Association Between Serine Concentration and Coronary Heart Disease: A Case-Control Study.

Purpose: Early identification of new residual risk factors for coronary heart disease (CHD) is warranted. In this study, we aim to investigate the association between the serine concentration, an important amino acid in one-carbon metabolism, and CHD in Chinese hospitalized patients. Patients and Methods: This case-control study included 428 case-control pairs comprising patients with CHD with a maximum coronary artery stenosis degree of >70% and controls with stenosis of <30%. The individuals were matched by age, sex, and date of coronary angiography at Peking University First Hospital from January 1, 2016, to December 31, 2019. Conditional logistic regression was used to investigate the associations between the serine concentration and CHD. Results: Patients with CHD were aged 63.48 ± 10.38 years, and 43.73% were male. Compared with controls, patients with CHD had a slightly lower serine concentration (13.35 ± 4.20 vs 13.77 ± 4.08 µg/mL), but the difference was not significant. In the multivariable conditional logistic regression analysis, for every 1 µg/mL increase in serine concentration, the odds of CHD decreased by 6% (95% confidence interval [CI] 0.90-0.99; P = 0.010). Patients with a serine concentration of ≥13.41 µg/mL had a lower CHD risk than those with a serine concentration of <13.41 µg/mL (odds ratio [OR] 0.57, 95% CI 0.39-0.84; P = 0.004). Subgroup analyses showed that sex interacted with the relationship between serine concentration and CHD (P interaction = 0.039), which was more significant in males (OR 0.93, 95% CI 0.87-0.98; P = 0.013) than in females. Conclusion: This study observed an inverse association between the serine concentration and CHD prevalence in Chinese hospitalized patients, which revealed that serine might play a protective role in CHD.

Analysis of molecular epidemiological characteristics and antimicrobial susceptibility of vancomycin-resistant and linezolid-resistant Enterococcus in China.

BACKGROUND: This study investigates the distribution and characteristics of linezolid and vancomycin susceptibilities among Enterococcus faecalis (E. faecalis) and Enterococcus faecium (E. faecium) and explores the underlying resistance mechanisms. METHODS: A total of 2842 Enterococcus clinical isolates from patients were retrospectively collected, and their clinical data were further analyzed. The minimum inhibitory concentrations (MICs) of vancomycin and linezolid were validated by broth dilution method. The resistance genes optrA, cfr, vanA, vanB and vanM were investigated using polymerase chain reaction (PCR). Housekeeping genes and resistance genes were obtianed through whole-genome sequencing (WGS). RESULTS: Of the 2842 Enterococcus isolates, 88.5% (2516) originated from urine, with E. faecium accounted for 60.1% of these. The vanA gene was identified in 27/28 vancomycin resistant Enterococcus (VRE) isolates, 4 of which carried both vanA and vanM genes. The remaining strain was vanM positive. The optrA gene was identified in all E. faecalis isolates among linezolid resistant Enterococcus (LRE). E. faecium showed a higher multiple antibiotic resistance index (MAR index) compared to E. faecalis. The multi-locus sequence typing (MLST) showed the sequence type of E. faecium mainly belongs to clonal complex (CC) 17, nearly E. faecalis isolates analyzed were differentiated into 7 characteristics of sequence types (STs), among which ST16 of CC16 were the major lineage. CONCLUSION: Urine was the primary source of VRE and LRE isolates in this study. E. faecium showed higher levels of resistance compared to E. faecalis. OptrA gene was detected in 91.6% of LRE, which could explain linezolid resistance, and van genes were detected in all vancomycin resistant Enterococcus strains, while vanA was a key resistance mechanism in VRE identified in this study.

The application of nanomaterials in tumor therapy based on the regulation of mechanical properties.

