Integrating trans-omics, cellular experiments and clinical validation to identify ILF2 as a diagnostic serum biomarker and therapeutic target in gastric cancer.

BACKGROUND: Gastric cancer (GC) lacks serum biomarkers with clinical diagnostic value. Multi-omics analysis is an important approach to discovering cancer biomarkers. This study aimed to identify and validate serum biomarkers for GC diagnosis by cross-analysis of proteomics and transcriptomics datasets. METHODS: A cross-omics analysis was performed to identify overlapping differentially expressed genes (DEGs) between our previous aptamer-based GC serum proteomics dataset and the GC tissue RNA-Seq dataset in The Cancer Genome Atlas (TCGA) database, followed by lasso regression and random forest analysis to select key overlapping DEGs as candidate biomarkers for GC. The mRNA levels and diagnostic performance of these candidate biomarkers were analyzed in the original and independent GC datasets to select valuable candidate biomarkers. The valuable candidate biomarkers were subjected to bioinformatics analysis to select those closely associated with the biological behaviors of GC as potential biomarkers. The clinical diagnostic value of the potential biomarkers was validated using serum samples, and their expression levels and functions in GC cells were validated using in vitro cell experiments. RESULTS: Four candidate biomarkers (ILF2, PGM2L1, CHD7, and JCHAIN) were selected. Their mRNA levels differed significantly between tumor and normal tissues and showed different diagnostic performances for GC, with areas under the receiver operating characteristic curve (AUROCs) of 0.629-0.950 in the TCGA dataset and 0.736-0.840 in the Gene Expression Omnibus (GEO) dataset. In the bioinformatics analysis, only ILF2 (interleukin enhancer-binding factor 2) gene levels were associated with immune cell infiltration, some checkpoint gene expression, chemotherapy sensitivity, and immunotherapy response. Serum levels of ILF2 were higher in GC patients than in controls, with an AUROC of 0.944 for the diagnosis of GC, and it was also detected in the supernatants of GC cells. Knockdown of ILF2 by siRNA significantly reduced the proliferation and colony formation of GC cells. Overexpression of ILF2 significantly promotes the proliferation and colony formation of gastric cancer cells. CONCLUSIONS: Trans-omics analysis of proteomics and transcriptomics is an efficient approach for discovering serum biomarkers, and ILF2 is a potential diagnostic biomarker and therapeutic target of gastric cancer.

The Index sAGP is Valuable for Distinguishing Atypical Hepatocellular Carcinoma from Atypical Benign Focal Hepatic Lesions.

Purpose: The differential diagnosis of atypical hepatocellular carcinoma (aHCC) and atypical benign focal hepatic lesions (aBFHL) usually depends on pathology. This study aimed to develop non-invasive approaches based on conventional blood indicators for the differential diagnosis of aHCC and aBFHL. Patients and Methods: Hospitalized patients with pathologically confirmed focal hepatic lesions and their clinical data were retrospectively collected, in which patients with HCC with serum alpha-fetoprotein (AFP) levels of ≤200 ng/mL and atypical imaging features were designated as the aHCC group (n = 224), and patients with benign focal hepatic lesions without typical imaging features were designated as the aBFHL group (n = 178). The performance of indexes (both previously reported and newly constructed) derived from conventional blood indicators by four mathematical operations in distinguishing aHCC and aBFHL was evaluated using the receiver operating characteristic (ROC) curve and diagnostic validity metrics. Results: Among ten previously reported derived indexes related to HCC, the index GPR, the ratio of γ-glutamyltransferase (GGT) to platelet (PLT), showed the best performance in distinguishing aHCC from aBFHL with the area under ROC curve (AUROC) of 0.853 (95% CI 0.814-0.892), but the other indexes were of little value (AUROCs from 0.531 to 0.700). A new derived index, sAGP [(standardized AFP + standardized GGT)/standardized PLT], was developed and exhibited AUROCs of 0.905, 0.894, 0.891, 0.925, and 0.862 in differentiating overall, BCLC stage 0/A, TNM stage I, small, and AFP-negative aHCC from aBFHL, respectively. Conclusion: The sAGP index is an efficient, simple, and practical metric for the non-invasive differentiation of aHCC from aBFHL.

Evolution and Trends of Aptamers in Cancer Research: A Bibliometric Analysis of the Literature over the Last Decade.

