Proteomic and Metabolomic Characterization of COVID-19 Patient Sera.

Early detection and effective treatment of severe COVID-19 patients remain major challenges. Here, we performed proteomic and metabolomic profiling of sera from 46 COVID-19 and 53 control individuals. We then trained a machine learning model using proteomic and metabolomic measurements from a training cohort of 18 non-severe and 13 severe patients. The model was validated using 10 independent patients, 7 of which were correctly classified. Targeted proteomics and metabolomics assays were employed to further validate this molecular classifier in a second test cohort of 19 COVID-19 patients, leading to 16 correct assignments. We identified molecular changes in the sera of COVID-19 patients compared to other groups implicating dysregulation of macrophage, platelet degranulation, complement system pathways, and massive metabolic suppression. This study revealed characteristic protein and metabolite changes in the sera of severe COVID-19 patients, which might be used in selection of potential blood biomarkers for severity evaluation.

Proteomics Investigation of Diverse Serological Patterns in COVID-19.

Serum antibodies IgM and IgG are elevated during Coronavirus Disease 2019 (COVID-19) to defend against viral attacks. Atypical results such as negative and abnormally high antibody expression were frequently observed whereas the underlying molecular mechanisms are elusive. In our cohort of 144 COVID-19 patients, 3.5% were both IgM and IgG negative, whereas 29.2% remained only IgM negative. The remaining patients exhibited positive IgM and IgG expression, with 9.3% of them exhibiting over 20-fold higher titers of IgM than the others at their plateau. IgG titers in all of them were significantly boosted after vaccination in the second year. To investigate the underlying molecular mechanisms, we classed the patients into four groups with diverse serological patterns and analyzed their 2-year clinical indicators. Additionally, we collected 111 serum samples for TMTpro-based longitudinal proteomic profiling and characterized 1494 proteins in total. We found that the continuously negative IgM and IgG expression during COVID-19 were associated with mild inflammatory reactions and high T cell responses. Low levels of serum IgD, inferior complement 1 activation of complement cascades, and insufficient cellular immune responses might collectively lead to compensatory serological responses, causing overexpression of IgM. Serum CD163 was positively correlated with antibody titers during seroconversion. This study suggests that patients with negative serology still developed cellular immunity for viral defense and that high titers of IgM might not be favorable to COVID-19 recovery.

Large-scale array for radio astronomy on the farside (LARAF).

At the Royal Society meeting in 2023, we have mainly presented our lunar orbit array concept called DSL, and also briefly introduced a concept of a lunar surface array, LARAF. As the DSL concept had been presented before, in this article, we introduce the LARAF. We propose to build an array in the far side of the Moon, with a master station which handles the data collection and processing, and 20 stations with maximum baseline of 10 km. Each station consists of 12 membrane antenna units, and the stations are connected to the master station by power line and optical fibre. The array will make interferometric observation in the 0.1-50 MHz band during the lunar night, powered by regenerated fuel cells. The whole array can be carried to the lunar surface with a heavy rocket mission, and deployed with a rover in eight months. Such an array would be an important step in the long-term development of lunar-based ultralong wavelength radio astronomy. It has a sufficiently high sensitivity to observe many radio sources in the sky, though still short of the dark age fluctuations. We discuss the possible options in the power supply, data communication, deployment etc. This article is part of a discussion meeting issue 'Astronomy from the Moon: the next decades (part 2)'.

Potential Use of Serum Proteomics for Monitoring COVID-19 Progression to Complement RT-PCR Detection.

RT-PCR is the primary method to diagnose COVID-19 and is also used to monitor the disease course. This approach, however, suffers from false negatives due to RNA instability and poses a high risk to medical practitioners. Here, we investigated the potential of using serum proteomics to predict viral nucleic acid positivity during COVID-19. We analyzed the proteome of 275 inactivated serum samples from 54 out of 144 COVID-19 patients and shortlisted 42 regulated proteins in the severe group and 12 in the non-severe group. Using these regulated proteins and several key clinical indexes, including days after symptoms onset, platelet counts, and magnesium, we developed two machine learning models to predict nucleic acid positivity, with an AUC of 0.94 in severe cases and 0.89 in non-severe cases, respectively. Our data suggest the potential of using a serum protein-based machine learning model to monitor COVID-19 progression, thus complementing swab RT-PCR tests. More efforts are required to promote this approach into clinical practice since mass spectrometry-based protein measurement is not currently widely accessible in clinic.

