Targeting KPNB1 with Genkwadaphnin suppresses gastric cancer progression through the Nur77-mediated signaling pathway.

Gastric cancer (GC) remains a global challenge due to the lack of early detection and precision therapies. Genkwadaphnin (DD1), a natural diterpene isolated from the bud of Flos GenkWa (Thymelaeaceae), serves as a Karyopherin ß1 (KPNB1) inhibitor. In this study, we investigated the anti-tumor effect of DD1 in both cell culture and animal models. Our findings reveal that KPNB1, a protein involved in nuclear import, was highly expressed in GC tissues and associated with a poor prognosis in patients. We demonstrated that DD1, alongside the established KPNB1 inhibitor importazole (IPZ), inhibited GC cell proliferation and tumor growth by enhancing both genomic and non-genomic activity of Nur77. DD1 and IPZ reduced the interaction between KPNB1 and Nur77, resulting in Nur77 cytoplasmic accumulation and triggering mitochondrial apoptosis. The inhibitors also increased the expression of the Nur77 target apoptotic genes ATF3, RB1CC1 and PMAIP1, inducing apoptosis in GC cell. More importantly, loss of Nur77 effectively rescued the inhibitory effect of DD1 and IPZ on GC cells in both in vitro and in vivo experiments. In this study, we for the first time explored the relationship between KPNB1 and Nur77, and found KPNB1 inhibition could significantly increase the expression of Nur77. Moreover, we investigated the function of KPNB1 in GC for the first time, and the results suggested that KPNB1 could be a potential target for cancer therapy, and DD1 might be a prospective therapeutic candidate.

Effect of energy level of pullet diet and age on laying performance and expression of hypothalamus-pituitary-gonadal related genes in laying hens.

Dietary energy density influences feed intake (FI) and development of layer-type pullets. A total of 384 nine-wk-old Hy-Line Brown pullets were randomly assigned to one of 3 dietary treatments: fed a diet with 2,600, 2,750, and 2,900 Kcal metabolizable energy/kg (ME/kg) from 10 to 21 wk of age. The results showed that the 2,900 and 2,600 ME groups had lower feed and ME intake (P < 0.01) from 10 to 21 wk of age. The 2,600 ME pullets had heavier body weight (BW) and longer shank length (P < 0.05) at 21 wk of age than the 2,750 ME group. The eggshell percentage was increased by the 2,600 and 2,900 kcal/kg treatments (P = 0.002). Serum concentration of 17-ß-estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) decreased at 70 wk of age (P < 0.05). Pullet diet and its interaction with age had a significant influence (P < 0.001) on the expression of gonadotropin-releasing hormone 1 (GnRH-1) and gonadotropin-inhibitory hormone (GnIH) in the hypothalamus and of gonadotropin releasing hormone 1 receptor (GnRH-1R) and gonadotropin-inhibitory hormone receptor (GnIHR) in the pituitary. In the hypothalamus, GnRH-1 expression increased from 9 to 40 wk of age and then decreased; however, GnIH expression was highest at 70 wk of age. Follicle-stimulating hormone receptor (FSHR) expression increased (P < 0.001) at wk 40 and decreased at wk 70 compared to wk 21 at various follicular stages. In conclusion, the energy level of pullet diet had no unfavorable influence on feed intake, laying rate, egg mass, and FCR, whereas change egg weight and mortality during the laying period from 21 to 70 wk of age. during the laying period. These results suggest that pullet dietary energy can activate the expression of genes related to reproduction in the hypothalamus, whereas it plays a minor role in the regulation of genes in the pituitary and ovary. Age-induced gene expression in the hypothalamus-pituitary-gonadal (HPG) axis is associated with laying performance in hens.

Relationship between jejunum ATPase activity and antioxidant function on the growth performance, feed conversion efficiency, and jejunum microbiota in Hu sheep (Ovis aries).

