Uric acid-lowering effect of harpagoside and its protective effect against hyperuricemia-induced renal injury in mice.

Hyperuricemia (HUA) is caused by increased synthesis and/or insufficient excretion of uric acid (UA). Long-lasting HUA may lead to a number of diseases including gout and kidney injury. Harpagoside (Harp) is a bioactive compound with potent anti-inflammatory activity from the roots of Scrophularia ningpoensis. Nevertheless, its potential effect on HUA was not reported. The anti-HUA and nephroprotective effects of Harp on HUA mice were assessed by biochemical and histological analysis. The proteins responsible for UA production and transportation were investigated to figure out its anti-HUA mechanism, while proteins related to NF-κB/NLRP3 pathway were evaluated to reveal its nephroprotective mechanism. The safety was evaluated by testing its effect on body weight and organ coefficients. The results showed that Harp significantly reduced the SUA level and protected the kidney against HUA-induced injury but had no negative effect on safety. Mechanistically, Harp significantly reduced UA production by acting as inhibitors of xanthine oxidase (XOD) and adenosine deaminase (ADA) and decreased UA excretion by acting as activators of ABCG2, OAT1 and inhibitors of GLUT9 and URAT1. Moreover, Harp markedly reduced infiltration of inflammatory cells and down-regulated expressions of TNF-α, NF-κB, NLRP3 and IL-1ß in the kidney. Harp was a promising anti-HUA agent.

Fusobacterium nucleatum bacteremia complicated with intracranial Porphyromonas gingivalis and HSV-1 infection: a case report and literature review.

BACKGROUND: Fusobacterium nucleatum (F. nucleatum) belongs to the genus Fusobacterium, which is a gram-negative obligate anaerobic bacterium. Bacteremia associated with F. nucleatum is a serious complication, which is not common in clinic, especially when it is combined with other intracranial pathogenic microorganism infection. We reported for the first time a case of F. nucleatum bacteremia combined with intracranial Porphyromonas gingivalis (P. gingivalis) and herpes simplex virus type 1(HSV-1) infection. CASE PRESENTATION: A 60-year-old woman was admitted to our hospital with a headache for a week that worsened for 2 days. Combined with history, physical signs and examination, it was characterized as ischemic cerebrovascular disease (ICVD). F. nucleatum was detected in blood by matrix-assisted laser desorption/ionization time-offight mass spectrometry (MALDI-TOF-MS). Meanwhile, P. gingivalis and HSV-1 in cerebrospinal fluid (CSF) were identified by metagenome next generation sequencing (mNGS). After a quick diagnosis and a combination of antibiotics and antiviral treatment, the patient recovered and was discharged. CONCLUSION: To our knowledge, this is the first report of intracranial P. gingivalis and HSV-1 infection combined with F. nucleatum bacteremia.

Treatment-naïve people living with HIV aged 50 years or older in Beijing, China, 2010-2020: joinpoint regression model analysis of surveillance data.

INTRODUCTION: As they age, people living with HIV (PLWH) must face new challenges, such as accelerated ageing and higher rates of comorbidities. This study described the characteristics of HIV acquisition among treatment-naïve PLWH aged ≥50 years and <50 years in Beijing from 2010 to 2020, exploring associated risk factors for comorbidities. METHODS: In this cross-sectional study, differences in HIV-related and non-HIV-related characteristics were compared using the t-test, Mann-Whitney U test and chi-square test. Temporal trend data were analysed via joinpoint regression. A multivariate logistic regression model was conducted to analyse the associated factors with PLWH having one or more comorbidities. RESULTS: The proportion of PLWH aged ≥50 years has significantly increased since 2013, with a corresponding increase in homosexual transmission in this age group over the past decade. The proportion of individuals with CD4 counts <200 cells/µl significantly decreased from 2010 to 2013 among PLWH aged ≥50 years and from 2010 to 2014 among those aged <50 years. Delayed initiation of antiretroviral therapy (ART) improved for both age groups over the course of the decade, especially from 2014 to 2020. Compared to PLWH aged <50 years, those aged ≥50 years had a higher proportion of CD4 counts <200 cells/µl, higher levels of plasma HIV RNA load and a higher prevalence of non-HIV-related risk factors. Multivariate analysis revealed that PLWH aged ≥50, male, not single, transmission through heterosexual contact or drug injection, WHO Stage IV, coinfection with hepatitis B virus/hepatitis C virus and CD4 counts <200 cells/µl at the initiation of ART were associated with higher risk of the presence of an HIV comorbidity. CONCLUSIONS: Due to the persistent burden of HIV-related characteristics or symptoms and the increasing prevalence of coexisting comorbidities among treatment-naïve PLWH aged ≥50 years, physicians should provide the highest-quality screening, prevention, treatment and management of coexisting comorbidities, adopting a multidisciplinary approach.