Estimation of average treatment effect based on a multi-index propensity score.

BACKGROUND: Estimating the average effect of a treatment, exposure, or intervention on health outcomes is a primary aim of many medical studies. However, unbalanced covariates between groups can lead to confounding bias when using observational data to estimate the average treatment effect (ATE). In this study, we proposed an estimator to correct confounding bias and provide multiple protection for estimation consistency. METHODS: With reference to the kernel function-based double-index propensity score (Ker.DiPS) estimator, we proposed the artificial neural network-based multi-index propensity score (ANN.MiPS) estimator. The ANN.MiPS estimator employed the artificial neural network to estimate the MiPS that combines the information from multiple candidate models for propensity score and outcome regression. A Monte Carlo simulation study was designed to evaluate the performance of the proposed ANN.MiPS estimator. Furthermore, we applied our estimator to real data to discuss its practicability. RESULTS: The simulation study showed the bias of the ANN.MiPS estimators is very small and the standard error is similar if any one of the candidate models is correctly specified under all evaluated sample sizes, treatment rates, and covariate types. Compared to the kernel function-based estimator, the ANN.MiPS estimator usually yields smaller standard error when the correct model is incorporated in the estimator. The empirical study indicated the point estimation for ATE and its bootstrap standard error of the ANN.MiPS estimator is stable under different model specifications. CONCLUSIONS: The proposed estimator extended the combination of information from two models to multiple models and achieved multiply robust estimation for ATE. Extra efficiency was gained by our estimator compared to the kernel-based estimator. The proposed estimator provided a novel approach for estimating the causal effects in observational studies.

Aspirin inhibits the growth of hypertrophic scar in rabbit ears via regulating Wnt/ß-catenin signal pathway. / 阿司匹林通过调控Wnt/ß-cateninä¿¡å·é€šè·¯æŠ‘åˆ¶å ”è€³å¢žç”Ÿæ€§ç˜¢ç—•çš„ç”Ÿé•¿.

OBJECTIVES: Steroidal anti-inflammatory drugs have certain side effects in the treatment of hypertrophic scar, and the scar recurrence is easy after withdrawal of steroid anti-inflammatory drugs. Finding reliable alternative drugs is an effective means to improve this defect. Aspirin, a traditional non-steroidal anti-inflammatory drug, is safe for topical use and has anti-inflammatory effects similar to those of steroidal anti-inflammatory drugs, which may have similar effects on the treatment of hypertrophic scar. This study aims to investigate the inhibitory effect of aspirin on the proliferation of hypertrophic scar in rabbit ears and the underlying mechanism. METHODS: The rabbit ear hypertrophic scar models were prepared. The rabbits were randomly divided into a normal skin group (group A), a blank control group (group B), a 0.9% NaCl group (group C), a 0.2% aspirin group (group D), a 0.5% aspirin group (group E), a 2% aspirin group (group F), and a triamcinolone acetonide group (group G). Macroscopic observation of hyperplasia was performed 8 weeks after local injection of the scar, followed by collecting the scar tissue samples for HE staining, Masson staining, and immunohistochemistry, respectively to assess the proliferation of fibroblasts and collagen fibers, and calculate the hypertrophic index, microvessel density, and immunohistochemical score. RESULTS: All rabbit ear hypertrophic scar models were successfully constructed. In groups B and C, the hypertrophic scar edge was irregular, with reddish protruding epidermis, significant contracture and hard touch. In group D, E, and F, with the increase of aspirin administration concentration, the scar became thinner and gradually flat, the proliferation of fibrocytes and collagen fibers was weakened, and the hypertrophic index was gradually decreased (P<0.05). Immunohistochemistry showed that the expression of ß-catenin was decreased in the group D, E and F in turn, and the immunohistochemical score was gradually decreased (P<0.05). There was no significant difference in hypertrophic index, microvessel density, and immunohistochemical score (all P>0.05). CONCLUSIONS: Local injection of aspirin can reduce the generation of hypertrophic scar in a dose-dependent manner within a certain concentration range; aspirin inhibits the growth of hypertrophic scar in rabbit ears by inhibiting Wnt/ß-catenin signal pathway; 2% aspirin and 40 mg/mL triamcinolone acetonide have similar curative efficacy on hypertrophic scar.