BACKGROUND: ATPase activity and the antioxidant function of intestinal tissue can reflect intestinal cell metabolic activity and oxidative damage, which might be related to intestinal function. However, the specific influence of intestinal ATPase activity and antioxidant function on growth performance, feed conversion efficiency, and the intestinal microbiota in sheep remains unclear. RESULTS: This study analyzed the correlation between ATPase activity and antioxidant function in the jejunum of 92 Hu sheep and their growth performance and feed conversion efficiency. Additionally, individuals with the highest (H group) and lowest (L group) jejunum MDA content and Na+ K+-ATPase activity were further screened, and the effects of jejunum ATPase activity and MDA content on the morphology and microbial community of sheep intestines were analyzed. There was a significant correlation between jejunum ATPase and SOD activity and the initial weight of Hu sheep (P < 0.01). The H-MDA group exhibited significantly higher average daily gain (ADG) from 0 to 80 days old and higher body weight (BW) after 80 days. ATPase and SOD activities, and MDA levels correlated significantly and positively with heart weight. The jejunum crypt depth and circular muscle thickness in the H-ATP group were significantly higher than in the L-ATP group, and the villus length, crypt depth, and longitudinal muscle thickness in the H-MDA group were significantly higher than in the L-MDA group (P < 0.01). High ATPase activity and MDA content significantly reduced the jejunum microbial diversity, as indicated by the Chao1 index and observed species, and affected the relative abundance of specific taxa. Among species, the relative abundance of Olsenella umbonata was significantly higher in the H-MDA group than in the L-MDA group (P < 0.05), while Methanobrevibacter ruminantium abundance was significantly lower than in the L-MDA group (P < 0.05). In vitro culture experiments confirmed that MDA promoted the proliferation of Olsenella umbonata. Thus, ATPase and SOD activities in the jejunum tissues of Hu sheep are predominantly influenced by congenital factors, and lambs with higher birth weights exhibit lower Na+ K+-ATPase, Ca2+ Mg2+-ATPase, and SOD activities. CONCLUSIONS: The ATPase activity and antioxidant performance of intestinal tissue are closely related to growth performance, heart development, and intestinal tissue morphology. High ATPase activity and MDA content reduced the microbial diversity of intestinal tissue and affect the relative abundance of specific taxa, representing a potential interaction between the host and its intestinal microbiota.

A bibliometric analysis of interstitial cells of Cajal research.

Objective: The significance of interstitial cells of Cajal (ICC) in the gastrointestinal tract has garnered increasing attention. In recent years, approximately 80 articles on ICC have been published annually in various journals. However, no bibliometric study has specifically focused on the literature related to ICC. Therefore, we conducted a comprehensive bibliometric analysis of ICC to reveal dynamic scientific developments, assisting researchers in exploring hotspots and emerging trends while gaining a global perspective. Methods: We conducted a literature search in the Web of Science Core Collection (WoSCC) from January 1, 2013, to December 31, 2023, to identify relevant literature on ICC. We employed bibliometric software, namely VOSviewer and CiteSpace, to analyze various aspects including annual publication output, collaborations, research hotspots, current status, and development trends in this domain. Results: A total of 891 English papers were published in 359 journals by 928 institutions from 57 countries/regions. According to the keyword analysis of the literature, researchers mainly focused on "c-Kit," "expression," "smooth muscle," and "nitric oxide" related to ICC over the past 11 years. However, with "SIP syncytium," "ANO1," "enteric neurons," "gastrointestinal stromal tumors (GIST)," and "functional dyspepsia (FD)," there has been a growing interest in the relationship between ANO1, SIP syncytium, and ICC, as well as the role of ICC in the treatment of GIST and FD. Conclusion: Bibliometric analysis has revealed the current status of ICC research. The association between ANO1, SIP syncytium, enteric neurons and ICC, as well as the role of ICC in the treatment of GIST versus FD has become the focus of current research. However, further research and collaboration on a global scale are still needed. Our analysis is particularly valuable to researchers in gastroenterology, oncology, and cell biology, providing insights that can guide future research directions.

Development of family resource indicators for people with schizophrenic disorder in community by modified Delphi method in Beijing, China.