OBJECTIVE: Aptamers are increasingly applied in cancer research. Here, we have performed the first bibliometric analysis to demonstrate the evolution of aptamers in cancer research over the past decade and to reveal future trends. METHOD: Original articles and reviews on aptamers in cancer research published from 2013 to 2022 were retrieved from the Web of Science Core Collection database. VOSviewer, CiteSpace, and R software were used for bibliometric analysis of the literature and visualization of the results. RESULTS: A total of 1627 eligible publications were analyzed. Annual and cumulative publications have been found to be steadily increased. China was the most productive country (884 publications) and Hunan University was the most productive institution (97 publications). The United States had the highest level of international collaboration (betweenness centrality = 0.55). Wei-Hong Tan was the most productive author (68 publications) and Craig Tuerk was the most cited author (387 citations). Analytical Chemistry and Biosensors and Bioelectronics were the most influential journals in this field. Three major themes were identified: aptamer selection techniques, aptamer-targeted drug delivery, and aptasensors for cancer detection. The research hotspots have shifted from aptamer selection, targeted drug delivery, molecular imaging, and biomarker detection to electrochemical aptasensors and therapeutic applications. The future may focus on high specificity and affinity in aptamer selection, aptasensor fabrication, aptamer- targeted drug delivery, and therapeutic aptamer development. CONCLUSION: The field of aptamers in cancer research has been steadily developing over the past decade, and future research may focus on aptamer application in cancer detection and therapy and the improvement of aptamer selection.

Early outcomes of anterior segment parameters in patients with high myopia after implantable collamer lens V4c implantation / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To study the early outcomes of anterior segment parameters after implantation of an implantable collamer lens with a central hole(ICL V4c)in patients with high myopia.METHODS:A total of 82 cases(160 eyes)with high myopia, including 42 males(82 eyes)and 40 females(78 eyes), aged 26.0±4.6(21 to 37)years, who underwent ICL V4c implantation at our institution from February 2019 to September 2022 and were followed up for 1 a, were included. The general characteristics of the anterior segment of the eye were measured preoperatively: spherical equivalent, mean horizontal corneal curvature, white-to-white(WTW), and axial length(AL); intraocular pressure(IOP), endothelial cell density(ECD), central anterior chamber depth(CACD), anterior chamber volume(ACV)and anterior chamber angle(ACA)were measured preoperatively and at 1 d, 1 wk, 1, 3 and 6 mo postoperatively. Furthermore, the distance from the centre of the posterior surface of the ICL V4c optical zone to the anterior surface of the lens(vault)was measured at 1 d, 1 wk, 1, 6 mo, and 1 a after surgery.RESULTS: The mean preoperative spherical equivalent of the patients was -7.56±2.55 D, mean horizontal corneal curvature was 42.89±1.47 D, WTW was 11.64±0.37 mm, and AL was 26.64±0.93 mm. The baseline IOP was 15.97±2.13 mmHg, and the differences in IOP at each time point after ICL V4c implantation compared to preoperative were not statistically significant(F=0.875, P=0.504); ECD was 2 989.30±140.78 cells/mm2 at baseline, and ECD at 6 mo after ICL V4c implantation was not statistically significant compared with preoperative ECD(t=1.475, P=0.142); CACD was 3.19±0.21 mm at baseline, and ACV was 210.30±27.7 mm3, and CACD and ACV were significantly lower than preoperative at all postoperative time points(F=111.10, 288.38, all P<0.001). The baseline ACA was 35.44°±11.27°, and the ACA at each time point after ICL V4c implantation was significantly lower than preoperatively(F=21.23, P<0.001). The vault was 665.32±184.03 μm at 1 d postoperatively, and continued to be significantly reduced at 1 wk, 1, 6 mo, and 1 a postoperatively compared with 1 d(F=52.10, P<0.001). However, it remained stable at 6 mo and 1 a postoperatively, and the difference was not statistically significant compared with vault at 1 mo postoperatively(P>0.05).CONCLUSION: ICL V4c has certain safety and efficiency in 1 a postoperative follow-up, and the parameters of the anterior segment of the eye stabilized in the early period.

Bibliometric analysis of aptamer-conjugated nanoparticles for diagnosis in the last two decades.

