Uncovering Language Disparity of ChatGPT on Retinal Vascular Disease Classification: Cross-Sectional Study.

BACKGROUND: Benefiting from rich knowledge and the exceptional ability to understand text, large language models like ChatGPT have shown great potential in English clinical environments. However, the performance of ChatGPT in non-English clinical settings, as well as its reasoning, have not been explored in depth. OBJECTIVE: This study aimed to evaluate ChatGPT's diagnostic performance and inference abilities for retinal vascular diseases in a non-English clinical environment. METHODS: In this cross-sectional study, we collected 1226 fundus fluorescein angiography reports and corresponding diagnoses written in Chinese and tested ChatGPT with 4 prompting strategies (direct diagnosis or diagnosis with a step-by-step reasoning process and in Chinese or English). RESULTS: Compared with ChatGPT using Chinese prompts for direct diagnosis that achieved an F1-score of 70.47%, ChatGPT using English prompts for direct diagnosis achieved the best diagnostic performance (80.05%), which was inferior to ophthalmologists (89.35%) but close to ophthalmologist interns (82.69%). As for its inference abilities, although ChatGPT can derive a reasoning process with a low error rate (0.4 per report) for both Chinese and English prompts, ophthalmologists identified that the latter brought more reasoning steps with less incompleteness (44.31%), misinformation (1.96%), and hallucinations (0.59%) (all P<.001). Also, analysis of the robustness of ChatGPT with different language prompts indicated significant differences in the recall (P=.03) and F1-score (P=.04) between Chinese and English prompts. In short, when prompted in English, ChatGPT exhibited enhanced diagnostic and inference capabilities for retinal vascular disease classification based on Chinese fundus fluorescein angiography reports. CONCLUSIONS: ChatGPT can serve as a helpful medical assistant to provide diagnosis in non-English clinical environments, but there are still performance gaps, language disparities, and errors compared to professionals, which demonstrate the potential limitations and the need to continually explore more robust large language models in ophthalmology practice.

The reference value of anti-Müllerian hormone to diagnose polycystic ovary syndrome is inversely associated with BMI: a retrospective study.

BACKGROUND: This study aimed to evaluate the cut-off value of anti-Müllerian hormone (AMH) combined with body mass index (BMI) in the diagnosis of polycystic ovary syndrome (PCOS) and polycystic ovary morphology (PCOM). METHODS: This retrospective study included 15,970 patients: 3775 women with PCOS, 2879 women with PCOM, and 9316 patients as controls. Multivariate logistic regression analysis was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for AMH. We randomly divided the patients into two data sets. In dataset 1, a receiver operating characteristic (ROC) curve was generated to analyze the accuracy of basic AMH levels in diagnosing PCOS and PCOM. The optimal cut-off value was calculated in dataset 1 and validated in dataset 2, expressed as sensitivity and specificity. RESULTS: In the PCOS group, obese patients had the lowest AMH levels, while underweight patients had the highest AMH level (P < 0.001). After adjusting for age, the ratio of luteinizing hormone (LH) and follicle stimulating hormone (FSH), serum testosterone level, and BMI, AMH was an independent predictor of PCOS and PCOM. In the group with BMI < 18.5 kg/m2, the optimistic AMH cut-off value was 5.145 ng/mL with a sensitivity of 84.3% and specificity of 89.1%, whereas in the BMI ≥ 28 kg/m2 group, the optimistic AMH cut-off value was 3.165 ng/mL with a sensitivity of 88.7% and specificity of 74.6%. For the BMI range categories of 18.5-24, 24.0-28 kg/m2, the optimistic AMH cut-off values were 4.345 ng/mL and 4.115 ng/mL, respectively. The tendency that the group with lower weight corresponded to higher AMH cut-off values was also applicable to PCOM. In the same BMI category, patients with PCOM had a lower AMH diagnosis threshold than those with PCOS (< 18.5 kg/m2, 5.145 vs. 4.3 ng/mL; 18.5-24 kg/m2, 4.345 vs. 3.635 ng/mL; 24.0-28 kg/m2, 4.115 vs. 3.73 ng/mL; ≥ 28 kg /m2, 3.165 vs. 3.155 ng/mL). These cut-off values had a good diagnostic efficacy in the validation dataset. Based on different phenotypes and severity of ovulation disorders, the distribution of AMH in PCOS were also significantly different (P < 0.001). CONCLUSIONS: AMH is a potential diagnostic indicator of PCOS and is adversely associated with BMI. The AMH cut-off value for diagnosing PCOS was significantly higher than that for PCOM.