INTRODUCTION: Most people with schizophrenia in China are supported by their family members in community. The patient's family is confronted with severe care burden and pressure, which directly affects the caregiver's own health and social life, and indirectly affects the patient's rehabilitation. Adequate family resources can reduce the burden and pressure on families. But there is an absence of systematic family resource indicators for people with schizophrenic disorder in China. OBJECTIVES: This study aimed to develop a set of family resource indicators for people with schizophrenic disorder in China. DESIGN: Preliminary family resource indicators were generated and refined by literature review and an expert consultation meeting. Two rounds of email-based Delphi survey were carried out to identify family resource indicators. SETTING: Two rounds of email-based Delphi survey were performed from July to September 2021 in Beijing, China. PARTICIPANTS: There were 15 mental health doctors from community health service centres and four psychiatrists from tertiary hospitals, and two primary care researchers from universities in the first and second rounds Delphi survey. RESULTS: All the 21 experts participated in both rounds of Delphi survey. A total of 46 indicators achieved consensus for inclusion in the final set of indicators after two rounds of Delphi survey. The final set of indicators was grouped into 10 domains: financial support (three indicators), psychological and spiritual support (eight indicators), medical treatment (three indicators), information and education (three indicators), structural support (two indicators), external family resources included social resources (five indicators), cultural resources (two indicators), economic resources (seven indicators), environmental resources (four indicators) and medical resources (nine indicators). CONCLUSIONS: A set of 46 family resource indicators for people with schizophrenic disorder in community was identified by an iterative Delphi process in Beijing, China. However, the indicators still need to be validated by testing in further studies.

Sequential glycosylations at the multibasic cleavage site of SARS-CoV-2 spike protein regulate viral activity.

The multibasic furin cleavage site at the S1/S2 boundary of the spike protein is a hallmark of SARS-CoV-2 and plays a crucial role in viral infection. However, the mechanism underlying furin activation and its regulation remain poorly understood. Here, we show that GalNAc-T3 and T7 jointly initiate clustered O-glycosylations in the furin cleavage site of the SARS-CoV-2 spike protein, which inhibit furin processing, suppress the incorporation of the spike protein into virus-like-particles and affect viral infection. Mechanistic analysis reveals that the assembly of the spike protein into virus-like particles relies on interactions between the furin-cleaved spike protein and the membrane protein of SARS-CoV-2, suggesting a possible mechanism for furin activation. Interestingly, mutations in the spike protein of the alpha and delta variants of the virus confer resistance against glycosylation by GalNAc-T3 and T7. In the omicron variant, additional mutations reverse this resistance, making the spike protein susceptible to glycosylation in vitro and sensitive to GalNAc-T3 and T7 expression in human lung cells. Our findings highlight the role of glycosylation as a defense mechanism employed by host cells against SARS-CoV-2 and shed light on the evolutionary interplay between the host and the virus.

Comparison of stimulation protocols for dose determination of gonadotropins: A systematic review and Bayesian network meta-analysis based on randomized controlled trials.

BACKGROUND: To date, evidence regarding the effectiveness and safety of individualized controlled ovarian stimulation (COS) compared with standard dose COS has been inadequate. OBJECTIVES: To evaluate the updated evidence from published randomized controlled trials (RCTs) about the efficacy and safety of individualized COS with different ovarian reserve test biomarkers or clinical experience versus standard dose COS. SEARCH STRATEGY: Terms and descriptors related to COS, individualized or standard, and RCT were combined to search, and only English language studies were included. Conference abstracts and comments were excluded. SELECTION CRITERIA: RCTs with comparison between different individualized COS strategies and standard starting dose strategy were included. DATA COLLECTION AND ANALYSIS: Two reviews independently assessed the eligibility of retrieved citations in a predefined standardized manner. Relative risk (RRs) and the weighted mean difference (WMD) with 95% confidence intervals (CIs) were pooled using a random-effects model on R software version 4.2.2. MAIN RESULTS: Compared with the standard dose COS strategy in pairwise meta-analysis, the individualized COS strategy was associated with a notable lower risk of ovarian hyperstimulation syndrome (OHSS; 174/2384 [7.30%] vs 114/2412 [4.73%], RR 0.66, 95% CI: 0.47-0.93, I2 = 46%), a significantly lower risk of hyperresponse to stimulation (hyperresponse; 476/2402 [19.82%] vs 331/2437 [13.58%], RR 0.71, 95% CI: 0.57-0.90, I2 = 61%), and a slightly longer ovarian stimulation days (duration of stimulation; WMD 0.20, 95% CI: 0.01-0.40, I2 = 66%). Bayesian network meta-analysis also found that biomarker-tailored strategy had a significantly lower risk of OHSS than standard dose strategy (OHSS; RR 0.63, 95% CI: 0.41-0.97, I2 = 47.5%). CONCLUSION: Compared with standard dose COS strategy, individualized COS strategy could significantly reduce the risks of OHSS and hyperresponse to stimulation, but the duration of stimulation was slightly longer. TRIAL REGISTRATION: PROSPERO: CRD42023358439.