Objective.Aptamer-conjugated nanoparticles for diagnosis have recently gained increasing attention. Here, we performed a bibliometric analysis to provide an overview of this field over the past two decades.Methods. The terms 'aptamer, nanoparticles and diagnosis' were used to search for relevant original articles published in English from 2003 to 2022 in the Web of Science database. VOSviewer and CiteSpace software were employed to analyze the development process, knowledge structure, research hotspots, and potential trends in the field of aptamer-conjugated nanoparticles for diagnosis.Results. A total of 1076 original articles were retrieved, with a rapid increase in the annual output and citation. The journal 'Biosensors and Bioelectronics' has contributed the most in this field, and the most influential researcher, institution and country were Weihong Tan, the Chinese Academy of Sciences, China, respectively. Gold nanoparticles and quantum dots were the most used, but in the past three years, research hotspots focused on carbon dots and graphene quantum dots. Diagnostic directions primarily focused on cancer. The most used strategy was label-free electrochemical detection, but in the past two years, colorimetric analysis and fluorescence imaging emerged as hot topics.Conclusion.The bibliometric analysis reveals a rapid increase in the research on aptamer-conjugated nanoparticles for diagnosis, major contributors at the levels of journals, authors, institutions, and countries, and research preferences in diagnostic objects, nanoparticle types, and detection methods, as well as the evolution of research hotspots and future trends.

Relationship between prior statin therapy and radiological features and clinical outcomes of intracerebral hemorrhage.

OBJECTIVES: A post-hoc analysis of the ICH Deferoxamine (i-DEF) trial was performed to examine any associations pre-ICH statin use may have with ICH volume, PHE volume, and clinical outcomes. MATERIALS AND METHODS: Baseline characteristics were assessed. Various ICH and PHE parameters were measured via a quantitative, semi-automated method at baseline and follow-up CT scans 72-96 h later. A multivariable logistic regression model was created, adjusting for the variables that were significantly different on univariable analyses (p < 0.05), to assess any associations between pre-ICH statin use and measures of ICH and PHE, as well as good clinical outcome (mRS ≤2), at 90 and 180 days. RESULTS: 262 of 291 i-DEF participants had complete data available for analysis. 69 (26.3 %) used statins prior to ICH onset. Pre-ICH statin users had higher prevalences of hypertension, diabetes, and prior ischemic stroke; higher concomitant use of antihypertensives and antiplatelets; and higher blood glucose level at baseline. On univariable analyses, pre-ICH statin users had smaller baseline ICH volume and PHE volume on repeat scan, as well as smaller changes in relative PHE (rPHE) volume and edema extension distance (EED) between the baseline and repeat scans. In the multivariable analysis, none of the ICH and PHE measures or good clinical outcome was significantly associated with pre-ICH statin use. CONCLUSION: Pre-ICH statin use was not associated with measures of ICH or PHE, their growth, or clinical outcomes. These findings do not lend support to either overall protective or deleterious effects from statin use before or after ICH.

Data-driven decision-making for precision diagnosis of digestive diseases.

Modern omics technologies can generate massive amounts of biomedical data, providing unprecedented opportunities for individualized precision medicine. However, traditional statistical methods cannot effectively process and utilize such big data. To meet this new challenge, machine learning algorithms have been developed and applied rapidly in recent years, which are capable of reducing dimensionality, extracting features, organizing data and forming automatable data-driven clinical decision systems. Data-driven clinical decision-making have promising applications in precision medicine and has been studied in digestive diseases, including early diagnosis and screening, molecular typing, staging and stratification of digestive malignancies, as well as precise diagnosis of Crohn's disease, auxiliary diagnosis of imaging and endoscopy, differential diagnosis of cystic lesions, etiology discrimination of acute abdominal pain, stratification of upper gastrointestinal bleeding (UGIB), and real-time diagnosis of esophageal motility function, showing good application prospects. Herein, we reviewed the recent progress of data-driven clinical decision making in precision diagnosis of digestive diseases and discussed the limitations of data-driven decision making after a brief introduction of methods for data-driven decision making.

Differential diagnosis of hepatocellular carcinoma and intrahepatic cholangiocarcinoma based on spatial and channel attention mechanisms.