4R Tau Modulates Cocaine-Associated Memory through Adult Dorsal Hippocampal Neurogenesis.

The development, persistence and relapse of drug addiction require drug memory that generally develops with drug administration-paired contextual stimuli. Adult hippocampal neurogenesis (AHN) contributes to cocaine memory formation; however, the underlying mechanism remains unclear. Male mice hippocampal expression of Tau was significantly decreased during the cocaine-associated memory formation. Genetic overexpression of four microtubule-binding repeats Tau (4R Tau) in the mice hippocampus disrupted cocaine memory by suppressing AHN. Furthermore, 4R Tau directly interacted with phosphoinositide 3-kinase (PI3K)-p85 and impaired its nuclear translocation and PI3K-AKT signaling, processes required for hippocampal neuron proliferation. Collectively, 4R Tau modulates cocaine memory formation by disrupting AHN, suggesting a novel mechanism underlying cocaine memory formation and provide a new strategy for the treatment of cocaine addiction.SIGNIFICANCE STATEMENT Drug memory that generally develops with drug-paired contextual stimuli and drug administration is critical for the development, persistence and relapse of drug addiction. Previous studies have suggested that adult hippocampal neurogenesis (AHN) plays a role in cocaine memory formation. Here, we showed that Tau was significantly downregulated in the hippocampus in the cocaine memory formation. Tau knock-out (KO) promoted AHN in the hippocampal dentate gyrus (DG), resulting in the enhanced memory formation evoked by cocaine-cue stimuli. In contrast, genetically overexpressed 4R Tau in the hippocampus disrupted cocaine-cue memory by suppressing AHN. In addition, 4R Tau interacted directly with phosphoinositide 3-kinase (PI3K)-p85 and hindered its nuclear translocation, eventually repressing PI3K-AKT signaling, which is essential for hippocampal neuronal proliferation.

Structure elucidation, biogenesis, and bioactivities of acylphloroglucinol-derived meroterpenoid enantiomers from Dryopteris crassirhizoma.

Twenty-four racemic acylphloroglucinol meroterpenoids including eighteen unusual stuctures (3 âˆ¼ 10, 13, 14, and 17 âˆ¼ 24), and a major component filixic acid ABA (25), were isolated from Dryopteris crassirhizoma. Structurally, the dimeric acylphloroglucinol derivatives possess unprecedented skeletons of mixed acylphloroglucinol and sesquiterpene biosynthetic origin. The stereochemistries of six reported meroterpenoids with undefined chiral centers were reassigned. Two intriguing methods by analyzing a) the regularity of chemical shift variation of protons and carbons around the stereogenic centers, and b) pyridine-induced deshielding effect of hydroxy groups, to discriminate relative configurations of flexible long-chain alcohol with chiral centers separated by three or seven covalent bonds, were successfully applied. A non-enzymatic biosynthesis of 1 âˆ¼ 24 was assumed based on a rare single-crystal cluster formed with two diastereomeric enantiomer pairs (±1/±2) and chiral HPLC analyses. Meroterpenoids 13 and 14 showed obvious inhibitory effects on NO production in LPS-induced RAW264.7, and suppressed the expression of iNOS, COX-2, IL-1ß, and IL-18. Their anti-inflammatory activity was closely related to the inhibition of the formation and function of inflammasomes. Additionally, the known 25 showed antiviral efficacy against the influenza viruse A/Puerto Rico/8/1934 (H1N1).

A nonlinear association between body roundness index and all-cause mortality and cardiovascular mortality in general population.