Proteomic and metabolomic investigation of serum lactate dehydrogenase elevation in COVID-19 patients.

Serum lactate dehydrogenase (LDH) has been established as a prognostic indicator given its differential expression in COVID-19 patients. However, the molecular mechanisms underneath remain poorly understood. In this study, 144 COVID-19 patients were enrolled to monitor the clinical and laboratory parameters over 3 weeks. Serum LDH was shown elevated in the COVID-19 patients on admission and declined throughout disease course, and its ability to classify patient severity outperformed other biochemical indicators. A threshold of 247 U/L serum LDH on admission was determined for severity prognosis. Next, we classified a subset of 14 patients into high- and low-risk groups based on serum LDH expression and compared their quantitative serum proteomic and metabolomic differences. The results showed that COVID-19 patients with high serum LDH exhibited differentially expressed blood coagulation and immune responses including acute inflammatory responses, platelet degranulation, complement cascade, as well as multiple different metabolic responses including lipid metabolism, protein ubiquitination and pyruvate fermentation. Specifically, activation of hypoxia responses was highlighted in patients with high LDH expressions. Taken together, our data showed that serum LDH levels are associated with COVID-19 severity, and that elevated serum LDH might be consequences of hypoxia and tissue injuries induced by inflammation.

Incidence of and risk factors associated with lung metastases in newly diagnosed epithelial ovarian cancer with a look on prognosis after diagnosis: a population-based cohort study of the SEER database.

PURPOSE: Patients with lung metastases (LM) from epithelial ovarian cancer (EOC) (EOCLM) usually have a poor prognosis. However, there is no consensus on the optimal management of these patients. In this study, we aimed to take a look at the incidence of LM and factors associated with its occurrence as well as the prognosis in newly diagnosed EOC with LM on a population level. METHODS: EOC patients diagnosed between the years 2010 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) program database. Multivariable logistic regression and multivariable Cox regression were used to investigate the factors that could predict the occurrence of and prognosis after diagnosis of EOC with LM. RESULTS: Of the 33,418 qualified EOC patients, 2240 (6.7%) were noted to have LMs at the time of EOC diagnosis. Higher T stage, N1 stage, advanced tumor grade, and elevated cancer antigen-125 levels were found to be associated with a higher risk of having LM at the time of EOC diagnosis. The median survival time after diagnosis with EOCLM was found to be 13.0 months (interquartile range: 3.0-34.0 months). Being unmarried and having mucinous histology were both associated with increased all-cause death risk from EOCLM. However, the primary tumor originated from the midline of ovaries, surgical management, and whether patient received chemotherapy or not predicted improved overall survival. The median survival time of patients was significantly longer for EOCLM cases managed surgically (31.0 months) versus those who did not have surgery (4.0 months), as well as EOCLM cases received chemotherapy (23.0 months) versus those who did not have chemotherapy (2.0 months). CONCLUSION: This retrospective cohort study showed that de novo LM was infrequent in EOC patients overall and when present predicted poor prognosis. The findings can be potentially useful in formulating for follow-up strategies, screening tools, and personalized interventions.

Ameliorating Effects of Transcutaneous Electrical Acustimulation Combined With Deep Breathing Training on Refractory Gastroesophageal Reflux Disease Mediated via the Autonomic Pathway.

