ABSTRACT
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.
Subject(s)
Glycosides , Hyperuricemia , NLR Family, Pyrin Domain-Containing 3 Protein , Pyrans , Uric Acid , Animals , Hyperuricemia/drug therapy , Hyperuricemia/metabolism , Uric Acid/blood , Male , Glycosides/pharmacology , Glycosides/therapeutic use , Pyrans/pharmacology , Pyrans/therapeutic use , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Kidney/drug effects , Kidney/pathology , Kidney/metabolism , NF-kappa B/metabolism , Mice, Inbred C57BLABSTRACT
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.
Subject(s)
Bacteremia , Fusobacterium Infections , Herpes Simplex , Herpesvirus 1, Human , Female , Humans , Middle Aged , Porphyromonas gingivalis , Fusobacterium nucleatum , Herpesvirus 1, Human/genetics , Base Composition , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA , Herpes Simplex/complications , Herpes Simplex/diagnosis , Herpes Simplex/drug therapy , Bacteremia/complications , Bacteremia/diagnosis , Bacteremia/drug therapy , Fusobacterium Infections/complications , Fusobacterium Infections/diagnosis , Fusobacterium Infections/drug therapyABSTRACT
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.
Subject(s)
Milk, Human , Pediatric Obesity , Pregnancy , Female , Child , Humans , Milk, Human/chemistry , Leptin , Retrospective Studies , Lactation , Diet , MetabolomeABSTRACT
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.
Subject(s)
Carcinoma, Hepatocellular , Hepatitis B , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/metabolism , beta Catenin/genetics , beta Catenin/metabolism , Liver Neoplasms/metabolism , Hepatitis B virus , Glycogen Synthase Kinase 3 beta/metabolism , Cell Line, Tumor , Epithelial-Mesenchymal Transition/genetics , Hepatitis B/complications , Hepatitis B/genetics , Signal Transduction , Wnt Signaling Pathway , Cell Proliferation , Cell Movement/geneticsABSTRACT
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.
Subject(s)
Air Pollution, Indoor , Pregnant Women , Humans , Female , Pregnancy , Folic Acid/analysis , Air Pollution, Indoor/adverse effects , Air Pollution, Indoor/analysis , Coal/toxicity , Cooking , China/epidemiologyABSTRACT
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.
Subject(s)
Breast Neoplasms , Humans , Female , Cell Proliferation , Breast Neoplasms/drug therapy , Tumor Suppressor Protein p53/genetics , Molecular Docking SimulationABSTRACT
Objective: The target of this work was to analyze the clinical characteristics and construct nomograms to predict prognosis in patients with cervical adenosquamous carcinoma (ASC). Methods: A total of 788 ASC patients were tracked in the Surveillance, Epidemiology and End Results database. We compared the clinical characteristics and prognostic factors of ASC. Cox regression models were established, and nomograms were constructed and verified. Results: ASC patients have lower age levels and higher histological grades than patients with squamous cell carcinoma. Nomograms were constructed with good consistency and feasibility in clinical practice. The C-indices for overall survival and cancer-specific survival were 0.783 and 0.787, respectively. Conclusion: ASC patients have unique clinicopathological and prognostic characteristics. Nomograms were successfully constructed and verified.
Subject(s)
Carcinoma, Adenosquamous/mortality , Carcinoma, Squamous Cell/mortality , Nomograms , Uterine Cervical Neoplasms/mortality , Adult , Carcinoma, Adenosquamous/diagnosis , Carcinoma, Adenosquamous/pathology , Carcinoma, Adenosquamous/therapy , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Cervix Uteri/pathology , Clinical Decision-Making/methods , Feasibility Studies , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Risk Assessment/methods , Risk Assessment/statistics & numerical data , SEER Program/statistics & numerical data , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/therapyABSTRACT
OBJECTIVE: To establish a risk prediction model for pancreatic fistula according to the pancreatic fistula standards of the 2016 edition. METHODS: Clinical data from 223 patients with PD admitted to Tianjin Third Central Hospital from January 2016 to December 2020 were retrospectively analyzed. Patients were divided into modeling (January 2016 to December 2018) and validation (January 2019 to December 2020) sets according to the time of admission. The risk factors for postoperative pancreatic fistula (POPF) were screened by univariate and multivariate logistic regression analyses, and a risk prediction model for POPF was established in the modeling set. This score was tested in the validation set. RESULTS: Logistic regression analysis showed that the main pancreatic duct index and CT value were independent risk factors according to the 2016 pancreatic fistula grading standard, based on which a risk prediction model for POPF was established. Receiver operating characteristic curve analysis showed that the area under the curve was 0.775 in the modeling set and 0.848 in the validation set. CONCLUSION: The main pancreatic duct index and CT value of the pancreas are closely related to the occurrence of pancreatic fistula after PD, and the established risk prediction model for pancreatic fistula has good prediction accuracy.