A Comparison of Robotic Versus Laparoscopic Distal Pancreatectomy for Benign or Malignant Lesions: A Meta-Analysis.

Background: The momentum of robotic surgery is increasing, and it has great prospects in pancreatic surgery. It has been widely accepted and expanding to more and more centers. Robotic distal pancreatectomy (RDP) is the most recent advanced minimally invasive approach for pancreatic lesions and malignancies. However, laparoscopic distal pancreatectomy (LDP) also showed good efficacy. We compared the effect of RDP with LDP using a meta-analysis. Methods: From January 2010 to June 2023, clinical trials of RDP versus LDP were determined by searching PubMed, Medline, and EMBASE. A meta-analysis was conducted to compare the effect of RDP with LDP. This meta-analysis evaluated the R0 resection rate, lymph node metastasis rate, conversion to open surgery rate, spleen preservation rate, intraoperative blood loss, postoperative pancreatic fistula, postoperative hospital stay, 90-day mortality rate, surgical cost, and total cost. Results: This meta-analysis included 38 studies. Conversion to open surgery, blood loss, and 90-day mortality in the RDP group were all significantly less than that in the LDP group (P < .05). There was no difference in lymph node resection rate, R0 resection rate, or postoperative pancreatic fistula between the two groups (P > .05). Spleen preservation rate in the LDP group was higher than that in the RDP group (P < .05). Operation cost and total cost in the RDP group were both more than that in the LDP group (P < .05). It is uncertain which group has an advantage in postoperative hospital stay. Conclusions: To some degree, RDP and LDP were indeed worth comparing in clinical practice. However, it may be difficult to determine which is absolute advantage according to current data. Large sample randomized controlled trials are needed to confirm which is better treatment. PROSPERO ID: CRD4202345576.

Diagnostic validity of MRI for central nervous system tuberculosis: protocol for a systematic review and meta-analysis.

INTRODUCTION: Central nervous system tuberculosis (CNSTB) is a severe condition, sometimes associated with a poor prognosis. Early diagnosis of CNSTB remains challenging, considering that conventional methods lack sensitivity or might lead to certain side effects. Herein, we presented a protocol for a systematic review and meta-analysis to assess the diagnostic efficacy of MRI for CNSTB. METHODS AND ANALYSIS: SinoMed, Wanfang database, China National Knowledge Infrastructure, Embase, the Cochrane Library and PubMed will be searched to identify studies reporting on the use of MRI in the diagnosis of CNSTB from database inception to December 2023. The following keywords will be applied: 'Intracranial tuberculosis', 'Cerebral tuberculosis', 'Central nervous system tuberculosis', 'Spinal tuberculous arachnoiditis' and 'Magnetic Resonance Imaging'. Studies that evaluate the diagnostic accuracy of MRI for the diagnosis of CNSTB and report clear reference criteria will be included. Studies from which full true positive, false positive, false negative and true negative values cannot be extracted, those published in languages other than English or Chinese, abstracts not reporting the full text, and case reports will be excluded. Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) will be used to evaluate the methodological quality of each included study. Stata V.15.0 and RevMan V.5.3 will be used to perform a meta-analysis and generate forest plots and summary receiver operating characteristic curves. In case of significant heterogeneity between studies, possible sources of heterogeneity will be explored through subgroup and meta-regression analyses. ETHICS AND DISSEMINATION: This research is based on public databases and does not require ethical approval. Results will be submitted for publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023415690.