Mechanical properties, as crucial physical properties, have a significant impact on the occurrence, development, and metastasis of tumors. Regulating the mechanical properties of tumors to enhance their sensitivity to radiotherapy and chemotherapy has become an important strategy in the field of cancer treatment. Over the past few decades, nanomaterials have made remarkable progress in cancer therapy, either based on their intrinsic properties or as drug delivery carriers. However, the investigation of nanomaterials of mechanical regulation in tumor therapy is currently in its initial stages. The mechanical properties of nanomaterials themselves, drug carrier targeting, and regulation of the mechanical environment of tumor tissue have far-reaching effects on the efficient uptake of drugs and clinical tumor treatment. Therefore, this review aims to comprehensively summarize the applications and research progress of nanomaterials in tumor therapy based on the regulation of mechanical properties, in order to provide strong support for further research and the development of treatment strategies in this field.

Weakly Supervised Pose Estimation of Surgical Instrument from a Single Endoscopic Image.

Instrument pose estimation is a key demand in computer-aided surgery, and its main challenges lie in two aspects: Firstly, the difficulty of obtaining stable corresponding image feature points due to the instruments' high refraction and complicated background, and secondly, the lack of labeled pose data. This study aims to tackle the pose estimation problem of surgical instruments in the current endoscope system using a single endoscopic image. More specifically, a weakly supervised method based on the instrument's image segmentation contour is proposed, with the effective assistance of synthesized endoscopic images. Our method consists of the following three modules: a segmentation module to automatically detect the instrument in the input image, followed by a point inference module to predict the image locations of the implicit feature points of the instrument, and a point back-propagatable Perspective-n-Point module to estimate the pose from the tentative 2D-3D corresponding points. To alleviate the over-reliance on point correspondence accuracy, the local errors of feature point matching and the global inconsistency of the corresponding contours are simultaneously minimized. Our proposed method is validated with both real and synthetic images in comparison with the current state-of-the-art methods.

Insertion sequence transposition activates antimycobacteriophage immunity through an lsr2-silenced lipid metabolism gene island.

Insertion sequences (ISs) exist widely in bacterial genomes, but their roles in the evolution of bacterial antiphage defense remain to be clarified. Here, we report that, under the pressure of phage infection, the IS1096 transposition of Mycobacterium smegmatis into the lsr2 gene can occur at high frequencies, which endows the mutant mycobacterium with a broad-spectrum antiphage ability. Lsr2 functions as a negative regulator and directly silences expression of a gene island composed of 11 lipid metabolism-related genes. The complete or partial loss of the gene island leads to a significant decrease of bacteriophage adsorption to the mycobacterium, thus defending against phage infection. Strikingly, a phage that has evolved mutations in two tail-filament genes can re-escape from the lsr2 inactivation-triggered host defense. This study uncovered a new signaling pathway for activating antimycobacteriophage immunity by IS transposition and provided insight into the natural evolution of bacterial antiphage defense.

Exendin-4 blockade of T1R2/T1R3 activation improves Pseudomonas aeruginosa-related pneumonia in an animal model of chemically induced diabetes.

OBJECTIVE: Poorly controlled diabetes frequently exacerbates lung infection, thereby complicating treatment strategies. Recent studies have shown that exendin-4 exhibits not only hypoglycemic but also anti-inflammatory properties. This study aimed to explore the role of exendin-4 in lung infection with diabetes, as well as its association with NOD1/NF-κB and the T1R2/T1R3 sweet taste receptor. METHODS: 16HBE human bronchial epithelial cells cultured with 20 mM glucose were stimulated with lipopolysaccharide (LPS) isolated from Pseudomonas aeruginosa (PA). Furthermore, Sprague‒Dawley rats were fed a high-fat diet, followed by intraperitoneal injection of streptozotocin and intratracheal instillation of PA. The levels of TNF-α, IL-1ß and IL-6 were evaluated using ELISAs and RT‒qPCR. The expression of T1R2, T1R3, NOD1 and NF-κB p65 was assayed using western blotting and immunofluorescence staining. Pathological changes in the lungs of the rats were observed using hematoxylin and eosin (H&E) staining. RESULTS: At the same dose of LPS, the 20 mM glucose group produced more proinflammatory cytokines (TNF-α, IL-1ß and IL-6) and had higher levels of T1R2, T1R3, NOD1 and NF-κB p65 than the normal control group (with 5.6 mM glucose). However, preintervention with exendin-4 significantly reduced the levels of the aforementioned proinflammatory cytokines and signaling molecules. Similarly, diabetic rats infected with PA exhibited increased levels of proinflammatory cytokines in their lungs and increased expression of T1R2, T1R3, NOD1 and NF-κB p65, and these effects were reversed by exendin-4. CONCLUSIONS: Diabetic hyperglycemia can exacerbate inflammation during lung infection, promote the increase in NOD1/NF-κB, and promote T1R2/T1R3. Exendin-4 can ameliorate PA-related pneumonia with diabetes and overexpression of NOD1/NF-κB. Additionally, exendin-4 suppresses T1R2/T1R3, potentially through its hypoglycemic effect or through a direct mechanism. The correlation between heightened expression of T1R2/T1R3 and an intensified inflammatory response in lung infection with diabetes requires further investigation.