Enantiospecific Analysis of Carboxylic Acids Using Cinchona Alkaloid Dimers as Chiral Solvating Agents.

Cinchona alkaloid derivatives as Brønsted base catalysts have attracted considerable attention in the field of asymmetric catalysis. However, their potential application as chiral solvating agents has not been described. In this research, we investigated the use of the Cinchona alkaloid dimer, namely, (DHQ)2PHAL, as a chiral solvating agent for discerning various mandelic acid derivatives through 1H NMR spectroscopy. The addition of catalytic amounts of DMAP facilitated this process. Our experimental results demonstrate that dimeric (DHQ)2PHAL exhibits remarkable chiral discrimination properties regarding the diagnostic split protons of 1H NMR signals (including 24 examples, up to 0.321 ppm). Furthermore, it serves as an excellent chiral discriminating agent and provides good resolution for racemic chiral phosphoric acid as determined by 31P NMR spectroscopy. The quality of enantiodifferentiation has also been evaluated by means of the parameter "resolution (Rs)". Significantly, this class of CSAs based on (alkaloid)2linker systems with an azaaromatic linker can be directly employed, which is commercially available in an enantiopure form at very low cost and exhibits promising potential in determining the enantiopurity of α-hydroxy acids by chemoselective and biocatalytic reactions.

Astragaloside IV ameliorates indomethacin-induced intestinal inflammation in rats through inhibiting the activation of NLRP3 inflammasome.

The administration of nonsteroidal anti-inflammatory drugs (NSAIDs) may cause significant intestinal alteration and inflammation and lead to the occurrence of inflammatory diseases resembling duodenal ulcers. Astragaloside IV (AS-IV) is a glycoside of cycloartane-type triterpene isolated from the dried root of Astragalus membranaceus (Fisch.) Bge. (family Fabaceae), and has been used for ameliorating the NSAID-induced inflammation in the small intestine. The present study aimed to investigate the effects of AS-IV on indomethacin (IND)-induced inflammation in the small intestine of rats and its underlying mechanisms. Hematoxylin-eosin (H&E) staining, transmission and scanning electron microscopy were carried out to observe the surface morphology and ultrastructure of the small intestinal mucosa. Immunofluorescence and ELISA tests were employed to detect the expressions of NLRP3, ASC, caspase-1, and NF-κB proteins, as well as inflammatory factors IL-1ß and IL-18, to uncover potential molecular mechanisms responsible for mitigating small intestinal inflammation. The results demonstrated that AS-IV significantly decreased the ulcer index, improved the surface morphology and microstructure of the small intestinal mucosa, and increased mucosal blood flow. Molecular docking revealed a strong and stable binding capacity of AS-IV to NLRP3, ASC, caspase-1, and NF-κB proteins. Further experimental validation exhibited that AS-IV markedly decreased levels of IL-1ß and IL-18, and inhibited the protein expression of NLRP3, ASC, caspase-1, and NF-κB. Our data demonstrate that AS-IV ameliorates IND-induced intestinal inflammation in rats by inhibiting the activation of NLRP3 inflammasome and reducing the release of IL-1ß and IL-18, thereby representing a promising therapy for IND-induced intestinal inflammation.

Six new diterpenoids with anti-inflammatory and cytotoxic activity from Isodon serra.