OBJECTIVE: The aim of the study was to investigate the association between body roundness index (BRI) and all-cause mortality and cardiovascular mortality in general population. DESIGN: A retrospective cohort study. SETTING: The status of cardiovascular mortality and all-cause mortality of participants were followed through 31 December 2015. Multivariate adjusted Cox restricted cubic spline regression models and Kaplan-Meier survival curves were used to evaluate the relationship between BRI and cardiovascular mortality and all-cause mortality. PARTICIPANTS: A sample of 47 356 participants from the National Health and Nutrition Examination Surveys 1999-2014 with aged ≥18 years. RESULTS: Mean age was 47 years and female were 49·9 %. During a median follow-up of 92 months, 4715 participants died from any cause, with 985 died of CVD. In multivariate adjusted Cox regression, compared with the lowest quartile of Body roundness index (BRI), the hazard ratios (HR) for all-cause mortality from other quartiles were 0·83, 95 % CI (0·75, 0·92), 0·73, 95 % CI (0·65, 0·81) and 0·80, 95 % CI (0·72, 0·89), respectively (Pfor trend < 0·05) and the HR for cardiovascular mortality from other quartiles were 0·79, 95 % CI (0·62, 1·00), 0·78, 95 % CI (0·62, 0·99) and 0·79, 95 % CI (0·62, 1·01), respectively (P for trend > 0·05). In the restricted cubic spline regression models, the relationship was showed U-shaped between BRI and all-cause mortality and cardiovascular mortality. In Kaplan-Meier survival curves, the lowest cumulative survival rate of cardiovascular mortality and all-cause mortality was recorded in the highest BRI quartile. CONCLUSIONS: The U-shaped association between BRI and all-cause mortality and cardiovascular mortality in a large population-based cohort was observed.

The association of blood lipid parameters variability with ischemic stroke in hypertensive patients.

BACKGROUND AND AIMS: The relationship between lipid variability and stroke among patients with hypertension were inconclusive. We aimed to investigate the association of lipid variability with ischemic stroke in hypertensive patients. METHODS AND RESULTS: This retrospective cohort study included 4995 individuals with hypertension between 2013 and 2015, and recorded their status of ischemic stroke until the end of 2018. The variability in total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured using the standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM) and average absolute difference between successive values (ASV). Multivariate Cox proportional hazards models with hazard ratios (HRs) and 95% confidence interval (CI) were performed. There were 110 cases of ischemic stroke during a median follow up of 4.2 years. The multivariable adjusted HRs and 95% CIs comparing the highest versus the lowest quartiles of SD of TC, LDL-C, HDL-C and TG were 4.429 (95% CI: 2.292, 8.560), 2.140 (95% CI: 1.264, 3.621), 1.368 (95% CI: 0.793, 2.359) and 1.421 (95% CI: 0.800, 2.525), respectively. High variability in TC and LDL-C were associated with a higher risk for ischemic stroke. Similarly, the results were consistent when calculating variability of TC and LDL-C using CV, ASV and VIM, and in various subgroup analyses. CONCLUSION: Higher variability of TC and LDL-C associated with the risk of ischemic stroke among hypertensive patients. These findings suggest reducing variability of lipid parameters may decrease adverse outcomes.

[Chemical constituents of Psidium guajava and their antitumor and antifungal activities].

Twenty-six compounds, including sixteen meroterpenoids(1-16), a triterpenoid(17), four terpenoid derivatives(18-21), and five aromatic compounds(22-26), were isolated from the leaves of Psidium guajava. Their structures were identified by spectroscopic analyses including NMR and MS. Compounds 21-26 were obtained from plants of Psidium for the first time. Based on the structure,(R)-2-ethylhexyl 2H-1,2,3-triazole-4-carboxylate(24 a), an α-glucosidase inhibitor recently isolated from Paramignya trimera, should be revised as compound 24. Meroterpenoids 1-16 were evaluated for their antitumor and antifungal activities. Meroterpenoids psiguajadial D(4), guapsidial A(5), 4,5-diepipsidial A(7), guadial A(14), and guadial B(15) showed cytotoxicities against five human tumor cell lines(HL-60, A-549, SMMC-7721, MCF-7, and SW-480), among which 5 was the most effective with an IC_(50) of 3.21-9.94 µmol·L~(-1).