Sinapine thiocyanate exhibited anti-colorectal cancer effects by inhibiting KRT6A/S100A2 axis.

Sinapine thiocyanate (ST), an alkaloid existed extensively in seeds of cruciferous plants, exhibits a number of pharmacological effects, including anti-inflammatory and anti-malignancy properties. However, it is still unknown what effects and molecular mechanisms ST has on colorectal cancer (CRC). In the current study, it was indicated that ST inhibited proliferation, colony formation, and apoptosis in vitro, as well as arrested the G1 phase of CRC cells. There was a significant repressive effects of ST on invasion and migration of CRC cells in vitro. RNA-sequencing indicated that 750 differentially expressed genes existed in CRC cells after ST treatment, and enrichment analysis demonstrated that ST obviously decreased the activation of keratinization pathways. Among DEGs enriched in keratinization, keratin 6A (KRT6A) was decreased the most significant, as well as its target gene S100 calcium-binding protein A2 (S100A2). Low expression of KRT6A and S100A2 signatures indicated a favorable prognosis in CRC patients. Moreover, we found overexpression of KRT6A relieved the inhibitory effects of ST in CRC cells. Furthermore, ST inhibited the CRC cell proliferation in vivo, and reduced KRT6A and KI67 expression in xenograft tumor. Taken together, we demonstrated that ST exhibited anti-CRC properties by inhibiting KRT6A/S100A2 axis. It is possible that ST can be used as a treatment for CRC.

Protective effect of water extracts of Veronicastrum latifolium (Hemsl.) Yamazaki on carbon tetrachloride-induced liver fibrosis in mice and its effect on intestinal flora.

Liver fibrosis refers to a reversible event of repair and reconstruction following injury due to various etiologies, and its continuous development will lead to cirrhosis and liver cancer. Abnormal alterations in intestinal microbiota can hasten the development of hepatic fibrosis and damage. Veronicastrum latifolium (Hemsl.) Yamazaki (VLY) is a classic drug applied extensively for managing acute and chronic hepatitis, liver cirrhosis and ascites in ethnic minority areas of Guizhou Province, China, which possesses broad-spectrum pharmacological activities. In view of the crucial role of intestinal microbiota in the development of liver fibrosis, the present study attempted to investigate the effects of VLY aqueous extract on ameliorating CCl4-elicited liver fibrosis in mice and on intestinal microbiota and to explore its possible mechanism. Phytochemical analysis showed that VLY water extract contained a variety of components, particularly rich in organic acids and their derivatives, flavonoids, phenolic acids, nucleotides and their derivatives, carbohydrates and other compounds. VLY water extract remarkably alleviated CCl4-induced liver damage and fibrosis in mice, improved liver histology, and improved liver function abnormalities. VLY water extract also inhibited the activation of hepatic stellate cells and invasion of intrahepatic inflammatory cells. Additionally, sequencing the 16 s rDNA gene revealed that VLY water extract changed the intestinal microbiota composition in liver fibrotic mice. It elevated the Firmicutes/Bacteroidota ratio and enriched the relative Lactobacillus richness, which is capable of mitigating fibrosis and inflammation in impaired liver. In summary, through modulation of inflammation and intestinal microbiota, VLY water extract can reduce the CCl4-elicited liver fibrosis.

The value of histopathology combined with CapitalBio Mycobacterium real-time polymerase chain reaction test for diagnosing spinal tuberculosis.