Electrochemiluminescence quenching effect of Cu2O towards flower-like ferric ion-doped g-C3N4 and its application for Cyfra21-1 immunosensing.

In this article, ferric ion-doped floral graphite carbon nitride (Fe-CN-3, energy donor) was used to construct the substrate of the immunosensor and copper oxide nanocubes (Cu2O, energy acceptor) were taken as an efficient ECL quenching probe. A sandwich quench electrochemiluminescence (ECL) immunosensor for soluble cytokeratin 19 fragment (Cyfra21-1) detection was preliminarily developed based on a novel resonant energy transfer donor-acceptor pair. Fe-CN-3, a carbon nitride that combines the advantages of metal ion doping as well as morphology modulation, is used in ECL luminophores to provide more excellent ECL performance, which makes a significant contribution to the application and development of carbon nitride in the field of ECL biosensors. The regular shape, high specific surface area and excellent biocompatibility of the quencher Cu2O nanocubes facilitate the labeling of secondary antibodies and the construction of sensors. Meanwhile, as an energy acceptor, the UV absorption spectrum of Cu2O can overlap efficiently with the energy donor's ECL emission spectrum, making it prone to the occurrence of ECL-RET and thus obtaining an excellent quenching effect. These merits of the donor-acceptor pair enable the sensor to have a wide detection range of 0.00005-100 ng/mL and a low detection limit of 17.4 fg/mL (S/N = 3), which provides a new approach and theoretical basis for the clinical detection of lung cancer.

Association of plasma homocysteine with peripheral arterial disease in the hypertensive adults: A cross-sectional study.

Increased plasma homocysteine (Hcy) has been identified as one of the important risk factors for cardiovascular disease. However, the association between plasma Hcy and peripheral artery disease (PAD) is still controversial. This study aimed to investigate the association between plasma Hcy and PAD and the potential modifier factors in Chinese hypertensive adults. A total of 25 300 hypertensive patients aged 18 years or older were included in the analysis in this cross-sectional study. The outcome was PAD, which defined as an ankle-brachial index ≤0.90 in either limb. Multiple logistic regression was used to analyze the relationship between plasma Hcy and PAD. The median plasma Hcy was 14.00 (interquartile range: 11.60-17.80) µmol/L. There was a significant positive association between plasma Hcy and PAD (per SD increment; OR: 1.13; 95% CI: 1.06-1.19). Patients in the upper plasma Hcy tertile (≥16.16 µmol/L) were associated with a 53% increased risk of PAD compared with patients in the lower tertile (<12.33 µmol/L) after adjustment for multiple potential confounders. Subgroup analyses showed the association between Hcy and PAD was robust among various strata. Among Chinese adults with hypertension, plasma Hcy is an independent risk factor for PAD. This finding may improve the risk stratification of PAD.

Lsr2 acts as a cyclic di-GMP receptor that promotes keto-mycolic acid synthesis and biofilm formation in mycobacteria.