Design and biological evaluation of tetrahydropyridine derivatives as novel human GPR119 agonists.

A series of novel tetrahydropyridine derivatives were prepared and evaluated using cell-based measurements. Systematic optimization of general structure G-1 led to the identification of compound 35 (EC50 = 4.9 nM) and 37 (EC50 = 8.8 nM) with high GPR119 agonism activity and moderate clog P. Through single and long-term pharmacodynamic experiments, we found that compound35 showed a hypoglycemic effect and may have an effect on improving basal metabolic rate in DIO mice. Both in vitro and in vivo tests indicated that compound 35 was a potential potent GPR119 agonist in allusion to T2DM treatment.

Targeted delivery of mitochondria to the liver in rats.

BACKGROUND AND AIM: Mitochondrial damage is commonly involved in liver injury. We have previously shown that normal mitochondria can be coated with a carrier protein to form complexes that are specifically taken up by liver cells in culture. The aim of the current study was to determine whether mitochondrial complexes could be specifically delivered to the livers of living rats by intravenous injection. METHODS: Mitochondria were harvested from fresh mouse liver, mixed with an asialoglycoprotein-based carrier, asialoorosomucoid-polylysine (AsOR-PL), and purified to form complexes. To facilitate the release of internalized mitochondria from endosomes, an endosomolytic peptide, listeriolysin O (LLO), was coupled to AsOR to form AsOR-LLO. Mitochondria alone, mitochondrial complexes with AsOR-PL, and mitochondrial complexes plus AsOR-LLO conjugate all containing the same number of mitochondria were injected intravenously. Animals were killed, and organs were removed and analyzed by quantitative polymerase chain reaction of mouse mitochondrial DNA, electron microscopy (EM), and in situ polymerase chain reaction and hybridization followed by immunohistochemical analyses. RESULTS: Calculations revealed that approximately 27% of the total injected mitochondria was detected in the liver, while less than 2% was found in spleen, and < 1% in lungs. Immunohistochemistry showed that mouse mitochondrial DNA staining was minimal with mitochondrial complexes alone, strong periportal with mitochondrial complexes co-injected with AsOR-LLO, and absent with mitochondria alone. CONCLUSIONS: Targetable mitochondrial complexes can be delivered to rat liver, and the efficiency of that process is greatly enhanced by co-injection of a targetable endosomal release agent, AsOR-LLO.

A dose-independent association of triglyceride levels with all-cause mortality among adults population.

BACKGROUND: The relationship between triglyceride (TG) level and the mortality risk of all-cause and cardiovascular disease is not entirely consistent among adults. METHODS: The present analysis included adult participants from National Health and Nutrition Examination Surveys (NHANES) between the periods 1999-2014. The levels of TG were categorized into < 150, 150-199, 200-250 and ≥ 250 mg/dL respectively. Multivariate Cox regression analysis, stratified analysis and generalized additive model were conducted to reveal the correlation between TG and mortality risk. Results were presented in hazard ratio (HRs) and 95% confidence intervals (CIs). RESULTS: There were 18,781 (9130 males, mean age was 45.64 years) participants being included in the analysis. The average follow-up period was 8.25 years, where 1992 (10.61%) cases of all-cause and 421 (2.24%) cardiovascular death have occurred. In the multivariate Cox model, every 1 mg/dL raise in TG has significantly associated with all-cause mortality (HR: 1.08, 95% CI: 1.02, 1.15) but not cardiovascular mortality (HR: 1.10, 95% CI: 0.97, 1.24). When using TG <  150 mg/dL as reference, TG ≥ 250 mg/dL associated with death from all-cause (HR = 1.34, 95% CI: 1.12, 1.60; P = 0.0016 but not cardiovascular death (HR = 1.26, 95% CI: 0.85, 1.88; P = 0.2517). According to smoothing spline plots, the risk of all-cause was the lowest when TG was approximately 135 mg/dL. CONCLUSION: TG might have a dose-independent association with all-cause mortality among adults in United States.

WITHDRAWN: The role of TNFα in promoting hepatic MRP4 expression via the p38-Rb-E2F1 pathway in human obstructive cholestasis.