Diterpenoids occupy an important slot of the natural products diversity space with wide ranges of bioactivities and complex structures, providing potential applications for the development of therapeutics. In this study, we reported four new abietane-type diterpenoids viroxocin B-E (1-4), a new totarane-type diterpenoid viroxocin F (5), and a new sempervirane-type diterpenoid viroxocin G (6) along with four known compounds (7-10), isolated and identified from a widely used Traditional Chinese Medicine, Isodon serra (I. serra). Their structures were established by spectroscopic data analysis, experimental and calculated electronic circular dichroism (ECD) data, as well as X-ray diffraction analysis. Compounds 2, 5, 7, 8 and 10 exhibited promising anti-inflammatory activities in lipopolysaccharide (LPS)-induced RAW 267.4 cells, and their inhibition rates on NO production were more than 60% at 10 µM. Compound 7 showed cytotoxicity against human renal cell carcinoma 769P at 20 µM, the inhibition rate was 52.66%.

Replacing nitrogen in mineral fertilizers with nitrogen in maize straw increases soil water-holding capacity.

Soil water-holding capacity decreases due to long-term mineral fertilizer application. The objective of this study was to determine how replacing mineral fertilizer with maize straw affected the soil water retention curve, soil water content, soil water availability, and soil equivalent pore size. Replacement treatments in which 25% (S25), 50% (S50), 75% (S75), and 100% (S100) of 225 kg ha-1 nitrogen from mineral fertilizer (CK) was replaced with equivalent nitrogen from maize straw were conducted for five years in the Loess Plateau of China. The Gardner model was used to fit the soil water retention curve and calculate the soil water constant and equivalent pore size distribution. The results indicated that the Gardner model fitted well. Replacing nitrogen from mineral fertilizer with nitrogen from straw increased soil specific water capacity, soil readily available water, soil delayed available water, soil available water, soil capillary porosity, and soil available water porosity over time. S25 increased field capacity and wilting point from the fourth fertilization year. S50 enhanced soil readily available water, soil delayed available water, soil available water, and soil available water porosity from the fifth fertilization year, whereas S25 and S75 increased these from the third fertilization year or earlier. Soil specific water capacity, soil readily available water, soil delayed available water, soil available water, soil capillary porosity, and soil available water porosity could better reflect soil water-holding capacity and soil water supply capacity compared with field capacity and wilting point.

Identification of the FGB gene polymorphism and analysis of its association with fat deposition traits in Hu sheep.

As a crucial economic trait, fat deposition is directly related to carcass quality and feed efficiency in sheep. The purpose of this study was to investigate the polymorphisms of the FGB gene related to fat deposition and detect the expression features of the FGB gene in different adipose tissues of sheep by using Sanger sequencing, MassARRAY® SNP technique, and quantitative real-time PCR (qRT-PCR). Results showed that in the intron region of the FGB gene, a SNP g. 3378953 A > T has been identified, and significant association was found between perirenal fat weight, perirenal fat relative weight, mesenteric fat weight, and mesenteric fat relative weight (P < 0.05). Moreover, qRT-PCR analysis showed that FGB was expressed in all three adipose tissues, and FGB gene expression level in the AA genotype was significantly lower than that in the AT or TT genotypes (P < 0.05). Therefore, the FGB gene can be used as a candidate gene to reduce fat deposition in Hu sheep breeding, and the selection of the AA genotype in Hu sheep in production practice is more conducive to improving production efficiency.

Squalene-epoxidase-catalyzed 24(S),25-epoxycholesterol synthesis promotes trained-immunity-mediated antitumor activity.

The importance of trained immunity in antitumor immunity has been increasingly recognized, but the underlying metabolic regulation mechanisms remain incompletely understood. In this study, we find that squalene epoxidase (SQLE), a key enzyme in cholesterol synthesis, is required for ß-glucan-induced trained immunity in macrophages and ensuing antitumor activity. Unexpectedly, the shunt pathway, but not the classical cholesterol synthesis pathway, catalyzed by SQLE, is required for trained immunity induction. Specifically, 24(S),25-epoxycholesterol (24(S),25-EC), the shunt pathway metabolite, activates liver X receptor and increases chromatin accessibility to evoke innate immune memory. Meanwhile, SQLE-induced reactive oxygen species accumulation stabilizes hypoxia-inducible factor 1α protein for metabolic switching into glycolysis. Hence, our findings identify 24(S),25-EC as a key metabolite for trained immunity and provide important insights into how SQLE regulates trained-immunity-mediated antitumor activity.