BACKGROUND: The pre-operative non-invasive differential diagnosis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) mainly depends on imaging. However, the accuracy of conventional imaging and radiomics methods in differentiating between the two carcinomas is unsatisfactory. In this study, we aimed to establish a novel deep learning model based on computed tomography (CT) images to provide an effective and non-invasive pre-operative differential diagnosis method for HCC and ICC. MATERIALS AND METHODS: We retrospectively investigated the CT images of 395 HCC patients and 99 ICC patients who were diagnosed based on pathological analysis. To differentiate between HCC and ICC we developed a deep learning model called CSAM-Net based on channel and spatial attention mechanisms. We compared the proposed CSAM-Net with conventional radiomic models such as conventional logistic regression, least absolute shrinkage and selection operator regression, support vector machine, and random forest models. RESULTS: With respect to differentiating between HCC and ICC, the CSAM-Net model showed area under the receiver operating characteristic curve (AUC) values of 0.987 (accuracy = 0.939), 0.969 (accuracy = 0.914), and 0.959 (accuracy = 0.912) for the training, validation, and test sets, respectively, which were significantly higher than those of the conventional radiomics models (0.736-0.913 [accuracy = 0.735-0.912], 0.602-0.828 [accuracy = 0.647-0.818], and 0.638-0.845 [accuracy = 0.618-0.849], respectively. The decision curve analysis showed a high net benefit of the CSAM-Net model, which suggests potential efficacy in differentiating between HCC and ICC in the diagnosis of liver cancers. CONCLUSIONS: The proposed CSAM-Net model based on channel and spatial attention mechanisms provides an effective and non-invasive tool for the differential diagnosis of HCC and ICC on CT images, and has potential applications in diagnosis of liver cancers.

An updated systematic review and meta-analysis investigating perihematomal edema and clinical outcome after intracerebral hemorrhage.

OBJECTIVES: The relationship between perihematomal edema (PHE) and intracerebral hemorrhage (ICH) outcomes is uncertain. Given newly published studies, we updated a previous systematic review and meta-analysis assessing the prognostic impact of PHE on ICH outcomes. MATERIALS AND METHODS: Databases were searched through September 2022 using pre-defined keywords. Included studies used regression to examine the association between PHE and functional outcome (assessed by modified Rankin Scale [mRS]) and mortality. The study quality was assessed using the Newcastle-Ottawa Scale. The overall pooled effect, and secondary analyses exploring different subgroups were obtained by entering the log transformed odds ratios and their confidence intervals into a DerSimonian-Laird random effects meta-analysis. RESULTS: Twenty-eight studies (n=8655) were included. The pooled effect size for overall outcome (mRS and mortality) was 1.05 (95% CI 1.03, 1.07; p<0.00). In secondary analyses, PHE volume and growth effect sizes were 1.03 (CI 1.01, 1.05) and 1.12 (CI 1.06, 1.19), respectively. Results of subgroup analyses assessing absolute PHE volume and growth at different time points were: baseline volume 1.02 (CI 0.98, 1.06), 72-hour volume 1.07 (CI 0.99, 1.16), growth at 24 hours 1.30 (CI 0.96, 1.74) and growth at 72 hours 1.10 (CI 1.04, 1.17). Heterogeneity across studies was substantial. CONCLUSIONS: This meta-analysis indicates that PHE growth, especially within the first 24 hours after ictus, has a stronger impact on functional outcome and mortality than PHE volume. Definitive conclusions are limited by the large variability of PHE measures, heterogeneity, and different evaluation time points between studies.

Analysis of aptamer-target binding and molecular mechanisms by thermofluorimetric analysis and molecular dynamics simulation.