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Serum Cytokines Th1, Th2, and Th17 Expression Profiling in Active Lupus Nephritis-IV: From a Southern Chinese Han Population.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by aberrant T cell immune response. Diffuse proliferative lupus nephritis (LN-IV) is the most common, severe, and active form of lupus nephritis. In this study, we investigated the production of Th1, Th2, and Th17 cytokines in prediction of active form of LN-IV. ProcartaPlex multiplex immunoassays panels were used for detection of serum Th1, Th2, and Th17 cytokines profiling. Th1 and Th17 cytokines (IL-18, IFN-γ, IL-12p70, IL-6, and IL-17A) were considerably expressed in the serum of lupus nephritis IV patients in comparison to the healthy control. However, only IL18 and IL6 were higher in class IV versus class III lupus nephritis. Importantly, the ratios of Th1/Th2 (IL-18/IL-4) and Th17/Th2 (IL-17A/IL-4) were significantly elevated in LN-IV when compared with LN-III, LN-V, and healthy controls. Consistently, the serum cytokines IL-18, IL-17A, and IFN-γ were markedly expressed in LN-IV patient glomeruli and interstitial tissue compared to other classes of LN by IHC. ROC further suggests that IL-18 was a potential marker for LN-IV. The data from our study suggests that the early detection and quantification of these cytokines may help in prediction of active form of LN-IV.

Canalicular membrane MRP2/ABCC2 internalization is determined by Ezrin Thr567 phosphorylation in human obstructive cholestasis.

BACKGROUND & AIMS: Multidrug resistance-associated protein 2 (MRP2) excretes conjugated organic anions including bilirubin and bile acids. Malfunction of MRP2 leads to jaundice in patients. Studies in rodents indicate that Radixin plays a critical role in determining Mrp2 canalicular membrane expression. However, it is not known how human hepatic MRP2 expression is regulated in cholestasis. METHODS: We assessed liver MRP2 expression in patients with obstructive cholestasis caused by gallstone blockage of bile ducts, and investigated the regulatory mechanism in HepG2 cells. RESULTS: Western blot detected that liver MRP2 protein expression in obstructive cholestatic patients (n=30) was significantly reduced to 25% of the non-cholestatic controls (n=23). Immunoprecipitation identified Ezrin but not Radixin associating with MRP2 in human livers, and the increased amount of phospho-Ezrin Thr567 was positively correlated with the amount of co-precipitated MRP2 in cholestatic livers, whereas Ezrin and Radixin total protein levels were unchanged in cholestasis. Further detailed studies indicate that Ezrin Thr567 phosphorylation plays an important role in MRP2 internalization in HepG2 cells. Since increased expression of PKCα, δ and ε were detected in these cholestatic livers, we further confirmed that these PKCs stimulated Ezrin phosphorylation and reduced MRP2 membrane expression in HepG2 cells. Finally, we identified GP78 as the key ubiquitin ligase E3 involved in MRP2 proteasome degradation. CONCLUSIONS: Activation of liver PKCs during cholestasis leads to Ezrin Thr567 phosphorylation resulting in MRP2 internalization and degradation where ubiquitin ligase E3 GP78 is involved. This process provides a mechanistic explanation for jaundice seen in patients with obstructive cholestasis.

Expression and significance of pigment epithelium-derived factor and vascular endothelial growth factor in colorectal adenoma and cancer.