Cyclic di-GMP (c-di-GMP) is a second messenger that promotes biofilm formation in several bacterial species, but the mechanisms are often unclear. Here, we report that c-di-GMP promotes biofilm formation in mycobacteria in a manner dependent on the nucleoid-associated protein Lsr2. We show that c-di-GMP specifically binds to Lsr2 at a ratio of 1:1. Lsr2 upregulates the expression of HadD, a (3R)-hydroxyacyl-ACP dehydratase, thus promoting the synthesis of keto-mycolic acid and biofilm formation. Thus, Lsr2 acts as a c-di-GMP receptor that links the second messenger's function to lipid synthesis and biofilm formation in mycobacteria.

A potential therapeutic approach for gastric cancer: inhibition of LACTB transcript 1.

BACKGROUND: This study sought to investigate the role of LACTB transcript 1 in regulating adaptive immune resistance and stemness in gastric cancer and its potential as a therapeutic target for precision medicine. METHODS: Bioinformatics analysis and RT-qPCR were used to analyze the expression level of LACTB and its transcripts in gastric cancer cells. The effects of LACTB transcript 1 on adaptive immune resistance and stemness were evaluated using in vitro cell experiments and western blotting experiments. RESULTS: Our study findings revealed that LACTB transcript 1 modulated adaptive immune resistance and inhibited the stemness of gastric cancer cells. Knocking down the expression level of LACTB transcript 1 activated autophagy and inhibited EMT. As expected, overexpression of LACTB transcript 1 yielded the opposite findings. The expression level of LACTB transcript 1 in the peripheral blood of gastric cancer patients was consistent with the bioinformatics analysis, suggesting its potential as a biomarker of gastric cancer. CONCLUSIONS: LACTB transcript 1 is a promising therapeutic target for precision medicine in gastric cancer by modulating immune evasion mechanisms and stemness. These findings provide insights into leveraging long non-coding RNAs (lncRNAs) in immunotherapy, radiotherapy, and chemotherapy to enhance cancer therapy efficacy, particularly in the context of targeting tumor heterogeneity and stemness.

Budesonide/formoterol maintenance and reliever therapy in childhood asthma: Real-world effectiveness and economic assessment.

INTRODUCTION: The study aims to compare the real-world effectiveness and economy of the budesonide/formoterol reliever and maintenance therapy (SMART) with fixed-dose inhaled corticosteroids (ICS)/long-acting b-agonist (LABA) or ICS alone plus as-needed, short-acting ß2 agonists (SABA) in pediatric patients. METHODS: The outpatient data warehouse of a hospital in China was used. A total of 103 patients under 18 years old in the SMART group and 63 patients in the control group were included from January 1, 2020 to December 31, 2021. The effectiveness was assessed using asthma attacks and lung function at baseline, 6 months and 12 months follow-up. Cost-effectiveness analysis was performed with a three-state Markov model from the healthcare system perspective. One-way sensitivity analyses and probabilistic sensitivity analyses were performed to check the robustness of the results. RESULTS: The SMART regimen was more effective than other strategies in reducing the risk of mild and severe attacks in the real-life management of childhood asthma. Patients in both groups showed significant improvement in lung function at 6 and 12 months in contrast to baseline. Compared with other strategies, the forced expiratory volume in 1 s (FEV1 ) level in the SMART group was markedly improved at 6 months. The total cost of outpatient service using the SMART regimen was lower than that of other strategies, while the drug costs were similar in different groups. Incremental cost-effectiveness analysis results showed that using the SMART regimen reduced the total cost by approximately CNY 10,516.11 per year with a 0.12 quality-adjusted life year (QALYs) increase. Sensitive analyses supported that the SMART regimen was the dominant choice at the willingness-to-pay threshold of CNY 85,698, per capita GDP in China. CONCLUSIONS: Collectively, our findings indicate that the real-world effectiveness and economy of the SMART regimen are superior to the traditional strategies in pediatric asthma patients.

IS26 mediated blaCTX-M-65 amplification in Escherichia coli increase the antibiotic resistance to cephalosporin in vivo.