Purpose: To evaluate the diagnostic efficacy of CapitalBio Mycobacterium real-time polymerase chain reaction assay (CapitalBio test) in spinal tuberculosis (STB). The value of histopathology combined with the CapitalBio test in diagnosing STB was also assessed. Methods: We retrospectively analyzed the medical information of suspected STB. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of histopathology, CapitalBio test, and histopathology combined with CapitalBio test were calculated to evaluate their diagnostic efficacy compared with a composite reference standard. Results: A total of 222 suspected STB patients were included in the study. The sensitivity, specificity, PPV, NPV, and AUC of histopathology for STB were recorded to be 62.0, 98.0, 97.4, 68.3%, and 0.80, respectively. The sensitivity, specificity, PPV, NPV, and AUC of the CapitalBio test were 75.2, 98.0, 97.9, 76.7%, and 0.87, respectively, while that of histopathology combined with the CapitalBio test was 81.0, 96.0, 96.1, 80.8%, and 0.89, respectively. Conclusion: Histopathology and CapitalBio test exhibited high accuracy and are recommended in diagnosing STB. Histopathology combined with the CapitalBio test might give the best efficacy in STB diagnosis.

[Oenothein B inhibits proliferation and migration of breast cancer cells by regulating P53].

The effects of oenothein B(OEB) on the proliferation, apoptosis, invasion, and migration of breast cancer MCF-7 and MDA-MB-231 cells were investigated by cell culture in vitro, network pharmacology, and molecular docking. In vitro cell experiments revealed that OEB inhibited the proliferation and colony formation ability, and promoted the apoptosis and formation of apoptotic bodies in breast cancer cells, as well as inhibited the invasion and migration of breast cancer cells. The targets of OEB were obtained using SwissTargetPrediction database and breast cancer targets were obtained from GeneCards. The targets of OEB and breast cancer were entered separately in Venny 2.1 software to obtain the Venn diagram of common targets of OEB and breast cancer. The common targets of OEB and breast cancer were input into STRING database to construct a protein-protein interaction(PPI) network, which was entered into Cytoscape 3.7.2 software for network topology analysis. Key targets were screened according to protein association strength, and analyzed for KEGG pathway enrichment. Molecular docking of OEB to key targets using AutoDock software revealed that OEB stably bound to the active pocket of P53, while OEB promoted the expression of P53 protein. MCF-7 and MDA-MB-231 cell viability and migration ability increased after silencing P53, and this change was reversed after treatment with OEB. Therefore, this study showed that OEB inhibited the proliferation, migration, and invasion of breast cancer MCF-7 and MDA-MB-231 cells, and promoted the apoptosis of breast cancer MCF-7 and MDA-MB-231 cells, which may be related to the targeted regulation of P53.

Periconceptional Folic Acid Only Versus Multiple Micronutrients Containing Folic Acid and Association with Gestational Diabetes Mellitus - Beijing Municipality, China, 2017-2021.

What is already known about this topic?: Inconsistent results have been reported on the association between periconceptional folic acid only (FAO) or multiple micronutrients containing folic acid (MMFA) supplementation and the risk of gestational diabetes mellitus (GDM) in previous research. What is added by this report?: In a prospective cohort study conducted among pregnant women in Haidian District, Beijing Municipality, it was observed that those who took MMFA demonstrated a higher likelihood of developing GDM in comparison to those who consumed FAO periconceptionally. Interestingly, the increased risk for GDM in pregnant women supplemented with MMFA compared to FAO was primarily due to changes in fasting plasma glucose. What are the implications for public health practice?: It is highly recommended that women prioritize the use of FAO in order to yield potential benefits in the prevention of GDM.

Amelioration effects of α-viniferin on hyperuricemia and hyperuricemia-induced kidney injury in mice.