AIMS: To investigate the effects and possible mechanisms of transcutaneous electrical acustimulation (TEA) combined with deep breathing training (DBT) on refractory gastroesophageal reflux disease (rGERD). METHODS: Twenty-one patients with rGERD were recruited and randomly assigned to receive either only esomeprazole (ESO, 20 mg bid) (group A, n = 7), TEA + DBT + ESO (group B, n = 7), or sham-TEA + DBT + ESO (group C, n = 7) in a four-week study. The reflux diagnostic questionnaire (RDQ) score and heart rate variability (HRV) were recorded and evaluated at baseline and at the end of each treatment. Blood samples were collected for the measurement of serum acetylcholine (Ach) and nitric oxide (NO). Esophageal manometry and 24-hour pH monitoring were performed before and after the treatment. RESULTS: After treatment, 1) the participants in group B had significantly lower scores of RDQ and DeMeester and increased lower esophageal sphincter pressure (LESP) than those in group C (all p < 0.05), suggesting the role of TEA; 2) low frequency band (LF)/(LF + HF) ratio in groups B and C was decreased, compared with group A (p = 0.010, p = 0.042, respectively); high frequency band (HF)/(LF + HF) ratio in B and C groups was significantly increased, compared with group A (p = 0.010, p = 0.042, respectively); 3) The serum Ach in groups B and C was significantly higher than group A (p = 0.022, p = 0.046, respectively); the serum NO in groups B and C was significantly lower than group A (p = 0.010, p = 0.027, respectively). CONCLUSIONS: TEA combined with the DBT can effectively improve the reflux symptoms in rGERD patients by increasing LESP and reducing gastroesophageal reflux, which may be mediated via the autonomic and enteric mechanisms.

Viability and Biomechanics of Bare Diced Cartilage Grafts in Experimental Study.

OBJECTIVE: To assess the viability and biomechanics of bare diced cartilage grafts. METHODS: Cartilage samples were collected from 1 ear in 15 rabbits as well as costal cartilage. Each rabbit was inserted bare diced- and single-strip costal-cartilage grafts, respectively, into paraspinal subcutaneous pockets: after euthanasia at 2 months, specimens were weighed, with diced cartilage grafts examined histomorphologically by hematoxylin-eosin staining, masson trichrome staining, and immunohistochemistry. Finally, biomechanical properties of grafts were assessed. RESULTS: Bare diced cartilage grafts were connected into an integrated mass after 2 months, and inward growth of fibrous tissues and angiogenesis were observed. Mean wet weights of diced cartilage grafts were 1.603 ±â€Š0.278 and 1.662 ±â€Š0.204 g pre- and postoperation, respectively; those of costal cartilage grafts were 0.053 ±â€Š0.008 and 0.058 ±â€Š0.008 g, respectively. In compression assays, mean modulus values of elasticity at yield in diced- and costal-cartilage grafts were 7.65 ±â€Š0.59 and 22.30 ±â€Š1.15 MPa, respectively (P < 0.05); mean stress values were 4.07 ±â€Š0.38 and 12.50 ±â€Š1.15 MPa, respectively (P < 0.05). In the tensile test, mean modulus values of elasticity at yield of diced- and costal-cartilage grafts were 4.70 ±â€Š0.78 and 10.59 ±â€Š1.39 MPa, respectively (P < 0.05), mean stress values were 0.82 ±â€Š0.05 and 1.76 ±â€Š0.21 MPa, respectively (P < 0.05). CONCLUSIONS: Diced cartilage grafts had favorable viability and growth. Despite reduced elasticity and stress values, they still can be served as substitute for supportive filling materials.

Unveiling Dynamic Changes and Regulatory Mechanisms of T Cell Subsets in Sepsis Pathogenesis.