Subject(s)
Pancreatic Fistula , Pancreaticoduodenectomy , Humans , Pancreas/surgery , Pancreatic Fistula/epidemiology , Pancreatic Fistula/etiology , Pancreaticoduodenectomy/adverse effects , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Prognosis , ROC Curve , Retrospective Studies , Risk FactorsABSTRACT
Pseudostellaria heterophylla is used in China not only as a functional food but also as an herb to tonify the spleen, enhance immunity, and treat palpitation. Our previous investigation showed that a fraction enriched in glycosides obtained from the roots of P. heterophylla possessed pronounced protective effects on H9c2 cells against CoCl2-induced hypoxic injury. However, the active compounds responsible for the observed effects were still unknown. In the current investigation, pseudosterins A-C (1-3), three new alkaloids with a 1-ethyl-3-formyl-ß-carboline skeleton, together with polydatin, have been isolated from the active fraction. Their structures were elucidated on the basis of spectroscopic analysis and quantum chemical calculations. The four compounds showed cardioprotective effects against sodium hydrosulfite-induced hypoxia-reoxygenation injury in H9c2 cells, with the three alkaloids being more potent. This is also the first report of alkaloids with a ß-carboline skeleton isolated from P. heterophylla as cardioprotective agents.
Subject(s)
Alkaloids/pharmacology , Carbolines/pharmacology , Cardiotonic Agents/pharmacology , Caryophyllaceae/chemistry , Plant Extracts/pharmacology , Alkaloids/chemistry , Animals , Carbolines/chemistry , Cardiotonic Agents/chemistry , Cell Line , China , Glycosides/chemistry , Glycosides/pharmacology , Hypoxia/drug therapy , Plant Extracts/chemistry , Plant Roots/chemistry , RatsABSTRACT
Acetaminophen (APAP) overdose is very common worldwide and has been widely recognized as the leading cause of drug-induced liver injury in the Western world. In our previous investigation, auriculatone, a natural product firstly obtained from Aster auriculatus, has demonstrated a potent protective effect against APAP-induced hepatotoxicity in HL-7702 cells. However, the poor water solubility and low bioavailability restrict its application. Auriculatone sulfate (AS) is a sulfated derivative of auriculatone with highly improved water-solubility. Hepatoprotective effects against APAP-induced liver injury (AILI) showed that intragastric pretreatment with AS at 50 mg/kg almost completely prevented mice against APAP-induced increases of serum alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and ATPase. Histological results showed that AS could protect the liver tissue damage. In addition, AS pretreatment not only significantly retained hepatic malondialdehyde and the activities of glutathione, superoxide dismutase, and glutathione peroxidase at normal levels, but also markedly suppressed the increase of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 levels in mouse liver caused by overdose APAP. Immunohistochemical analysis showed that AS obviously attenuated the expression of CD45 and HNE in liver tissue. Further mechanisms of action investigation showed that inhibition of cytochrome P450 3A11 (CYP 3A11) and CYP2E1 enzymatic activities (but not that of CYP1A2) was responsible for APAP bioactivation. In conclusion, AS showed a hepatoprotective effect against AILI through alleviating oxidative stress and inflammation and inhibiting CYP-mediated APAP bioactivation. It may be an effective hepatoprotective agent for AILI and other forms of human liver disease.