Protective effect of avicularin against lung cancer via inhibiting inflammation, oxidative stress, and induction of apoptosis: an in vitro and in vivo study.

The purpose of this research was to investigate whether or not avicularin (AVL) possesses any anticancer properties when tested against lung cancer. In the beginning, the effect that it had on the cellular viability of A549 cells was investigated, and it was discovered that AVL has a considerable negative impact on cellular viability. Following that, an investigation using flow cytometry was carried out to investigate its function in the process of apoptosis and the cell cycle of A549 cells. It has been discovered that AVL significantly promotes apoptosis and stops the cell cycle at the G2/M phase. The colony-forming capacity of A549 cells was observed to be greatly suppressed as the AVL concentration increased compared to the group that received no treatment. In addition to this, the benzo(a)pyrene in vivo model was established in order to investigate the pharmacological value of AVL. The findings revealed that AVL greatly prevented the formation of pro-inflammatory cytokines, in addition to the reduction in oxidative stress, which was evidenced by a reduction in the concentration of TNF-α, IL-1ß, IL-6, and MDA with an improvement in the concentration of SOD and GPx, respectively. Our results successfully demonstrated the pharmacological benefit of avicularin against lung cancer, and it has been suggested that it showed a multifactorial effect.

Clinical characteristics and changes in serum CXCL10 and CXCL16 levels in patients with severe mycoplasma pneumonia.

To explore the clinical characteristics and changes in serum CXCL10 and CXCL16 in patients with severe mycoplasma pneumonia, and to analyze the risk factors of severe mycoplasma pneumonia. About 258 children with acute mycoplasma pneumoniae pneumonia (MPP) admitted to the respiratory department of a certain hospital from January 2020 to December 2022 were selected as the study subjects. According to the severity of MPP, patients are divided into 2 groups, namely the mild illness group (Q group) and the severe illness group (Z group). The number of cases in these 2 groups of children is 167 and 91, respectively. The serum CXCL10, CXCL16, and other indicators of 2 groups are tested. Compared to group Q, patients in group Z have a higher proportion of extrapulmonary complications, longer cough time, longer shortness of breath, and longer wheezing time (P < .05). The serum CXCL16 is higher and the proportion of pleural effusion is higher (P < .01). There are more cases of fever, longer fever duration, longer hospital stay, higher serum CXCL10, and higher D-dimer levels (P < .001). The area under the curve of the probability curve for predicting severe mycoplasma pneumonia is 0.975 (P < .05). Children with severe mycoplasma pneumonia have significantly longer fever duration and hospital stay than those with mild symptoms. The serum levels of CXCL10 and CXCL16 are significantly elevated.

Structure-Based Rational and General Strategy for Stabilizing Single-Chain T-Cell Receptors to Enhance Affinity.

The T-cell receptor (TCR) is a crucial molecule in cellular immunity. The single-chain T-cell receptor (scTCR) is a potential format in TCR therapeutics because it eliminates the possibility of αß-TCR mispairing. However, its poor stability and solubility impede the in vitro study and manufacturing of therapeutic applications. In this study, some conserved structural motifs are identified in variable domains regardless of germlines and species. Theoretical analysis helps to identify those unfavored factors and leads to a general strategy for stabilizing scTCRs by substituting residues at exact IMGT positions with beneficial propensities on the consensus sequence of germlines. Several representative scTCRs are displayed to achieve stability optimization and retain comparable binding affinities with the corresponding αß-TCRs in the range of µM to pM. These results demonstrate that our strategies for scTCR engineering are capable of providing the affinity-enhanced and specificity-retained format, which are of great value in facilitating the development of TCR-related therapeutics.