BACKGROUND: α-Viniferin, the major constituent of the roots of Caragana sinica (Buc'hoz) Rehder with a trimeric resveratrol oligostilbenoid skeleton, was demonstrated to possess a strong inhibitory effect on xanthine oxidase in vitro, suggesting it to be a potential anti-hyperuricemia agent. However, the in vivo anti-hyperuricemia effect and its underlying mechanism were still unknown. PURPOSE: The current study aimed to evaluate the anti-hyperuricemia effect of α-viniferin in a mouse model and to assess its safety profile with emphasis on its protective effect on hyperuricemia-induced renal injury. METHODS: The effects were assessed in a potassium oxonate (PO)- and hypoxanthine (HX)-induced hyperuricemia mice model by analyzing the levels of serum uric acid (SUA), urine uric acid (UUA), serum creatinine (SCRE), serum urea nitrogen (SBUN), and histological changes. Western blotting and transcriptomic analysis were used to identify the genes, proteins, and signaling pathways involved. RESULTS: α-Viniferin treatment significantly reduced SUA levels and markedly mitigated hyperuricemia-induced kidney injury in the hyperuricemia mice. Besides, α-viniferin did not show any obvious toxicity in mice. Research into the mechanism of action of α-viniferin revealed that it not only inhibited uric acid formation by acting as an XOD inhibitor, but also reduced uric acid absorption by acting as a GLUT9 and URAT1 dual inhibitor as well as promoted uric acid excretion by acting as a ABCG2 and OAT1 dual activator. Then, 54 differentially expressed (log2 FPKM ≥ 1.5, p ≤ 0.01) genes (DEGs) repressed by the treatment of α-viniferin in the hyperuricemia mice were identified in the kidney. Finally, gene annotation results revealed that downregulation of S100A9 in the IL-17 pathway, of CCR5 and PIK3R5 in the chemokine signaling pathway, and of TLR2, ITGA4, and PIK3R5 in the PI3K-AKT signaling pathway were involved in the protective effect of α-viniferin on the hyperuricemia-induced renal injury. CONCLUSIONS: α-Viniferin inhibited the production of uric acid through down-regulation of XOD in hyperuricemia mice. Besides, it also down-regulated the expressions of URAT1 and GLUT9 and up-regulated the expressions of ABCG2 and OAT1 to promote the excretion of uric acid. α-Viniferin could prevent hyperuricemia mice from renal damage by regulating the IL-17, chemokine, and PI3K-AKT signaling pathways. Collectively, α-viniferin was a promising antihyperuricemia agent with desirable safety profile. This is the first report of α-viniferin as an antihyperuricemia agent.

Association between maternal metabolic profiles in pregnancy, dietary patterns during lactation and breast milk leptin: a retrospective cohort study.

Breast milk leptin plays a potential role in preventing childhood obesity. However, the associations of breast milk leptin with maternal metabolism in pregnancy and dietary patterns during lactation are still unclear. We aimed to explore associations of breast milk leptin with maternal metabolic profiles in pregnancy and dietary patterns during lactation. A total of 332 participants were recruited for this retrospective cohort study. Breast milk samples were collected at approximately 6 weeks postpartum. Breast milk leptin and twenty-three metabolic profiles in pregnancy were measured in this study. A semi-quantitative FFQ was used to gather dietary information during lactation. Both principal component analysis and the diet balance index were used to derive dietary patterns. Among twenty-three maternal metabolic profiles, maternal serum glucose (ß = 1·61, P = 0·009), γ-glutamyl transferase (ß = 0·32, P = 0·047) and albumin (ß = -2·96, P = 0·044) in pregnancy were correlated with breast milk leptin. All dietary patterns were associated with breast milk leptin. Given the joint effects of maternal metabolism in pregnancy and dietary patterns during lactation, only diet quality distance was significantly associated with leptin concentrations in breast milk (low level v. almost no diet problem: ß = -0·46, P = 0·011; moderate/high level v. almost no diet problem: ß = -0·43, P = 0·035). In conclusion, both maternal metabolism in pregnancy and dietary patterns during lactation were associated with breast milk leptin. Maternal diet balance during lactation was helpful to improve breast milk leptin concentration.

Temporal Trends of Clinical Characteristics and Treatments in People Living with HIV at the Initiation of Antiretroviral Therapy - Beijing Municipality, China, 2010-2020.

What is already known about this topic?: Antiretroviral therapy (ART) eligibility criteria and treatment regimens were updated in national guidelines. However, whether treatment was timely and followed guidelines was under-assessed. What is added by this report?: Among 22,591 people living with human immunodeficiency virus (PLWH) who initiated ART in Beijing between 2010 and 2020, the time from diagnosis to initiating ART decreased, the clinical condition of PLWH improved, and ART regimens changed in accordance with guidelines. What are the implications for public health practice?: Over the past decade, improvements in clinical status have been observed among PLWH; however, a proportion of PLWH remain who started ART late. Early linkage to human immunodeficiency virus (HIV) care should be further improved.