OBJECTIVES: To characterize two Escherichia coli strains isolated from a patient pre- and post-treatment, using ß-lactams and ß-lactam/ß-lactamase inhibitor combinations (BLBLIs). METHODS: A combination of antibiotic susceptibility testing (AST) with whole genome sequencing using Illumina and Oxford Nanopore platforms. Long-read sequencing and reverse transcription-quantitative PCR were performed to determine the copy numbers and expression levels of antibiotic resistance genes (ARGs), respectively. Effect on fitness costs were assessed by growth rate determination. RESULTS: The strain obtained from the patient after the antibiotic treatment (XH989) exhibited higher resistance to cefepime, BLBLIs and quinolones compared with the pre-treatment strain (XH987). Sequencing revealed IS26-mediated duplications of a IS26-fosA3-blaCTX-M-65 plasmid-embedded element in strain XH989. Long-read sequencing (7.4 G data volume) indicated a variation in copy numbers of blaCTX-M-65 within one single culture of strain XH989. Increased copy numbers of the IS26-fosA3-blaCTX-M-65 element were correlated with higher CTX-M-65 expression level and did not impose fitness costs, while facilitating faster growth under high antibiotic concentrations. CONCLUSION: Our study is an example from the clinic how BLBLIs and ß-lactams exposure in vivo possibly promoted the amplification of an IS26-multiple drug resistance (MDR) region. The observation of a copy number variation seen with the blaCTX-M-65 gene in the plasmid of the post-treatment strain expands our knowledge of insertion sequence dynamics and evolution during treatment.

Fetal echocardiography changes of the right ventricle of well-controlled gestational diabetes mellitus.

BACKGROUND: There is few evidence of right ventricular (RV) function in fetuses with gestational diabetes mellitus (GDM). Therefore, the aim of this study was to assess the RV function of fetuses using routine and two-dimensional speckle-tracking echocardiography (2D STE) to determine the effects of well-controlled GDM in the third trimester. METHODS: We used a Philips Epiq7C ultrasound instrument to obtain RV data sets from 63 subjects from July 2019 to February 2022. We compared the free wall thickness (FWT), fractional area change (FAC), Tei index (TEI), tricuspid annular plane systolic excursion (TAPSE) and free wall longitudinal strain(FWLS)of the RV in mothers with well-controlled GDM and normal gestational age-matched fetuses. RESULTS: 63 third trimester fetuses (32 GDM; 31 healthy controls) met the enrolment criteria. Significant differences in fetal RV were detected between the GDM and control groups for the FAC (36.35 ± 6.19 vs. 41.59 ± 9.11; P = 0.008) and the FWLS (-18.28 ± 4.23 vs. -20.98 ± 5.49; P = 0.021). There was a significant difference among the segmental strains of the base, middle and apex of the RV free wall in the healthy controls (P = 0.003), but in the GDM group, there was no statistical difference (p = 0.076). RV FWLS had a strong correlation with FAC (r = 0.467; P = 0.0002). CONCLUSIONS: In well-controlled GDM, there was measurable fetal RV hypertrophy and significant systolic function decline, indicating the presence of ventricular remodeling and dysfunction. 2D-STE can evaluate the RV free wall contraction in a more comprehensive way.

Fine particulate matter promotes airway inflammation and mucin production by activating endoplasmic reticulum stress and the IRE1α/NOD1/NF­κB pathway.