BACKGROUND: The incidence and mortality of colorectal cancer (CRC) are among the highest in the world, and its occurrence and development are closely related to tumor neovascularization. When the balance between pigment epithelium-derived factors (PEDF) that inhibit angiogenesis and vascular endothelial growth factors (VEGF) that stimulate angiogenesis is broken, angiogenesis is out of control, resulting in tumor development. Therefore, it is very necessary to find more therapeutic targets for CRC for early intervention and later treatment. AIM: To investigate the expression and significance of PEDF, VEGF, and CD31-stained microvessel density values (CD31-MVD) in normal colorectal mucosa, adenoma, and CRC. METHODS: In this case-control study, we collected archived wax blocks of specimens from the Digestive Endoscopy Center and the General Surgery Department of Chengdu Second People's Hospital from April 2022 to October 2022. Fifty cases of specimen wax blocks were selected as normal intestinal mucosa confirmed by electronic colonoscopy and concurrent biopsy (normal control group), 50 cases of specimen wax blocks were selected as colorectal adenoma confirmed by electronic colonoscopy and pathological biopsy (adenoma group), and 50 cases of specimen wax blocks were selected as CRC confirmed by postoperative pathological biopsy after inpatient operation of general surgery (CRC group). An immunohistochemical staining experiment was carried out to detect PEDF and VEGF expression in three groups of specimens, analyze their differences, study the relationship between the two and clinicopathological factors in CRC group, record CD31-MVD in the three groups, and analyze the correlation of PEDF, VEGF, and CD31-MVD in the colorectal adenoma group and the CRC group. The F test or adjusted F test is used to analyze measurement data statistically. Kruskal-Wallis rank sum test was used between groups for ranked data. The chi-square test, adjusted chi-square test, or Fisher's exact test were used to compare the rates between groups. All differences between groups were compared using the Bonferroni method for multiple comparisons. Spearman correlation analysis was used to test the correlation of the data. The test level (α) was 0.05, and a two-sided P< 0.05 was considered statistically significant. RESULTS: The positive expression rate and expression intensity of PEDF were gradually decreased in the normal control group, adenoma group, and CRC group (100% vs 78% vs 50%, χ2 = 34.430, P < 0.001; ++~++ vs +~++ vs -~+, H = 94.059, P < 0.001), while VEGF increased gradually (0% vs 68% vs 96%, χ2 = 98.35, P < 0.001; - vs -~+ vs ++~+++, H = 107.734, P < 0.001). In the CRC group, the positive expression rate of PEDF decreased with the increase of differentiation degree, invasion depth, lymph node metastasis, distant metastasis, and TNM stage (χ2 = 20.513, 4.160, 5.128, 6.349, 5.128, P < 0.05); the high expression rate of VEGF was the opposite (χ2 = 10.317, 13.134, 17.643, 21.844, 17.643, P < 0.05). In the colorectal adenoma group, the expression intensity of PEDF correlated negatively with CD31-MVD (r = -0.601, P < 0.001), whereas VEGF was not significantly different (r = 0.258, P = 0.07). In the CRC group, the expression intensity of PEDF correlated negatively with the expression intensity of CD31-MVD and VEGF (r = -0.297, P < 0.05; r = -0.548, P < 0.05), while VEGF expression intensity was positively related to CD31-MVD (r = 0.421, P = 0.002). CONCLUSION: It is possible that PEDF can be used as a new treatment and prevention target for CRC by upregulating the expression of PEDF while inhibiting the expression of VEGF.

LncRNA MFRL regulates the phenotypic switch of vascular smooth muscle cells to attenuate arterial remodeling by encoding a novel micropeptide MFRLP.

BACKGROUND: Arterial remodeling is a common pathophysiological change in the pathogenesis of cardiovascular diseases in which the phenotypic switch of vascular smooth muscle cells (VSMC) plays an important role. Recently, an increasing number of long non-coding RNAs(lncRNAs) have been shown to encode micropeptides that play biological roles and have great clinical transformation potential. However, the role of micropeptides encoded by lncRNAs in arterial remodeling has not been well studied and requires further exploration. METHODS AND RESULTS: Through bioinformatic analysis and experimental verification, we found that a new lncRNA, the mitochondrial function-related lncRNA (MFRL), encodes a 64-amino acid micropeptide, MFRLP. MFRL and MFRLP play important roles in the phenotypic switch of VSMC. Further experiments showed that MFRLP interacts with mitochondrial cytochrome b to reduce accumulation of reactive oxygen species, suppress mitophagy and inhibit the VSMC switch from contractile to synthetic phenotype. CONCLUSIONS: LncRNA MFRL encodes the micropeptide MFRLP, which interacts with mitochondrial cytochrome b to inhibit the VSMC switch from contractile to synthetic phenotype and improve arterial remodeling.

Mouse KL2 is a unique MTSE involved in chromosome-based spindle organization and regulated by multiple kinases during female meiosis.