Clinical Application of the Mycobacterium tuberculosis-RNA Assay of Pericardial Tissue Specimens in the Diagnosis of Tuberculous Pericarditis.

Purpose: To assess the accuracy of the Mycobacterium tuberculosis (MTB)-RNA assay using pericardial tissue specimens for tuberculous pericarditis (TBP) diagnosis. Methods: MTB culture and MTB-RNA assay were performed for patients with suspected TBP. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of these two assays were analyzed. Results: This study included 79 patients. The sensitivity, specificity, PPV, NPV, and AUC were 28.1% (18/64), 100.0% (15/15), 100.0% (18/18), 24.6% (15/61), and 0.64 for the MTB culture and 37.5% (24/64), 100.0% (15/15), 100.0% (24/24), 27.3% (15/55), and 0.69 for the MTB-RNA assay, respectively. Patients with positive pericardial tissue culture were defined as having definite TBP; in other words, culture was the gold standard for this group of patients and had a sensitivity, specificity, PPV, and NPV of 100% and an AUC of 1.00. However, these values were found to be 72.2% (13/18), 100.0% (15/15), 100.0% (13/13), 75.0% (15/20), and 0.86 for the MTB-RNA assay, respectively. Among patients with probable TBP (culture-negative patients), the sensitivity, specificity, NPV, and AUC of MTB culture were 0.0% (0/46), 100.0% (15/15), 24.6% (15/61), and 0.50, respectively, but the PPV could not be determined. These values were found to be 23.9% (11/46), 100.0% (15/15), 100.0% (11/11), 30.0% (15/50), and 0.62 for the MTB-RNA assay, respectively. Conclusion: MTB-RNA assay using pericardial tissues had limited diagnostic efficacy for TBP. In culture-positive TBP, the diagnostic accuracy of MTB-RNA was good. In contrast, in culture-negative TBP, its diagnostic accuracy was unsatisfactory.

Association between cooking fuel and folate insufficiency among pregnant women in Northern China.

This study explored whether using a coal or biomass stove for cooking was associated with a greater risk of red blood cell (RBC) folate insufficiency among pregnant women compared to using clean energy. A researcher-designed questionnaire was used to collect information on exposure-related factors and confounding factors. RBC folate concentrations were examined by microbiological assay. Binary logistic regression analysis was used to identify factors related to RBC folate insufficiency. The use of coal or firewood for cooking was associated with an increased risk of RBC folate insufficiency (<906 nmol/L) compared to gas. In subgroup analyses, associations between the use of polluting cooking fuels and folate insufficiency were positive for both urban and rural residents and statistically significant for rural women. Efforts to promote the use of clean energy and proper ventilation, especially in rural areas, are recommended to improve the health of pregnant women and their offspring.

The significance of EphA2-regulated Wnt/ß-catenin signal pathway in promoting the metastasis of HBV-related hepatocellular carcinoma.

BACKGROUND: Hepatitis B virus (HBV) infection is closely associated with the malignant progression of hepatocellular carcinoma (HCC). However, the mechanism involved in the HBV-related HCC development remains poorly understood. Hence, the aim of this study is to investigate the regulatory mechanism of EphA2-induced epithelial-mesenchymal transition (EMT) in the metastasis of HBV-related HCC cells. METHODS AND RESULTS: The expression level of EphA2 was determined in HBV-related human HCC cells. Then, the effects of EphA2 silencing on the EMT-associated proteins, the Wnt/ß-catenin signal pathway and the metastatic potential of HBV-related HCC cells were evaluated. Finally, the inhibitory role of Entecavir (a potent antiviral drug for HBV) on EphA2-induced EMT was explored. The present study revealed that the EphA2 expression level was increased in HBV-related HCC cells compared with non-related HCC cells. Following EphA2 knockdown, the downregulation of Vimentin, ß-catenin and p-GSK-3ßSer9 expressions, the upregulation of E-cadherin expression, and the suppressed migration and invasion ability of HBV-related HCC cells were found. Additionally, Entecavir was proved to have a significant inhibitory effect on EphA2-induced EMT via attenuating the Wnt/ß-catenin signal pathway. CONCLUSIONS: In this study, we found that EphA2-induced EMT was involved in the enhanced metastatic potential of HBV-related HCC cells through the activation of the Wnt/ß-catenin signal pathway.