Introduction: Aptamers are valuable for bioassays, but aptamer-target binding is susceptible to reaction conditions. In this study, we combined thermofluorimetric analysis (TFA) and molecular dynamics (MD) simulations to optimize aptamer-target binding, explore underlying mechanisms and select preferred aptamer. Methods: Alpha-fetoprotein (AFP) aptamer AP273 (as the model) was incubated with AFP under various experimental conditions, and melting curves were measured in a real-time PCR system to select the optimal binding conditions. The intermolecular interactions of AP273-AFP were analysed by MD simulations with these conditions to reveal the underlying mechanisms. A comparative study between AP273 and control aptamer AP-L3-4 was performed to validate the value of combined TFA and MD simulation in selecting preferred aptamers. Results: The optimal aptamer concentration and buffer system were easily determined from the dF/dT peak characteristics and the melting temperature (Tm) values on the melting curves of related TFA experiments, respectively. A high Tm value was found in TFA experiments performed in buffer systems with low metal ion strength. The molecular docking and MD simulation analyses revealed the underlying mechanisms of the TFA results, i.e., the binding force and stability of AP273 to AFP were affected by the number of binding sites, frequency and distance of hydrogen bonds, and binding free energies; these factors varied in different buffer and metal ion conditions. The comparative study showed that AP273 was superior to the homologous aptamer AP-L3-4. Conclusion: Combining TFA and MD simulation is efficient for optimizing the reaction conditions, exploring underlying mechanisms, and selecting aptamers in aptamer-target bioassays.

Combination of multiple nucleic acid aptamers for precision detection of tumors based on optical methods.

BACKGROUND AND PURPOSE: Nucleic acid aptamers are a novel molecular recognition tool that is functionally similar to antibodies but superior to antibodies in terms of thermal stability, structural modification, preparation, and cost, and therefore hold great promise for molecular detection. However, due to the limitations of a single aptamer in molecular detection, the multiple aptamer combination for bioanalysis has received much attention. Here, we reviewed the progress of tumor precision detection based on the combination of multiple nucleic acid aptamers and optical methods and discussed its challenges and prospects. METHODS: The relevant literature in PubMed was collected and reviewed. RESULTS: The combination of two or more aptamers with modern nanomaterials and analytical methods allows the fabrication of various detection systems for the simultaneous detection of different structural domains of a substance and/or different substances, including soluble tumor markers, tumor cell surface and intracellular markers, circulating tumor cells, and other tumor-related biomolecules, which has great potential for application in efficient and precise tumor detection. CONCLUSION: The combination of multiple nucleic acid aptamers provides a new approach for the precise detection of tumors and will play an important role in precision medicine for tumors.

Changes of HER2 low expression status in primary and recurrent/metastatic breast cancer / 中华病理学杂志

Objective: To investigate the evolution and clinical significance of HER2 low expression status in HER2 negative patients in primary and recurrent/metastatic breast cancers. Methods: The data and archived sections of 259 breast cancer patients with recurrence/metastasis and HER2-negative primary foci were collected from January 2015 to January 2022 at the Fourth Hospital of Hebei Medical University, and the HER2 status of primary and recurrence/metastasis foci was determined by immunohistochemistry (IHC), among which IHC 2+patients were subject to fluorescence in situ hybridization (FISH). The HER2 status was classified as HER2-0 group; patients with IHC 1+, IHC 2+and no FISH amplification were classified as HER2 low expression group; and patients with IHC 3+, IHC 2+and FISH amplified were classified as HER2-positive group. The changes of HER2 status in patients with HER2 low expression in primary versus recurrent/metastatic breast cancer foci were compared, and their clinicopathologic characteristics and prognosis were analyzed. Results: The overall concordance rate between primary and recurrent/metastatic HER2 status in breast cancer was 60.6% (157/259, κ=0.178). A total of 102 patients (102/259, 39.4%) had inconsistent primary and recurrent/metastatic HER2 status; 37 patients (37/259, 14.3%) had HER2-0 at the primary foci and HER2-low expression at the recurrent/metastatic; and 56 patients (56/259, 21.6%) had HER2-low expression in the primary foci and HER2-0 in the recurrent/metastatic. The recurrent/metastatic foci became low-expressing compared with the recurrent/metastatic foci which remained HER2-0 patients, with longer overall survival time, higher ER and PR positivity, lower Ki-67 positivity index, and lower tumor histological grade; all with statistically significant differences (all P<0.05). In the primary HER2-low group, patients with recurrent/metastatic foci became HER2-0 while those with recurrent/metastatic foci remained low expression; there were no statistically significant differences in clinicopathological features and overall survival time (all P>0.05). Conclusions: Unstable HER2 status in patients with HER2-0 and low expression in primary versus recurrent/metastatic breast cancer foci, and HER2-0 in the primary foci but low HER2 expression status in recurrence/metastasis is associated with favourable prognosis, and testing HER2 status in recurrence/metastasis can provide more treatment options for such patients.