Purpose: The pathogenesis of T cell subsets in sepsis during the body's resistance to infection is currently unknown. We aimed to investigate the dynamics and molecular mechanisms of T cells during the development of sepsis. Patients and Methods: Perform single-cell data analysis on peripheral blood mononuclear cells (PBMCs) specimen samples from seven healthy controls, five early-stage sepsis patients, and four late sepsis patients, and the atlas were mapped and analyzed using reference mapping to identify the T cell subpopulations specific to early sepsis. Expression network upstream to investigate the changes of regulatory transcription factors and pathways by pySCENIC. Results: Twenty-two CD4+ T-cell subpopulations and 10 CD8+ T-cell subpopulations were identified by mapping analysis. At the early stage of sepsis, we observed altered ratios of multiple immune cells in PBMCs. Three cell types CD4 Tn cells, CD8 (GZMK+ early Tem), and CD8 (ZNF683+CXCR6- Tm) showed an upward trend (p < 0.05) in the early stages of sepsis compared to normal and returned to normal levels after two weeks. In addition, we found the presence of four sepsis-specific transcription factors (MXI1, CHD1, ARID5A, KLF9) in these three types of cells, which were validated in two external datasets. The differentially expressed genes in CD4 Tn cells, CD8 (GZMK+ early Tem), and CD8 (ZNF683+CXCR6- Tm) cells between the healthy group and the early-stage sepsis group are commonly enriched in the allograft rejection pathway. In addition, it was found that CD8 cells exhibit a trend towards differentiation into CD8 Temra cells in sepsis. Conclusion: We successfully depicted the dynamic changes of T cell subsets during sepsis onset and progression, which provides important clues for an in-depth understanding of T cells' function and regulatory mechanisms during sepsis pathogenesis.

Metagenomic next-generation sequencing testing from the perspective of clinical benefits.

BACKGROUND AND AIMS: Metagenomic next-generation sequencing (mNGS) provided promising supports to rapid pathogen diagnosis. However, summary of scientific application strategy based on clinical practice study is still necessary for enhancing clinical benefits. MATERIALS AND METHODS: We conducted a retrospective analysis of 775 samples from patients with suspected infectious diseases (IDs). Based on final diagnosis, diagnostic performance, clinical relevance and clinical impact of mNGS among various clinical settings were assessed, and influencing factors were deeply explored. RESULTS: 84.26 % tests were clinically relevant; sample, but not sequencing, was the influencing factor. 40.77 % tests contributed to positive clinical impact, while 0.13 % and 59.10 % to negative and no impact respectively. mNGS utility in patients with IDs, definite infection site, BALF and CSF contributed to higher positive impacts. Days of empirical treatment before sampling ≤ 5 in ICU and ≤ 2 or between 11 and 20 in non-ICU, and reporting in 2 days brought about higher clinical benefit rates. Characteristic pathogen spectrum between ICU and non-ICU cases were revealed. CONCLUSIONS: Our findings highlighted clinical benefits from mNGS varied among different clinical settings, and elucidated choices on patients, samples, sampling and reporting time were four key factors. Rational strategy should be concerned to promote scientific application of mNGS and better improve clinical value.

Age-Specific Association Between Visit-to-Visit Blood Pressure Variability and Hearing Loss: A Population-Based Cohort Study.

Background and Objectives: Hearing loss is common and undertreated, and the impact of blood pressure variability (BPV) on the development of hearing loss remains unclear. We aimed to examine the age-specific association between visit-to-visit BPV and hearing loss. Research Design and Methods: This nationally representative cohort study included 3,939 adults over 50 years from the Health and Retirement Study in the United States. Variabilities of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were assessed by standard deviation (SD), coefficient of variation, and variability independent of the mean (VIM), using SBP and DBP from 3 visits. Hearing loss was assessed by self-rated questions. Cox proportional risk models were used to evaluate age-specific associations (50-64, 65-79, and ≥80 years) between BPV and hearing loss. The generalized additive Cox models were further used to visualize the combined effect of age and BPV. Results: During the follow-up up to 7.0 years, 700 participants developed hearing loss. Among people aged under 65 years, we observed a 36% increased risk of hearing loss with per-SD increment in VIM of SBP (hazard ratio [HR] per SD 1.36, 95% confidence interval [CI] 1.13-1.63) and a slightly significant association between VIM of DBP (HR per SD 1.21, 95% CI 1.01-1.45) and hearing loss. We did not observe significant associations among groups aged over 65 years (p > .05). The generalized additive Cox models also showed younger participants had stronger associations between BPV and hearing loss. Discussion and Implications: Higher visit-to-visit variabilities of SBP were associated with an increased risk of hearing loss in middle-aged adults (50-65 years). Intervention in early BPV may help decrease hearing loss in adults aged over 50 years.

