Skeletal muscle index together with body mass index is associated with secondary osteoporosis in patients with rheumatoid arthritis.

OBJECTIVE: The objective of this study was to explore the associations of body mass index (BMI), fat mass index (FMI), skeletal mass index (SMI) and secondary osteoporosis (OP) in patients with rheumatoid arthritis (RA). METHODS: The bone mineral density (BMD) at sites of the femur neck (Neck), total hip (Hip) and lumbar vertebrae 1-4 (L1-4) was measured by dual-energy X-ray absorptiometry. The skeletal muscle index, body fat percentage and mineral content were measured by biological electrical impedance for calculating BMI, FMI and SMI. RESULTS: A total of 433 patient with RA and 158 healthy controls were enrolled. The BMDs at each site of the RA patients were lower compared with those of the healthy controls (p < 0.0001), and the prevalence of OP (36.1%, 160/443) and sarcopenia (65.2%, 288/443) in the RA patients were higher than those in the controls (12.7%, 20/158, p < 0.0001; 9.0%, 14/156, p < 0.0001). Significant differences in the BMD, FMI, SMI, mineral content, body fat percentage and skeletal muscle mass were found among the RA patients in the different BMI groups (p < 0.05). In RA patients with BMI < 18.5 kg/m2, the prevalence of OP in the RA patients with sarcopenia was similar to that in those without sarcopenia (44.4% vs. 66. 7%, χ2 = 0. 574, p = 0.449). In the RA patients with a normal BMI or who were overweight or obese, prevalence of OP in the RA patients with sarcopenia was significantly higher than that in the RA patients without sarcopenia (42.8% vs. 21.7%, χ2 = 10.951, p = 0.001; 61.1% vs. 13.0%, χ2 = 26.270, p < 0.0001). In the RA patients without sarcopenia, the prevalence of OP in the RA patients in the different BMI groups was different (p = 0.039). In the RA patients with sarcopenia, there was no significant difference in the prevalence of OP among the RA patients in the different BMI groups (p = 0. 128). The linear correlation analysis showed that the SMI in RA patients was positively correlated with the BMD of each site measured and BMI and FMI (p < 0.0001). However, there was a negative linear correlation between SMI and disease duration (p = 0.048). The logistic regression analysis found that SMI (OR = 0.569, p = 0.002, 95% CI 0.399-0.810), BMI (OR = 0.884, p = 0.01, 95% CI 0.805-0.971) and gender (1 = female, 2 = male) (OR = 0.097, p < 0.0001, 95% CI 0.040-0.236) were protective factors for OP in RA, while age (OR = 1.098, p < 0.0001, 95% CI 1.071-1.125) was the risk factor. CONCLUSION: BMI and SMI are associated with the occurrence of OP in RA patients, and both SMI and BMI are important protective factors for OP secondary to RA.

Epidemiological characteristics of patients with severe fever with thrombocytopenia syndrome in Dongyang City / 预防医学

Objective @#To investigate the epidemiological characteristics of severe fever with thrombocytopenia syndrome (SFTS) in Dongyang City, Zhejiang Province from 2017 to 2022, so as to provide insights into SFTS prevention and control. @*Methods@#Data pertaining to patients with SFTS in Dongyang City from 2017 to 2022 were collected from Notifiable Infectious Disease Reporting System of Chinese Disease Prevention and Control Information System. The epidemiological and clinical characteristics of patients with SFTS were descriptively analyzed, and the trends in incidence of SFTS was evaluated using annual percent change (APC). @*Results@#A total of 32 SFTS cases were reported in Dongyang City from 2017 to 2022, with mean annual incidence of 0.63/105, and 8 cases died, with a fatality rate of 25.00%. The incidence of SFTS appeared a tendency towards a rise from 2017 to 2022 (APC=40.697%, P<0.05). The male to female ratio of SFTS cases was 0.78∶1, and farmer was the predominant occupation (31 cases, 96.88%). SFTS predominantly occurred among individuals at ages of 51 to 69 years (20 cases, 62.50%), and the incidence peaked during the period between March and May and between July and August (28 cases, 87.50%). SFTS cases were reported in 11 out of the 18 townships (streets) in Dongyang City, with the highest number found in Zuocun Township (8 cases, 28.13%), and had the lowest platelet count of (41.46±5.19)×109 platelets/L, with the lowest count of (3.00 to 67.00) ×109 platelets/L. All the SFTS cases had a history of mountain forest and farmland activities 2 weeks prior to onset of the disease, and 5 cases (15.63%) had a history of tick bites.@*Conclusions@#The incidence of SFTS appeared a tendency towards a rise in Dongyang City from 2017 to 2022, and SFTS was highly prevalent in spring and summer, with high incidence among farmers. Intensified health education of SFTS is recommended among residents in high-incidence areas.

Mir-142-3P regulates MAPK protein family by inhibiting 14-3-3η to enhance bone marrow mesenchymal stem cells osteogenesis.