Expansion and transmission dynamics of high risk carbapenem-resistant Klebsiella pneumoniae subclones in China: An epidemiological, spatial, genomic analysis.

AIMS: Carbapenem-resistant Klebsiella pneumonia (CRKP) is a global threat that varies by region. The global distribution, evolution, and clinical implications of the ST11 CRKP clone remain obscure. METHODS: We conducted a multicenter molecular epidemiological survey using isolates obtained from 28 provinces and municipalities across China between 2011 and 2021. We integrated sequences from public databases and performed genetic epidemiology analysis of ST11 CRKP. RESULTS: Among ST11 CRKP, KL64 serotypes exhibited considerable expansion, increasing from 1.54% to 46.08% between 2011 and 2021. Combining our data with public databases, the phylogenetic and phylogeography analyses indicated that ST11 CRKP appeared in the Americas in 1996 and spread worldwide, with key clones progressing from China's southeastern coast to the inland by 2010. Global phylogenetic analysis showed that ST11 KL64 CRKP has evolved to a virulent, resistant clade with notable regional spread. Single-nucleotide polymorphism (SNP) analysis identified BMPPS (bmr3, mltC, pyrB, ppsC, and sdaC) as a key marker for this clade. The BMPPS SNP clade is associated with high mortality and has strong anti-phagocytic and competitive traits in vitro. CONCLUSIONS: The high-risk ST11 KL64 CRKP subclone showed strong expansion potential and survival advantages, probably owing to genetic factors.

Clinical characteristics of acute non-varicose upper gastrointestinal bleeding and the effect of endoscopic hemostasis.

BACKGROUND: Acute non-variceal upper gastrointestinal bleeding (ANVUGIB) constitutes a prevalent emergency within Gastroenterology, encompassing 80%-90% of all gastrointestinal hemorrhage incidents. This condition is distinguished by its abrupt onset, swift progression, and notably elevated mortality rate. AIM: To gather clinical data from patients with ANVUGIB at our hospital in order to elucidate the clinical characteristics specific to our institution and analyze the therapeutic effectiveness of endoscopic hemostasis. METHODS: We retrospectively retrieved the records of 532 patients diagnosed with ANVUGIB by endoscopy at our hospital between March 2021 and March 2023, utilizing our medical record system. Data pertaining to general patient information, etiological factors, disease outcomes, and other relevant variables were meticulously collected and analyzed. RESULTS: Among the 532 patients diagnosed with ANVUGIB, the male-to-female ratio was 2.91:1, with a higher prevalence among males. Notably, 43.6% of patients presented with black stool as their primary complaint, while 27.4% had hematemesis as their initial symptom. Upon admission, 17% of patients exhibited both hematemesis and black stool, while most ANVUGIB patients primarily complained of overt gastrointestinal bleeding. Urgent routine blood examinations at admission revealed that 75.8% of patients had anemia, with 63.4% experiencing moderate to severe anemia, and 1.5% having extremely severe anemia (hemoglobin < 30 g/L). With regard to etiology, 53.2% of patients experienced bleeding without a definitive trigger, 24.2% had a history of using gastric mucosa-irritating medications, 24.2% developed bleeding after alcohol consumption, 2.8% attributed it to improper diet, 1.7% to emotional excitement, and 2.3% to fatigue preceding the bleeding episode. Drug-induced ANVUGIB was more prevalent in the elderly than middle-aged and young individuals, while bleeding due to alcohol consumption showed the opposite trend. Additionally, diet-related bleeding was more common among the young age group compared to the middle-aged group. Gastrointestinal endoscopy identified peptic ulcers as the most frequent cause of ANVUGIB (73.3%), followed by gastrointestinal malignancies (10.9%), acute gastric mucous lesions (9.8%), and androgenic upper gastrointestinal bleeding (1.5%) among inpatients with ANVUGIB. Of the 532 patients with gastrointestinal bleeding, 68 underwent endoscopic hemostasis, resulting in an endoscopic treatment rate of 12.8%, with a high immediate hemostasis success rate of 94.1%. CONCLUSION: ANVUGIB patients exhibit diverse characteristics across different age groups, and endoscopic hemostatic treatments have demonstrated remarkable efficacy.