Microtubule-severing enzymes (MTSEs) play important roles in mitosis and meiosis of the primitive organisms. However, no studies have assessed their roles in mammalian meiosis of females, whose abnormality accounts for over 80% of the cases of gamete-originated human reproductive disease. In the current study, we reported that katanin-like 2 (KL2) was the only MTSE concentrating at chromosomes. Furthermore, the knockdown of KL2 significantly reduced chromosome-based increase in the microtubule (MT) polymer, increased aberrant kinetochore-MT (K-MT) attachment, delayed meiosis, and severely affected normal fertility. Importantly, we demonstrated that the inhibition of aurora B, a key kinase for correcting aberrant K-MT attachment, eliminated KL2 from chromosomes completely. KL2 also interacted with phosphorylated eukaryotic elongation factor-2 kinase; they competed for chromosome binding. We also observed that the phosphorylated KL2 was localized at spindle poles, and that KL2 phosphorylation was regulated by extracellular signal-regulated kinase 1/2. In summary, our study reveals a novel function of MTSEs in mammalian female meiosis and demonstrates that multiple kinases coordinate to regulate the levels of KL2 at chromosomes.

Association between the stress-hyperglycemia ratio and all-cause mortality in community-dwelling populations: An analysis of the National Health and Nutrition Examination Survey (NHANES) 1999-2014.

BACKGROUND: Reportedly, the stress-hyperglycemia ratio (SHR) is closely associated with poor prognosis in patients with severe acute disease. However, the community-dwelling may also be in a state of stress due to environmental exposure. Our study aimed to explore the association between SHR and all-cause mortality in the community-dwelling population. METHODS: A total of 18 480 participants were included out of 82 091 from the NHANES 1999-2014 survey. The Kaplan-Meier survival analyses were used to assess the disparities in survival rates based on SHR, and the log-rank test was employed to investigate the distinctions between groups. The multivariate Cox regression analysis and restricted cubic spline (RCS) analysis were performed to assess the association of SHR with all-cause mortality. A subgroup analysis was also conducted. RESULTS: A total of 3188 deaths occurred during a median follow-up period of 11.0 (7.7; 15.4) years. The highest risk for all-cause mortality was observed when SHR≤ 0.843 or SHR ≥0.986 (log-rank p < .001). After adjusting for the confounding factors, compared with subjects in the second SHR quartile (Q2), participants in the highest (Q4, adjusted hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.28-1.73) and lowest quartiles (Q1, adjusted HR 1.37, 95% CI 1.16-1.60) have a higher probability of all-cause death. The RCS observed a dose-response U-shaped association between SHR and all-cause mortality. The U-shaped association between SHR and all-cause mortality was similar across subgroup analysis. CONCLUSIONS: The SHR was significantly associated with all-cause mortality in the community-dwelling population, and the relationship was U-shaped.

Sustained efficacy of adefovir add-on therapy in chronic hepatitis B patient with a poor virological response to peginterferon alfa.

BACKGROUND: Currently, there is no consensus on the recommendation of peginterferon alfa (pegIFNα) to chronic hepatitis B (CHB) patients with poor viral response (EVR). This study aimed to assess the sustained curative efficacy of adefovir (ADV) add-on therapy in optimizing pegIFNα monotherapy. METHODS: A total of 85 hepatitis B e antigen (HBeAg)-positive CHB patients with poor virological response at month 6 after starting pegIFNα-2a were enrolled, and received either pegIFNα-2a continuing monotherapy (group A, n = 51) or add-on therapy with ADV (group B, n = 34). The treatment duration for all patients was 6 months, and the sustained responses after the end of treatment were evaluated between two groups. RESULTS: The baseline characteristics were comparable between two groups. At months 6 after treatment completion, the sustained virological response (SVR) rates were 31.4% and 73.5%, the sustained biochemical response (SBR) rates were 39.2% and 85.3% in group A and group B respectively, and the difference in either SVR or SBR was statistically significant (both p < 0.001). As compared to patients in group A, significantly more patients in group B obtained HBeAg loss (19.6% vs. 55.9%, p = 0.001) and seroconversion (13.7% vs. 41.2%, p = 0.004). CONCLUSION: ADV add-on therapy could significantly improve and sustain the curative efficacy of CHB patient with poor virological response to pegIFNα-2a monotherapy, but further large well-designed randomized controlled trials are needed to confirm our findings.