Fine particulate matter (PM2.5) is a type of small particle that is <2.5 µm in diameter that may cause airway inflammation. Thus, the present study aimed to explore the effects of PM2.5 on endoplasmic reticulum (ER) stress and airway inflammation in human airway epithelial cells. For this purpose, HBE135­E6E7 airway epithelial cells were cultured and exposed to specific concentrations of PM2.5 for various periods of time, and cell viability was determined using a Cell Counting Kit­8 assay. The results of the present study demonstrated that exposure to PM2.5 increased the mRNA and protein expression levels of interleukin (IL)­6, tumor necrosis factor (TNF)­α and mucin 5AC (MUC5AC). Moreover, the expression levels of ER stress­related proteins, such as glucose­regulated protein 78, CCAAT­enhancer binding protein homologous protein, activating transcription factor 6, protein kinase R­like ER kinase (PERK), phosphorylated (p­)PERK, inositol­requiring enzyme 1α (IRE1α) and p­IRE1α, and nucleotide­binding oligomerization domain 1 (NOD1) expression levels were increased following exposure to PM2.5. Transfection with IRE1α small interfering RNA (siRNA) led to the increased production of IL­6, TNF­α and MUC5AC. Moreover, the expression of NOD1 and the translocation of NF­κB p65 were inhibited following transfection with IRE1α siRNA. In addition, the results of the present study demonstrated that transfection with NOD1 siRNA decreased the production of IL­6, TNF­α and MUC5AC, and decreased the translocation of NF­κB p65. The expression levels of IL­6, TNF­α and MUC5AC were increased in the HBE135­E6E7 cells following treatment with C12­iE­DAP, a NOD1 agonist. Moreover, treatment with C12­iE­DAP led to the activation of NF­κB p65. Collectively, the results of the present study suggest that PM2.5 promotes airway inflammation and mucin production by activating ER stress in HBE135­E6E7 airway epithelial cells, and that the IRE1α/NOD1/NF­κB pathway may be involved in this process.

A CaCO3-based nanoplatform with sonodynamic and tumor microenvironment activated for combined in vitro cancer therapy.

INTRODUCTION: Sonodynamic therapy (SDT) has potential clinical applications for cancer therapy, and is yet restricted by complex tumor microenvironmental (TME) factors. Thus, the research problem of TME modulation as well as efficient tumor treatment still needs to be clarified. METHOD: In this study, a calcium carbonate (CaCO3) nanoplatform was designed for ultrasound (US) and TME response-triggered, which encapsulated Ag2S and loaded with l-Arg, and further wrapped with RBC/Platelet membrane, named as QD@Ca/ML-Arg. RESULTS: Non-invasive US-triggered SDT by Ag2S and acidic environment-responsive drug release were achieved. In vitro experiments validated the efficacy of SDT, Ca-ion interference and nitric oxide (NO) gas therapy as combined therapy for cancer treatment. By means of RNA sequencing, the cancer therapeutic mechanism of SDT in redox-related pathways was elucidated. The immunosuppressive TME was simulated with a M2-macrophage/cancer cell co-culture system to confirm the immune activating effect of immunogenic cell death (ICD). CONCLUSION: Accordingly, the potential of QD@Ca/ML-Arg-was demonstrated for in vitro TME modulation, cancer therapeutic efficacy and clinical translation.

Identification of high-level ceftriaxone-resistant Neisseria gonorrhoeae isolates with diverse penA alleles in Zhejiang, China.

OBJECTIVES: The prevalence of ceftriaxone-resistant Neisseria gonorrhoeae poses a significant threat to the effectiveness of gonorrhoea treatment. The aim of the present study was to analyse the characteristics of ceftriaxone-resistant N. gonorrhoeae, with a specific focus on high-level ceftriaxone-resistant strains. METHODS: A total of 207 strains of N. gonorrhoeae were collected from hospitals in Zhejiang, China, between 2019 and 2020. From this collection, we selected 8 strains of ceftriaxone-resistant N. gonorrhoeae for whole-genome sequencing, genotyping, and molecular profile analysis. For clonal strains (FC428-like), we conducted a phylogenetic analysis to understand their origin and evolutionary path. RESULTS: Among the selected strains, 5 demonstrated high-level ceftriaxone resistance (MIC 1-2 mg/L). The genotyping results showed that these isolates had a higher diversity of penA alleles than expected. Four isolates had mosaic penA-60.001 allele and the remaining four had different non-mosaic penA alleles. Phylogenetic analysis suggested that the emergence of FC428-like clones containing penA-60.001 may result from further dissemination of different FC428 subclones from different regions of China. The identification of high-level ceftriaxone resistance in non-mosaic penA gonococci, specifically in the ZJ20-3 isolate (penA-21.001) with an MIC of 2 mg/L, is a groundbreaking discovery. CONCLUSIONS: We present a comprehensive analysis of ceftriaxone-resistant N. gonorrhoeae isolates in Zhejiang, highlighting a significant diversity of penA alleles. The identification of strains exhibiting resistance to ceftriaxone at high levels in our study underscores the potential threat to existing protocols for gonorrhoea treatment. Consequently, we strongly emphasize the urgent need to enhance surveillance initiatives focused on ceftriaxone-resistant N. gonorrhoeae.