Aggressive versus controlled fluid resuscitation in acute pancreatitis: A systematic review and meta-analysis of randomized controlled trials / 中华医学杂志(英文版)

BACKGROUND@#Early fluid resuscitation is one of the fundamental treatments for acute pancreatitis (AP), but there is no consensus on the optimal fluid rate. This systematic review and meta-analysis aimed to compare the efficacy and safety of aggressive vs. controlled fluid resuscitation (CFR) in AP.@*METHODS@#The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and Web of Science databases were searched up to September 30, 2022, for randomized controlled trials (RCTs) comparing aggressive with controlled rates of early fluid resuscitation in AP patients without organ failure on admission. The following keywords were used in the search strategy: "pancreatitis," "fluid therapy,""fluid resuscitation,"and "randomized controlled trial." There was no language restriction. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to assess the certainty of evidence. Trial sequential analysis (TSA) was used to control the risk of random errors and assess the conclusions.@*RESULTS@#A total of five RCTs, involving 481 participants, were included in this study. For primary outcomes, there was no significant difference in the development of severe AP (relative risk [RR]: 1.87, 95% confidence interval [CI] 0.95-3.68; P = 0.07; n = 437; moderate quality of evidence) or hypovolemia (RR: 0.98, 95% CI: 0.32-2.97; P = 0.97; n = 437; moderate quality of evidence) between the aggressive and CFR groups. A significantly higher risk of fluid overload (RR: 3.25, 95% CI: 1.53-6.93; P <0.01; n = 249; low quality of evidence) was observed in the aggressive fluid resuscitation (AFR) group than the controlled group. Additionally, the risk of intensive care unit admission ( P = 0.02) and the length of hospital stay ( P <0.01) as partial secondary outcomes were higher in the AFR group. TSA suggested that more studies were required to draw precise conclusions.@*CONCLUSION@#For AP patients without organ failure on admission, CFR may be superior to AFR with respect to both efficacy and safety outcomes.@*REGISTRATION@#PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; CRD 42022363945.

Clinical and genetic analysis of eight children with Primary hypertrophic cardiomyopathy / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and genetic characteristics of eight children with Primary hypertrophic cardiomyopathy (HCM).@*METHODS@#Eight children with HCM admitted to the Department of Cardiology of Henan Children's Hospital from January 2018 to December 2021 were selected as the study subjects. Clinical data of the children were collected. Whole exome sequencing was carried out on two children, and trio whole exome sequencing was carried out on the remainder 6 children. Sanger sequencing was used to verify the candidate variants in the children and their parents, and the pathogenicity of the variants was evaluated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).@*RESULTS@#The patients had included 5 males and 3 females, with their ages ranging from 5 to 13 years old. The average age of diagnosis was (7.87 ± 4.8) years old, and the cardiac phenotype showed non-obstructive HCM in all of the patients. WES has identified variants of the MYH7 gene in 4 children, including c.2155C>T (p.Arg719Trp), c.1208G>A (p.Arg403Gln), c.1358G>A (p.Arg453His), and c.1498G>A (p.Glu500Lys). Based on the guidelines from the ACMG, the first 3 variants were classified as pathogenic, while c.1498G>A (p.Glu500Lys) was classified as likely pathogenic (PM1+PM2_Supporting+PM6+PP3), which was also unreported previously. The remaining four children had all harbored maternal variants, including MYL2: c.173G>A (p.Arg58Gln; classified as pathogenic), TPM1: c.574G>A (p.Glu192Lys) and ACTC1: c.301G>A (p.Glu101Lys)(both were classified as likely pathogenic), and MYBPC3: c.146T>G (p.Ile49Ser; classified as variant of uncertain significance). Seven children were treated with 0.5 ~ 3 mg/(kg·d) propranolol, and their symptoms had improved significantly. They were followed up until September 30, 2022 without further cardiac event.@*CONCLUSION@#Genetic testing can clarify the molecular basis for unexplained cardiomyopathy and provide a basis for clinical diagnosis and genetic counseling. Discovery of the c.1498G>A (p.Glu500Lys) variant has also expanded the spectrum of MYH7 gene mutations underlying HCM.

New biopsy after antibiotic treatment: effect on outcomes of assisted reproduction in patients with infertility and chronic endometritis.