Higher Sensitivity to Thyroid Hormones May Be Linked to Maintaining the Healthy Metabolic Condition in People with Obesity: New Insight from NHANES.

INTRODUCTION: Obesity contributes to the pathogenesis of diverse metabolic diseases, yet the mechanism underlying metabolically healthy obesity (MHO) remains elusive. Thyroid hormones and sensitivity to them have a major impact on metabolism. Our study aimed to investigate the association between MHO and thyroid hormone sensitivity. METHODS: Thyroid hormone indices, including the thyroid-stimulating hormone (TSH) index (TSHI), the Thyrotroph Thyroxine Sensitivity Index (TTSI), the Thyroid Feedback Quantile-Based Index (TFQI), and the Parametric Thyroid Feedback Quantile-Based Index (PTFQI), were calculated based on a non-institutionalized US sample in the National Health and Nutrition Examination Survey (NHANES, 2007-2012). Participants were divided into four groups (metabolically healthy non-obesity [MHNO], metabolically unhealthy non-obesity [MUNO], MHO, and metabolically unhealthy obesity [MUO]) according to their body mass index and metabolic profiles. Linear regression, logistic regression, and restricted cubic splines were employed to analyze the association between thyroid hormone indices and metabolic phenotypes. RESULTS: A total of 4,857 participants (49.6% men; mean age, 42.6 years) were included, with 1,539 having obesity and 235 identified as MHO. Participants in the MHO group exhibited lower levels of TSH, TSHI, TTSI, TFQI, and PTFQI compared with the MHNO group (all p < 0.05), while the differences among MHNO, MUNO, and MUO groups were not statistically significant (all p > 0.05). Among participants with obesity, TSH, TSHI, TTSI, TFQI, and PTFQI were positively associated with metabolic abnormality (all p < 0.05). CONCLUSION: Participants with MHO exhibited higher thyroid hormone sensitivity among various obesity phenotypes, even when compared with those with MHNO. A positive association was observed between metabolic abnormality and thyroid hormone sensitivity, while the trend of TSH was observed to be consistent with sensitivity to thyroid hormone indices in discriminating metabolic abnormality. Hence, TSH has the potential to serve as a convenient index for detecting sensitivity to thyroid hormones and further metabolic conditions.

Case report: Endoscopic Hemoclip treatment for massive hematemesis caused by a Dieulafoy's lesion on duodenal papilla caused acute pancreatitis.

Background: Dieulafoy's lesion is an uncommon cause of hemorrhage of the digestive tract. It often presents with urgent and massive bleeding usually leading to shock, even death. Dieulafoy's lesions have been reported throughout the digestive tract but which occurred on duodenal papilla were particularly rare and presented challenges in the choice of hemostasis. Case presentation: A 66-year-old man with melena for 2 days was admitted. Gastrointestinal endoscopy revealed blood clots covering the duodenal papilla with oozing blood. During the procedure of trying to place a plastic stent into the duodenal papilla first, the hemorrhage began to present pulsating bleeding. The patient went into shock. With consent, two titanium clips were inserted to clamp the bleeding site to stop the bleeding. The patient complained of epigastric pain 14 h after the endoscopy. An abdominal CT scan showed signs of acute pancreatitis. Endoscopy was performed to remove the titanium clips and showed a vessel stump on the duodenal papilla. The patient was discharged from the hospital on the 14th day and followed for 6 months with no recurrence. Conclusion: This case was diagnosed with a Dieulafoy's lesion on the duodenal papilla, which has rarely been reported. Hematemesis was stopped by clamping the vessel stump with titanium clips but caused acute pancreatitis. Reviewing the treatment, electrocoagulation might be a better choice, and life support treatment, including central vena catheterization and an adequate supply of blood products, should be prepared in advance to provide extra time for the stent placement or vascular intervention treatment.