Establishment and evaluation of a nomogram for predicting the survival outcomes of patients with diffuse large B-cell lymphoma based on International Prognostic Index scores and clinical indicators.

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma, treatment outcomes of patients vary greatly. The current International Prognostic Index (IPI) is not enough to distinguish patients with poor prognosis, and genetic testing is very expensive, so a inexpensive risk prediction tool should be developed for clinicians to quickly identify the poor prognosis of DLBCL patients. Methods: DLBCL patients (n=420; 18-80 years old) who received a combination of cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) with or without rituximab (R-CHOP) at our hospital between 2008 and 2017 were included in the study. Potential predictors of survival were determined by univariate and multivariate Cox regression analyses, and significant variables were used to construct predictive nomograms. The new prediction models were assessed using concordance indexes (C-indexes), calibration curves, and their clinical utility was assessed by decision curve analyses (DCAs). Results: The 5-year overall survival (OS) rate was 70.62% and the 5-year progression-free survival (PFS) rate was 59.02%. The multivariate Cox analysis indicated that IPI, Ki-67, the lymphocyte/monocyte ratio, and first-line treatment with rituximab were significantly associated with survival. The C-index results indicated that a predictive model that included these variables had better discriminability for OS (0.73 vs. 0.67) and PFS (0.68 vs. 0.63) than the IPI-based model. The calibration plots showed good agreement with observations and nomogram predictions. The DCAs demonstrated the clinical value of the nomograms. Conclusions: Our study identified prognostic factors in patients who were newly diagnosed with DLBCL to construct an individualized risk prediction model, combined IPI with common clinical indicators. Our model might be a valuable tool that could be used to predict the prognosis of DLBCL patients who receive standard first-line treatment regimens. It enables clinicians to quickly identify some patients with possible poor prognosis and choose more active treatment for patients, such as chimeric antigen receptor T-cell (CART) Immunotherapy and other new drugs therapy, so as to prolong the PFS and OS of patients.

Association of depression with all-cause and cardiovascular mortality among US adults with high and low baseline risk of cardiovascular disease.

The intervention of depression was considered a prevention and treatment option for cardiovascular disease (CVD). However, evidence regarding whether association of depression with mortality differed among people at high or low risk of CVD yielded conflicting results. We aimed to investigate associations between depression and all-cause and CVD mortality among 3854 and 3044 US adults at high and low baseline risk of CVD, respectively. Among participants at high risk of CVD, depression and per 5-point increase in PHQ-9 score were associated with 81% (HR=1.81, 95%CI: 1.15-2.86) and 33% (HR=1.33, 95%CI: 1.14-1.55) increased all-cause mortality, respectively. We did not find statistically significant associations between depression (HR=1.40, 95%CI: 0.67-2.95) and PHQ-9 score (HR=1.28, 95%CI: 1.00-1.63) with CVD mortality due to a small number of mortality events. Among people with low risk of CVD, each 5-point increment in PHQ-9 score was associated with all-cause mortality (HR=1.26, 95%CI: 1.02-1.56), while there was no statistically significant association of depression with all-cause mortality (HR=1.69, 95%CI: 0.75-3.81) and CVD mortality (HR=1.99, 95%CI: 0.83-4.81). This study found that depression was associated with all-cause mortality among individuals at a high baseline risk of CVD, but no significant association was observed in people at a low baseline risk of CVD.

Pan-cancer and single-cell analysis reveal the prognostic value and immune response of NQO1.