Daily feeding frequency affects feed intake and body weight management of growing layers.

The objective of this study was to investigate the effect of feeding behavior on feed intake and body weight in growing layers and the underlying mechanisms, thereby providing a scientific foundation for optimal feeding practices in growing layers' management. A total of 144 Hy-line brown growing layers of 10 wk old and similar body weight, were divided into 3 treatment groups with different feeding frequency and equal cumulative daily feeding amount: the once-a-day feeding group (F1) was fed at 9:00 am every day, with feeding amount of 150 g/layer; the twice-a-day feeding group (F2) were fed at 9:00 am and 13:00 pm every day, with each feeding amount of 75 g/layer; the 4 times-a-day feeding group (F4) were fed at 9:00 am, 11:00 am, 13:00 pm, and 15:00 pm every day, with each feeding amount of 37.5 g/layer. Pre-experiment lasted for 1 wk and formal experiment lasted for 8 wk. The results indicated that the daily feed intake and body weight were decreased (P < 0.05) while feed conversion ratio was not affected (P > 0.05) as daily feeding times increased. The glandular stomach proportion was significantly increased in twice-a-day feeding group, while liver proportion and ileum length were significantly increased in 4 times-feeding group (P < 0.05). Additionally, 4 times-feeding daily resulted in a significant elevation of blood glucose levels, which may have suppressed feed intake (P < 0.05). In 4 times-feeding group, the plasma triglyceride levels increased as feeding times, accompanied by a notable up-regulation in the mRNA level of appetite-suppressing gene, hypothalamic pro-opiomelanocortin (POMC) and glandular stomach ghrelin. This modulation effectively suppressed the subsequent feed intake and body weight. Therefore, 4 times feeding daily is recommended in growing layers' management, because it reduced the feed cost without affecting the feed conversion efficiency.

Association between Body Mass Index and Medication-Overuse Headache among Individuals with Migraine: A Cross-Sectional Study.

INTRODUCTION: Medication-overuse headache (MOH) is a secondary chronic headache disorder that occurs in individuals with a pre-existing primary headache disorder, particularly migraine disorder. Obesity is often combined with chronic daily headaches and is considered a risk factor for the transformation of episodic headaches into chronic headaches. However, the association between obesity and MOH among individuals with migraine has rarely been studied. The present study explored the association between body mass index (BMI) and MOH in people living with migraine. METHODS: This cross-sectional study is a secondary analysis of data from the Survey of Fibromyalgia Comorbidity with Headache study. Migraine and MOH were diagnosed using the criteria of the International Classification of Headache Disorders, 3rd Edition. BMI (kg/m2) is calculated by dividing the weight (kg) by the square of the height (m). Multivariable logistic regression analysis was used to evaluate the association between BMI and MOH. RESULTS: A total of 2,251 individuals with migraine were included, of whom 8.7% (195/2,251) had a concomitant MOH. Multivariable logistic regression analysis, adjusted for age, sex, education level, headache duration, pain intensity, headache family history, chronic migraine, depression, anxiety, insomnia, and fibromyalgia, demonstrated there was an association between BMI (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.11; p = 0.031) and MOH. The results remained when the BMI was transformed into a category. Compared to individuals with Q2 (18.5 kg/m2 ≤ BMI ≤23.9 kg/m2), those with Q4 (BMI ≥28 kg/m2) had an adjusted OR for MOH of 1.81 (95% CI, 1.04-3.17; p = 0.037). In the subgroup analyses, BMI was associated with MOH among aged more than 50 years (OR, 1.13; 95%, 1.03-1.24), less than high school (OR, 1.08; 95%, 1.01-1.15), without depression (OR, 1.06; 95%, 1.01-1.12), and without anxiety (OR, 1.06; 95%, 1.01-1.12). An association between BMI and MOH was found in a sensitivity analysis that BMI was classified into four categories according to the World Health Organization guidelines. CONCLUSION: In this cross-sectional study, BMI was associated with MOH in Chinese individuals with migraine.