RESEARCH QUESTION: What is the effect of chronic endometritis on patients with infertility, the necessity of endometrial re-examination and the effect of improving chronic endometritis after one cycle of antibiotic treatment on pregnancy outcomes? DESIGN: Infertile patients (n = 4003) who underwent IVF and intracytoplasmic sperm injection treatment were included. Pregnancy outcomes of groups positive for chronic endometritis were compared with groups that were negative (group 1). Patients that were positive were divided into the chronic endometritis new biopsy group (group 2) and chronic endometritis non-re-examination group (group 3). After doxycycline treatment and re-examination, the chronic endometritis new biopsy group was divided into improved chronic endometritis group (ICE) and not-improved chronic endometritis group (NICE), and their general indicators and reproductive outcomes were compared. RESULTS: No significant difference was observed in embryo implantation, early or late pregnancy loss, ectopic pregnancy, clinical pregnancy and live birth rates between groups 2 and 3. The clinical pregnancy and live birth rates in the NICE group were significantly lower than those in the ICE group (P = 0.008 and P = 0.001, respectively). After controlling for potential confounding factors, age, average number of high-quality embryos, endometrial thickness on the day of embryo transfer and number and type of embryo transfer were factors associated with live birth rates. CONCLUSIONS: Endometrial re-examination of women with chronic endometritis treated with doxycycline had no effect on pregnancy outcomes. The first cycle of doxycycline treatment could effectively improve reproductive outcomes of women with five or more CD138+ cells/high-power field.

Impacts of Medical Security Level on Treatment Outcomes of Drug-Resistant Tuberculosis: Evidence from Wuhan City, China.

Background: Drug-resistant tuberculosis (DR-TB) is an increasingly serious global issue. DR-TB has a lower success rate and more severe interruption of treatment than ordinary tuberculosis. Incomplete treatment not only reduces recovery rate in DR-TB patients but also increases the spread of DR-TB. Optimizing medical security policies for DR-TB can reduce the economic burden of patients and can thereby improve treatment success rate. Methods: Patients with DR-TB who were registered in Wuhan Center for Tuberculosis Control and Prevention from January 2016 to December 2019 were selected as research subjects. General descriptive statistical analysis methods were used in analyzing patients' treatment outcomes and medical security compensation rate. The binary logistic regression was used in analyzing the impacts of medical security level on treatment outcomes of DR-TB. Results: A total of 409 DR-TB patients were included in the study, and the refusal rate was 12.47%. The treatment success rate was only 37.09% for patients who started treatment and had treatment outcomes. The total out-of-pocket expenses (OOPs) per capita for DR-TB patients were 13,005.61 Chinese yuan. The outpatient effective compensation ratio (ECR) of DR-TB patients was only 51.04%. The outpatient ECR of DR-TB with subsidies of public health projects (SPHPs) were nearly 80% higher than those without SPHP. high outpatient ECR helped optimize treatment outcomes (P < 0.001, OR = 1.038). The inpatient ECR had no effect on patients' treatment outcomes (P = 0.158, OR = 0.986). Conclusion: Many DR-TB patients did not receive complete treatment. The key breakthrough point in improving DR-TB treatment outcomes is to optimize the outpatient medical insurance compensation policy. Including the costs of DR-TB in expenses for severe diseases in outpatient care is recommended, and financial investment should be appropriately increased to ensure the high coverage ratio of subsidies for public health projects.

New indexes derived from routine blood tests and their clinical application in hepatocellular carcinoma.

Considerable efforts have been made in the diagnosis and treatment of hepatocellular carcinoma (HCC), but the prognosis of patients with HCC remains poor. The development of officious and easy-to-use indicators that are applicable to all levels of hospitals for the diagnosis, prognosis and risk prediction of HCC may play an important role in improving the current undesirable situation. The occurrence of HCC can cause a series of local and systemic changes, involving liver function, inflammation, immunity, and nutrition, which can be reflected in routine clinical indicators, especially laboratory metrics. A comprehensive analysis of these routine indicators is capable of providing important information for the clinical management of HCC. Routine clinical indicators are daily medical data that are readily available, easily repeatable, and highly acceptable, which has attracted clinicians to derive a number of comprehensive indexes from routine clinical indicators by means of four arithmetic operations, scoring system, and mathematical modeling. These indexes integrate several clinical indicators into a new single indicator that performs better than any of original individual indicators in the risk prediction, clinical diagnosis and prognostic evaluation of HCC and is easy to use. Herein, we reviewed recent indexes derived from routine clinical indicators for the diagnosis, prognosis and risk prediction of HCC.