Mycobacterial phage TM4 requires a eukaryotic-like Ser/Thr protein kinase to silence and escape anti-phage immunity.

In eukaryotic cells, serine/threonine protein kinases (StpKs) play important roles in limiting viral infections. StpKs are commonly activated upon infections, inhibiting the expression of genes central for viral replication. Here, we report that a eukaryotic-like StpK7 encoded by MSMEG_1200 in M. smegmatis is required for mycobacteriophage TM4 to escape bacterial defense. stpK7 is located within a gene island, MSMEG_1191-MSMEG_1200, containing multiple anti-phage genes resembling the BREX (bacteriophage exclusion) phage-resistance system. StpK7 negatively regulates the expression of this gene island. Following phage TM4 infection, StpK7 is induced, directly phosphorylating the transcriptional regulator MSMEG_1198 and inhibiting its positive regulatory activity, thus reducing the expression of multiple downstream genes in the BREX-like gene island. Further analysis showed that genes within this anti-phage island critically regulate mycobacterial lipid hemostasis and phage adsorption. Collectively, this work characterizes a regulatory network driven by StpK7, which is utilized by phage TM4 to escape from the host defense against mycobacteria.

From WSI-level to patch-level: Structure prior-guided binuclear cell fine-grained detection.

Accurate and quick binuclear cell (BC) detection plays a significant role in predicting the risk of leukemia and other malignant tumors. However, manual counting of BCs using microscope images is time consuming and subjective. Moreover, traditional image processing approaches perform poorly due to the limitations in staining quality and the diversity of morphological features in binuclear cell (BC) microscopy whole-slide images (WSIs). To overcome this challenge, we propose a multi-task method inspired by the structure prior of BCs based on deep learning, which cascades to implement BC coarse detection at the WSI level and fine-grained classification at the patch level. The coarse detection network is a multitask detection framework based on circular bounding boxes for cell detection and central key points for nucleus detection. Circle representation reduces the degrees of freedom, mitigates the effect of surrounding impurities compared to usual rectangular boxes and can be rotation invariant in WSIs. Detecting key points in the nucleus can assist in network perception and be used for unsupervised color layer segmentation in later fine-grained classification. The fine classification network consists of a background region suppression module based on color layer mask supervision and a key region selection module based on a transformer due to its global modeling capability. Additionally, an unsupervised and unpaired cytoplasm generator network is first proposed to expand the long-tailed distribution dataset. Finally, experiments are performed on BC multicenter datasets. The proposed BC fine detection method outperforms other benchmarks in almost all evaluation criteria, providing clarification and support for tasks such as cancer screenings.

Combined use of amlodipine and folic acid are significantly more efficacious than amlodipine alone in lowering plasma homocysteine and blood pressure among hypertensive patients with hyperhomocysteinemia and intolerance to ACEI: A multicenter, randomized, double-blind, parallel-controlled clinical trial.