JUND/linc00976 promotes cholangiocarcinoma progression and metastasis, inhibits ferroptosis by regulating the miR-3202/GPX4 axis.

Long noncoding RNAs (lncRNAs) are a novel class of noncoding RNAs that have emerged as critical regulators and biomarkers in various cancers. Nevertheless, the expression profile and mechanistic function of lncRNAs in cholangiocarcinoma (CCA) remain unclear. Herein, we examined the expression levels of linc00976 in clinical specimens and cell lines using reverse transcription-quantitative PCR. In total, 50 patients with CCA were enrolled to analyze the correlation between linc00976 expression and clinical characteristics of CCA. Loss- and gain-of-function experiments were performed to investigate the biological effects of linc00976 on proliferation, ferroptosis, migration, and invasion of CCA cells in vitro and in vivo. In situ hybridization, RNA immunoprecipitation, bioinformatic databases, RNA pull-down assay, a dual-luciferase reporter assay, mRNA sequencing, chromatin immunoprecipitation-PCR, and rescue experiments were performed to elucidate the underlying mechanisms of linc00976-induced competitive endogenous RNA regulatory networks. We characterized a novel and abundant lncRNA, linc00976, that functions as a pro-oncogenic regulator of CCA progression. Compared with normal controls, linc00976 was dramatically upregulated in CCA tissue samples and cell lines. Patients with CCA exhibiting high linc00976 expression had a highly advanced clinical stage, substantial lymph node metastasis, and poor overall survival. Knockdown of linc00976 significantly repressed proliferation and metastasis and promoted ferroptosis of CCA cells both in vitro and in vivo, whereas linc00976 overexpression exerted the opposite effect. Mechanistically, linc00976 competitively interacted with miR-3202 to upregulate GPX4 expression, thus contributing to the malignant biological behavior of CCA cells. Moreover, we demonstrated that JUND specifically interacts with the linc00976 promoter and activates linc00976 transcription. Accordingly, JUND promotes linc00976 transcription, and linc00976 plays a crucial role in accelerating CCA tumorigenesis and metastasis and inhibiting ferroptosis by modulating the miR-3202/GPX4 axis. These findings suggest that targeting linc00976 may afford a promising therapeutic strategy for patients with CCA.

Development and validation of lymph node ratio-based nomograms for primary duodenal adenocarcinoma after surgery.

Background: The prediction models for primary duodenal adenocarcinoma (PDA) are deficient. This study aimed to determine the predictive value of the lymph node ratio (LNR) in PDA patients and to establish and validate nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) for PDAs after surgical resection. Methods: We extracted the demographics and clinicopathological information of PDA patients between 2004 and 2018 from the Surveillance, Epidemiology and End Results database. After screening cases, we randomly divided the enrolled patients into training and validation groups. X-tile software was used to obtain the best cut-off value for the LNR. Univariate and multivariate Cox analyses were used in the training group to screen out significant variables to develop nomograms. The predictive accuracy of the nomograms was evaluated by the concordance index (C-index), calibration curves, area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). Finally, four risk groups were created based on quartiles of the model scores. Results: A total of 978 patients were included in this study. The best cut-off value for the LNR was 0.47. LNR was a negative predictive factor for both OS and CSS. Age, sex, grade, chemotherapy and LNR were used to construct the OS nomogram, while age, grade, chemotherapy, the number of lymph nodes removed and LNR were incorporated into the CSS nomogram. The C-index, calibration curves and AUC of the training and validation sets revealed their good predictability. DCA showed that the predictive value of the nomograms was superior to that of the American Joint Committee on Cancer (AJCC) TNM staging system (8th edition). In addition, risk stratification demonstrated that patients with higher risk correlated with poor survival. Conclusions: The LNR was an adverse prognostic determinant for PDAs. The nomograms provided an accurate and applicable tool to evaluate the prognosis of PDA patients after surgery.