The Prognostic Roles of Perihematomal Edema and Ventricular Size in Patients with Intracerebral Hemorrhage.

BACKGROUND: Conflicting data exist regarding the association of perihematomal edema (PHE) with outcomes after intracerebral hemorrhage (ICH). We performed a post hoc analysis of the ICH Deferoxamine trial to examine whether an early change in ventricular size (VS), as a composite measure of PHE growth and mass effect, intraventricular hemorrhage, and hydrocephalus, is a more accurate predictor of outcome than PHE measures alone. METHODS: Computerized tomography scans were performed at baseline and after 72-96 h. We evaluated measures of PHE and change in VS as predictors of outcome, assessed by a dichotomized modified Rankin Scale score (0-2 versus 3-6), primarily at 90 days and secondarily at 30 days. A multivariable logistic regression model was fitted for each predictor, with adjustment for the same confounders. RESULTS: A total of 248 participants were included after we excluded those requiring external ventricular drains. On univariate analyses, older age, female sex, lower Glasgow Coma Scale score and baseline temperature, greater ICH volume, absolute PHE volume, edema extension distance at presentation, lesser changes in relative PHE volume and edema extension distance, and an increase in VS were associated with poor outcome. In multivariable analyses, only the increase in VS was associated with lower odds of modified Rankin Scale scores 0-2 at 90 days (odds ratio 0.927, 95% confidence interval 0.866-0.970, p = 0.001) and 30 days (odds ratio 0.931, 95% confidence interval 0.888-0.975, p = 0.003). CONCLUSIONS: Within the context of a randomized controlled trial with standardized imaging and functional assessments, we did not find significant associations between measures of PHE and outcome but documented an independent association between early increase in VS and lower odds of good clinical outcome.

Aptamer-Based Triple Serum Fluorescence Intensity Assay: A Novel and Feasible Method for the Clinical Diagnosis of Primary Hepatic Carcinoma.

Background and Aims: Aptamers are artificial ligands that bind to biological targets with high specificity and affinity. We previously selected a group of aptamers against the serum of primary hepatic carcinoma (PHC) via systematic evolution of ligands by exponential and enrichment (SELEX) method, and some of the aptamers were valuable for PHC diagnosis in polyacrylamide gel electrophoresis (PAGE) analysis. Here, we used aptamers to develop a novel method suitable for the clinical diagnosis of PHC. Methods: The intensities of serum autofluorescence, cell-free DNA (cfDNA)-related fluorescence and aptamer-related fluorescence, named the aptamer-based triple serum fluorescence intensity (ATSFI), were sequentially measured at 8 °C and 37 °C in one tube by using a real-time polymerase chain reaction (PCR) system as a fluorimeter in patients with PHC (n=346) or liver cirrhosis (n=321). The diagnostic performances of ATSFI indicators alone and in combination were evaluated by area under the receiver operator characteristic curve (AUROC), and the underlying clinical mechanisms were analyzed by bivariate correlation. Results: The measurement of ATSFI was high throughput, rapid, convenient, and low cost. The aptamer-related fluorescence indicator SEA-SE37 was the most valuable for PHC diagnosis among all fluorescence indicators and superior to alpha-fetoprotein (AFP) (AUROC 0.879 vs. 0.836). The logistic model of ATSFI indicators exhibited excellent diagnostic performance for PHC, including AFP-negative, early and small PHCs, with AUROCs of 0.935-0.950 and accuracies of 86.8-88.3%. The diagnostic performance was further improved when ATSFI indicators were combined with AFP, with AUROCs of approximately 0.95 and accuracies of approximately 90%, suggesting ATSFI was independent of but complementary to AFP in PHC diagnosis. ATSFI models were highly valuable in clinical decision-making. The aptamer-related fluorescence intensity was generally independent of the clinicopathological characteristics of PHC but correlated with laboratory characteristics of PHC serum. Conclusions: The ATSFI assay is a novel, robust and feasible method for the clinical diagnosis of PHC.