Hyperhomocysteinemia with hypertension can synergistically increase the risk of stroke. The China stroke primary prevention trial showed that combining 0.8 mg folic acid (FA) with angiotensin-converting enzyme inhibitor (ACEI) can effectively lower plasma total homocysteine (tHcy) and blood pressure (BP); and reduce first stroke risk by additional 21% compared to ACEI alone. However, intolerance to ACEI is common in Asians and amlodipine can be alternative. This is a multicenter, randomized, double-blind, parallel-controlled clinical trial (RCT) which evaluated whether amlodipine combined with FA is more efficacious than amlodipine alone in lowering tHcy and BP among Chinese hypertensive with hyperhomocysteinemia and intolerance to ACEI. 351 Eligible patients were randomly assigned by 1:1:1 ratio to receive amlodipine-FA tablet daily (amlodipine 5 mg/FA 0.4 mg, A group); amlodipine 5 mg/FA 0.8 mg tablet daily (B group); amlodipine 5 mg daily (C group, control group). Follow-up was conducted at 2, 4, 6, and 8 weeks. The primary outcome was efficacy of lowering both tHcy and BP at the end of 8-week treatment. Compared with C group, A group had a significantly higher rate of lowering both tHcy and BP (23.3% vs. 6.0%; Odds Ratio [OR], 8.68; 95% CI, 3.04-24.78, P < .001); B group also had a higher rate of lowering both tHcy and BP (20.3% vs. 6.0%; OR: 5.90; 95% CI, 2.11-16.47, P < .001). This RCT showed amlodipine combined with FA compared with amlodipine alone, each had significantly higher efficacy of lowering both tHcy and BP. No difference was found in BP-lowering and occurrence of adverse events between the three groups.

Spatiotemporal Epidemiology of the Gonorrhea Epidemic in Relation to Neighborhood-level Structural Factors in an Eastern Province of China, 2016-2020.

Context: Gonorrhea, a highly communicable, sexually transmitted infection, remains a major public-health concern globally. In recent years, Zhejiang province, an eastern province, has had the highest incidence of gonorrhea in China. Objective: The study intended to identify the geographic distribution patterns and spaciotemporal clustering characteristics of the disease's incidence in Zhejiang between 2016 and 2020, to understand the spatial epidemiology of gonorrhea and to pinpoint the locations with relatively high risks of gonorrhea, the hotspots, which could be the key areas for disease prevention and control. Design: The research team performed a retrospective, spaciotemporal-clustering analysis of data about newly reported gonorrhea cases from January 2016 to December 2020 in Zhejiang province, using the China Information System for Disease Control and Prevention. Setting: The study took place at the Zhejiang Provincial Institute of Dermatology in Huzhou, China. Outcome Measures: The research team: (1) used the Geographic Information System software-ArcGIS 10.8 software to draw statistical maps; (2) conducted a spatial-pattern clustering analysis at the district or county level; (3) performed an autocorrelation analysis using Getis-Ord (Gi*) statistics to detect spatial patterns and the hotspots of gonorrhea incidence; and (4) used SaTScan9.7 to analyze the space-time clusters. Results: Zhejiang province reported 85 904 gonorrhea cases from 2016 to 2020, with a male to female ratio of 3.81:1. The average annual incidence rate of gonorrhea was 30.50 per 100 000 individuals in the population, ranging from 22.73 cases to 39.65 cases, and the annual incidence showed a significant downward trend over the five years (χ2 = 16.142, P < .001). The northern and central areas had a higher incidence than the southern area did. Autocorrelation analysis showed that the gonorrhea incidence had a significantly clustered distribution (Moran's I from 0.197 to 0.295, Z score from 4.749 to 6.909, P < .001). The high-high cluster areas were mainly in the urban districts of Hangzhou and some counties and districts of Jiaxing. The Gi* statistics further indicated that the hotspots of gonorrhea were mainly in Hangzhou, Jiaxing, and Huzhou. The Kuldorff's scan identified two clusters, mainly composed of 36 counties or districts in northern Zhejiang, such as Hangzhou and Jiaxing, and central Zhejiang, such as Jinhua and Shaoxing. Conclusions: The gonorrhea incidence rates in northern and central Zhejiang from 2016 to 2020 were higher than those in southern Zhejiang. An area of relatively higher risk for gonorrhea existed mainly in the urban districts of Hangzhou and some counties and districts of Jiaxing, Jinhua, and Shaoxing. In the future, the research team plans to focus on strengthening the prevention and control measures against gonorrhea in those areas.