Background: Overexpression of the NAD(P)H: Quinone Oxidoreductase 1 (NQOI) gene has been linked with tumor progression, aggressiveness, drug resistance, and poor patient prognosis. Most research has described the biological function of the NQO1 in certain types and limited samples, but a comprehensive understanding of the NQO1's function and clinical importance at the pan-cancer level is scarce. More research is needed to understand the role of NQO1 in tumor infiltration, and immune checkpoint inhibitors in various cancers are needed. Methods: The NQO1 expression data for 33 types of pan-cancer and their association with the prognosis, pathologic stage, gender, immune cell infiltration, the tumor mutation burden, microsatellite instability, immune checkpoints, enrichment pathways, and the half-maximal inhibitory concentration (IC50) were downloaded from public databases. Results: Our findings indicate that the NQO1 gene was significantly upregulated in most cancer types. The Cox regression analysis showed that overexpression of the NQO1 gene was related to poor OS in Glioma, uveal melanoma, head and neck squamous cell carcinoma, kidney renal papillary cell carcinoma, and adrenocortical carcinoma. NQO1 mRNA expression positively correlated with infiltrating immune cells and checkpoint molecule levels. The single-cell analysis revealed a potential relationship between the NQO1 mRNA expression levels and the infiltration of immune cells and stromal cells in bladder urothelial carcinoma, invasive breast carcinoma, and colorectal cancer. Conversely, a negative association was noted between various drugs (17-AAG, Lapatinib, Trametinib, PD-0325901) and the NQO1 mRNA expression levels. Conclusion: NQO1 expression was significantly associated with prognosis, immune infiltrates, and drug resistance in multiple cancer types. The inhibition of the NQO1-dependent signaling pathways may provide a promising strategy for developing new cancer-targeted therapies.

Association of dietary calcium with mortality from all causes, cardiovascular disease and cancer in people with hypertension.

Association between calcium intake and premature mortality in the general population has been well studied, but little is known about the association among specific populations. The authors aim to evaluate the association among people with hypertension and to provide a proper reference range of dietary calcium intake. This prospective cohort study included 8534 US adults with hypertension from National Health and Nutrition Examination Survey cycles 2003-2014. Dietary calcium intakes were self-reported and mortality status was ascertained by National Death Index records. During a median follow-up of 5.9 years, 1357 death occurred. Compared with participants of dietary calcium intake in quintile 1, participants in quintiles 2 and 4 had a 27% (HR: 0.73, 95% CI: 0.60-0.89) and a 29% lower risk (HR: 0.71, 95% CI: 0.57-0.88) of all-cause mortality respectively. The authors also observed a 34% lower risk (HR: 0.66, 95% CI: 0.45-0.97) of CVD death among participants in quintile 3 and a 37% lower risk (HR: 0.63, 95% CI: 0.40-0.99) of cancer-related death in participants in quintile 4 respectively. Restricted cubic spline (RCS) regression revealed a consistent protective effect of dietary calcium in participants with a daily intake of over 1000 mg, but a daily intake over 1200 mg fails to show further protective effect. Our findings suggest that elevated dietary calcium was associated with lower mortality risk from all-causes, cardiovascular disease (CVD) and cancer, and supplying sufficient dietary calcium intake, between 1000 and 1200 mg per day, in people with hypertension may be considered cost-effective to decrease risk of premature death.

Parameters and Morphological Changes of Erythrocytes and Platelets of COVID-19 Subjects: A Longitudinal Cohort Study.

