesis but is repressed in hyperglycemia by obscure mechanisms. We investigated the orphan G protein-coupled receptor GPR39 on SHH pathway activation in ECs and ischemia-induced angiogenesis in animals with chronic hyperglycemia. Human aortic ECs from healthy and type 2 diabetic (T2D) donors were cultured in vitro. GPR39 mRNA expression was significantly elevated in T2D. The EC proliferation, migration, and tube formation were attenuated by adenovirus-mediated GPR39 overexpression (Ad-GPR39) or GPR39 agonist TC-G-1008 in vitro. The production of proangiogenic factors was reduced by Ad-GPR39. Conversely, human ECs transfected with GPR39 siRNA or the mouse aortic ECs isolated from GPR39 global knockout (GPR39KO) mice displayed enhanced migration and proliferation compared with their respective controls. GPR39 suppressed the basal and ligand-dependent activation of the SHH effector GLI1, leading to attenuated EC migration. Coimmunoprecipitation revealed that the GPR39 direct binding of the suppressor of fused (SUFU), the SHH pathway endogenous inhibitor, may achieve this. Furthermore, in ECs with GPR39 knockdown, the robust GLI1 activation and EC migration were abolished by SUFU overexpression. In a chronic diabetic model of diet-induced obesity (DIO) and low-dose streptozotocin (STZ)-induced hyperglycemia, the GPR39KO mice demonstrated a faster pace of revascularization from hind limb ischemia and lower incidence of tissue necrosis than GPR39 wild-type (GPR39WT) counterparts. These findings have provided a conceptual framework for developing therapeutic tools that ablate or inhibit GPR39 for ischemic tissue repair under metabolic stress.