Subject(s)
Acetaminophen/adverse effects , Analgesics, Non-Narcotic/adverse effects , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/etiology , Protective Agents/pharmacology , Animals , Cytokines/metabolism , Inflammation Mediators/metabolism , Liver/drug effects , Liver/metabolism , Liver/pathology , Mice , Mitochondria/drug effects , Mitochondria/metabolism , Molecular Structure , Oxidative Stress/drug effects , Protective Agents/chemistry , Reactive Oxygen Species/metabolismABSTRACT
Chemokine receptor type 4 (CXCR4) has been suggested to regulate cell migration and invasion in human somatic cells. However, its role in human oocytes and embryos has not been investigated directly. Here we show that CXCR4 mRNA was initially expressed at the 4-cell stage, and its expression gradually increased until the blastocyst stage, whereas its protein was detectable only after the 8-cell stage. In addition, CXCR4 mRNA and protein were expressed in the inner cell mass (ICM) and trophectoderm (TE) cell of the blastocyst. Furthermore, we collected embryos from women whose embryos had undergone successful implantation (SI) and those whose embryos had failed implantation (FI) in their fresh cycles. TE cells from the FI group had reduced CXCR4 mRNA expression relative to those from the SI group but not in the ICM. Through ICM replacement, we constructed mouse blastocysts in which Cxcr4 was specifically knocked down in TE cells to simulate the CXCR4 expression profile of human blastocysts from the FI group. In this case, we found that the implantation rate significantly decreased after transfer of reconstructed embryos. Bioinformatic analysis indicated that CXCR4 can induce cell apoptosis and migration mediated by Rho signaling. This hypothesis was confirmed by invasion and migration experiments, using a human trophoblast cell line. The present study is the first to explore the characteristics of CXCR4 expression using human oocytes and embryos and suggests that CXCR4 is required upstream of TE cell apoptosis and migration. CXCR4 expression is a potential biomarker to predict implantation competence during assisted reproductive technologies.
Subject(s)
Blastocyst/metabolism , Cell Movement/physiology , Embryo Implantation/physiology , Receptors, CXCR4/metabolism , Trophoblasts/metabolism , Animals , Apoptosis/physiology , Cell Line , Fertilization in Vitro , Gene Expression Regulation, Developmental , Humans , Mice , Receptors, CXCR4/genetics , Signal Transduction/physiologySubject(s)
Carcinoma, Hepatocellular , Colorectal Neoplasms , Hepatectomy/methods , Liver Neoplasms , Liver , Portal Vein/surgery , Adult , Carcinoma, Hepatocellular/secondary , Carcinoma, Hepatocellular/surgery , Colorectal Neoplasms/secondary , Colorectal Neoplasms/surgery , Female , Hepatectomy/adverse effects , Humans , Ligation , Liver/blood supply , Liver/surgery , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Male , Middle AgedABSTRACT
Trophoblast stem cells differentiate into different trophoblast cell populations that are indispensable for successful pregnancy through interactions with the maternal uterine decidua. Rho GTPases play an important role in the regulation of trophoblast stem cell (TSC) self-renewal and differentiation; however, the role of Rho GDP-dissociation inhibitors (Rho GDIs) remains unclear. Here we report that overexpression of Rho GDIalpha resulted in rapid apoptosis of TSCs, while its knockdown promoted proliferation. Moreover, Rho GDIalpha knockdown also enhanced TSC invasion. Collectively, these results establish a potential mechanism whereby TSCs can balance growth and apoptosis, and thus ensure normal fetal development.
Subject(s)
Apoptosis/physiology , Cell Movement/physiology , Stem Cells/metabolism , Trophoblasts/metabolism , rho Guanine Nucleotide Dissociation Inhibitor alpha/metabolism , Animals , Cell Differentiation/physiology , Cell Proliferation/physiology , Cell Survival/physiology , Female , Pregnancy , Rabbits , Stem Cells/cytology , Trophoblasts/cytologyABSTRACT
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.
ABSTRACT
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.
Subject(s)
Tuberculosis, Central Nervous System , Tuberculosis , Humans , Systematic Reviews as Topic , Meta-Analysis as Topic , Magnetic Resonance Imaging/methods , Research DesignABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
Subject(s)
HIV Infections , Humans , Male , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Beijing/epidemiology , Cross-Sectional Studies , Risk Factors , China/epidemiology , HIVABSTRACT
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.
Subject(s)
Laparoscopy , Pancreatectomy , Robotic Surgical Procedures , Humans , Length of Stay , Pancreatectomy/methods , Pancreatic Fistula , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/pathology , Postoperative Complications/epidemiology , Postoperative Complications/surgery , Retrospective Studies , Robotics , Treatment Outcome , Pancreatic Diseases/pathology , Pancreatic Diseases/surgery , Pancreas/pathology , Pancreas/surgeryABSTRACT
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.