Purpose: Information about dynamic changes occurring in the parameters and morphology of erythrocytes and platelets during the coronavirus disease 2019 (COVID-19) infection and convalescence is scarce. To explore potential associations between dynamic erythrocyte and platelet parameters, morphological changes, and the course or severity of the disease is essential. Patients and Methods: From January 17th, 2020, to February 20th, 2022, we followed up on 35 patients with non-severe and 11 patients with severe COVID-19 following their discharge. We collected clinical features, dynamic complete blood count (CBC), and peripheral blood smears (PBS) and analyzed parameter and morphological changes of erythrocytes and platelets depending on the course or severity of the disease. The course of the disease included four periods, namely onset (T1), discharge (T2), 1-year follow-up (T3), and 2-year follow-up (T4). Results: Red blood cell (RBC) counts and hemoglobin were the lowest in T2, followed by T1, and lower in T1 and T2 than in T3 and T4. Inversely, the red blood cell distribution width (RDW) was the highest in T2, followed by T1, and higher than in T3 and T4. Compared to non-severe patients, the platelet of severe patients was lower in T1 and T2. In contrast, the mean platelet volume (MPV) and platelet distribution width (PDW) tended to be higher in severe patients. Similarly, anisocytosis was more common in peripheral blood smears at early stages and in severe patients. Finally, large platelets were more common in severe patients. Conclusion: Anisocytosis of erythrocytes and large platelets are found in patients with severe COVID-19, these changes may help primary hospitals to identify patients with a high risk of severe COVID-19 at an early stage.

Intestinal Ultrasound Combined with Blood Inflammatory Markers Is a More Efficient Tool in Evaluating Severity of Crohn's Disease: A Pilot Study.

Background and Aims: Intestinal ultrasound (IUS) is considered a nonirradiating, noninvasive, well-tolerated, and valuable tool for objectively assessing Crohn's disease (CD) activity. However, there is no widely accepted intestinal ultrasound scoring system. This study is aimed at evaluating the efficacy of IUS key parameters, the International Bowel Ultrasound Activity Score (IBUS-SAS), and IBUS-SAS combined with blood inflammatory markers in assessing CD activity. Methods: 40 CD patients were reviewed in this retrospective study and were divided into the moderate-severe group (n = 25) and nonmoderate-severe group (n = 15) based on a simplified endoscopic score of Crohn's disease (SES-CD). Double-balloon enteroscopy/colonoscopy were reviewed by three gastroenterologists. A transabdominal ultrasound was performed by two ultrasound specialists. Blood inflammatory markers were measured from morning samples. Results: In evaluating moderate to severe CD patients, (1) IBUS-SAS had a good predictive effect with an area-under-the-curve (AUC) of 0.855 (P < 0.001); (2) IUS key parameters (including BWT, CDS, BWS, and I-fat) yielded good predictive effects with AUC of 0.811, 0.731, 0.724, and 0.747, respectively (P < 0.001); (3) blood inflammatory markers (including ESR, CRP, PLR, MLR, and NLR) also had good predictive effects with AUC of 0.771, 0.837, 0.728, 0.743, and 0.775, respectively (P < 0.001); (4) IBUS-SAS combined with ESR and CRP exerted the best predictive effect with the highest AUC of 0.912 (95% CI: 0.823-1.000), and the sensitivity and specificity were 88.0% and 80.0%, respectively (P < 0.001). Conclusion: IBUS-SAS combined with ESR and CRP is a more efficient tool than IBUS-SAS alone or inflammatory markers alone in evaluating CD patients with moderate to severe disease activity.

Associations between trajectories of social participation and functional ability among older adults: Results from the China Health and Retirement Longitudinal Study.

Introduction: Functional ability (FA) and social participation (SP) are important indicators of healthy aging, both their trajectories are heterogeneous. It is little known about how the SP trajectories affects FA trajectories. Methods: FA was assessed by 20 items covering the ability of meeting basic needs and mobility. SP was assessed by frequency of participating in 10 social activities. Group-based trajectory modeling (GBTM) was used to identify the trajectories of FA and SP of the participants. Results: Two FA trajectories were identified: low baseline-decline tendency (16.1%) and high baseline-stable tendency (83.9%) trajectories. Two SP trajectories were also identified: low baseline-stable tendency (58.5%) and high baseline-increase tendency (41.5%) trajectories. After controlling for the potential covariates, participants among the high baseline-increase tendency SP trajectory group also had significantly higher odds ratios to be belonged in high baseline-stable tendency FA trajectory group (ORs = 2.64, 95%CI = 1.98-3.05). Conclusions: High-increasing social participation had a protective effect to maintain high baseline-stable tendency functional ability among older adults. These findings suggest social participation appears to have great benefits on promoting healthy aging in China.