Central adiposity increases the odds for plasma folate deficiency among Chinese women of reproductive age.

Objective: To explore the association between adiposity and plasma folate deficiency odds among women of reproductive age in China. Methods: A cross-sectional survey on nutritional status among women of reproductive aged 18-30 years in 2005-2006 in China was conducted. General adiposity was defined as body mass index (BMI) ≥24 kg/m2, and central adiposity was defined as waist circumference >80 cm. A plasma folate concentration <10.5 nmol/L (measured through microbiological assay) was defined as plasma folate deficiency. Odds ratios (ORs) and 95% confidence intervals (CIs) for plasma folate deficiency were calculated using a logistic regression model, with adjustment for potential confounders. Results: A total of 3,076 women of reproductive age were included in the final analysis. Compared to women with normal BMI and WC, women with both general and central adiposity had the highest odds for plasma folate deficiency (OR = 3.107, 95% CI: 1.819-5.307). Women with exclusively central adiposity had excess odds for plasma folate deficiency (WC > 80 cm, BMI <24 kg/m2; OR = 2.448, 95% CI: 1.144-5.241), which was higher than women with exclusively general adiposity (BMI ≥ 24 kg/m2, WC ≤ 80 cm; OR = 1.709, 95% CI: 1.259-2.319). The combined use of BMI and WC can detect more women (11.7%) at higher plasma folate deficiency odds than either used alone. Conclusions: Women with central adiposity in normal weight have higher odds for plasma folate deficiency than those with general obesity only. Early screening for central adiposity among women of reproductive age would be meaningful to prevent folate deficiency and improve life-cycle health.

A specific immune signature for predicting the prognosis of glioma patients with IDH1-mutation and guiding immune checkpoint blockade therapy.

Isocitrate dehydrogenase (IDH1) is frequently mutated in glioma tissues, and this mutation mediates specific tumor-promoting mechanisms in glioma cells. We aimed to identify specific immune biomarkers for IDH1-mutation (IDH1mt) glioma. The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) were used to obtain RNA sequencing data and clinical characteristics of glioma tissues, while the stromal and immune scores of TCGA glioma tissues were determined using the ESTIMATE algorithm. Differentially expressed genes (DEGs), the protein-protein interaction(PPI) network, and least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were used to select hub genes associated with stroma and immune scores and the prognoses of patients and to construct the risk model. The practicability and specificity of the risk model in both IDH1mt and IDH1-wildtype (wtIDH1) gliomas in TCGA and CGGA were evaluated. Molecular mechanisms, immunological characteristics and benefits of immune checkpoint blockade therapy in glioma tissues with IDH1mt were analyzed using GSEA, immunohistochemical staining, CIBERSORT, and T-cell dysfunction and exclusion (TIDE) analysis. The overall survival rate for IDH1mt-glioma patients with high stroma/immune scores was lower than that for those with low stroma/immune scores. A total of 222 DEGs were identified in IDH1mt glioma tissues with high stroma/immune scores. Among them, 72 genes had interactions in the PPI network, while three genes, HLA-DQA2, HOXA3, and SAA2, were selected as hub genes and used to construct risk models classifying patients into high- and low-risk score groups, followed by LASSO and Cox regression analyses. This risk model showed prognostic value in IDH1mt glioma in both TCGA and CCGA; nevertheless, the model was not suitable for wtIDH1 glioma. The risk model may act as an independent prognostic factor for IDH1mt glioma. IDH1mt glioma tissues from patients with high-risk scores showed more infiltration of M1 and CD8 T cells than those from patients with low-risk scores. Moreover, TIDE analysis showed that immune checkpoint blockade(ICB) therapy was highly beneficial for IDH1mt patients with high-risk scores. The risk model showed specific potential to predict the prognosis of IDH1mt-glioma patients, as well as guide ICB, contributing to the diagnosis and therapy of IDH1mt-glioma patients.