Clinical studies have found 14-3-3η to be associated with osteoporosis through undefined mechanisms. We aimed to investigate the role of 14-3-3η in osteoporosis and its potential associations with miRNAs. The Gene Expression Omnibus(GEO) and Human Protein Atlas 1 databases were analyzed to examine both the mRNA and protein expression of 14-3-3η in OP. Gene enrichment analyses were performed to explore the underlying mechanism of 14-3-3η based on DAVID. miRWalk was used to predict the associated miRNAs. The statistics were analysed by R software and SPSS software. 14-3-3η was overexpressed and knock down expressed in BMSCs by lentiviral vector transfecting. And BMSCs were induced by hypoxia. qRT-PCR and Western-Blot verified the expression of mRNA and protein. Scratch assay detected the migration of osteocytes. Co-immunoprecipitation and luciferase assay studied the 14-3-3η targeted protein and miRNA. overexpression and knock down of miRNA to verify the relationship of 14-3-3η and target genes. The 14-3-3η mRNA expression level was low in patients with osteoporosis, as corroborated by immunohistochemical staining images. Functional analyses revealed enrichment of the MAPK-associated cascade. 14-3-3η was correlated with MAPK family proteins and five key miRNAs, including mir-142-3p. In addition, 14-3-3η knockdown in BMSCs increased the mRNA and protein expression levels of Hif-α, VEGF, BMP-2, OPN, OST, and Runx2, and enhanced the cells migration ability. Under hypoxic conditions, Hif-α and BMP-2 protein expression levels were upregulated, whereas those of 14-3-3η and MAPK3 were downregulated. Co-immunoprecipitation experiments showed decreased binding of 14-3-3η to MAPK3. 14-3-3η knockdown produced the same results as hypoxia induction. Adding caspase3 inhibitor and knocking down 14-3-3η again prevented MAPK3 cleavage by caspase3 and inhibited BMP-2 expression. Moreover, under hypoxic conditions, miR-142-3P expression was upregulated and luciferase assays revealed 14-3-3η as its target gene. miR-142-3P overexpression decreased mRNA and protein levels of 14-3-3η and MAPK3, while increasing BMP-2 expression. miR-142-3P knockdown reversed these results. BMSC osteogenesis was suppressed by 14-3-3η, whereas miRNA-142-3p promoted it through the inhibition of 14-3-3η.

PepDRED: De Novo Peptide Design with Strong Binding Affinity for Target Protein.

De novo design of peptides that bind specifically to functional proteins is beneficial for diagnostics and therapeutics. However, complex permutations and combinations of amino acids pose significant challenges to the rational design of peptides with desirable stability and affinity. Herein, we develop a computational-based evolution method, namely, peptidomimetics-driven recognition elements design (PepDRED), to derive hemoglobin-inspired peptidomimetics. PepDRED mimics the natural evolutionism pipeline to generate stable apovariant (AVs) structures for wild-type counterparts via automated point mutations and validates their efficiency through free binding energy analysis and per residue energy decomposition analysis. For application demonstration, we applied PepDRED to design de novo peptides to bind FhuA, a typical TonB-dependent transporter (TBDT). TBDTs are Gram-negative bacterial outer membrane proteins responsible for iron transport and vital for bacterial resistance. PepDRED generated a pool of AVs and proceeded to reach an optimized peptide, AV440, with a remarkable binding affinity of -21 kcal/mol. AV440 is ∼2.5-fold stronger than the existing FhuA inhibitor Microcin J25. Network energy analysis further unveils that incorporating methionine (M42) in the N-terminal region significantly enhances inter-residue contacts and binding affinity. PepDRED offers a prompt and efficient in silico approach to develop potent peptide candidates for target proteins.

Corrigendum: Diseases of the musculoskeletal system and connective tissue and risk of breast cancer: mendelian randomization study in European and East Asian populations.

[This corrects the article DOI: 10.3389/fonc.2023.1170119.].

Two birds with one stone: Ratiometric sensing platform overcoming cross-interference for multiple-scenario detection and accurate discrimination of tetracycline analogs.

Environmental pollution caused by tetracycline antibiotics (TCs) is a major concern for public health worldwide. Trace detection and reliable discrimination of tetracycline and its analogs are consequently essential to determine the distribution characteristics of various tetracycline family members. Here, a dual-response sensor was constructed by integrating the fluorescence emission of fluorescein isothiocyanate (FITC) doped SiO2 and Eu3+. A portable Lab-on-Paper device is further fabricated through probe immobilization, which allows convenient visual detection of tetracycline using a smartphone. In addition, for the coexistence of multiple tetracycline analogs, dimensionality reduction via principal component analysis is applied to the spectra, realizing accurate differentiation of the four most widely used tetracycline analogs (tetracycline (TC), chlortetracycline (CTC), oxytetracycline (OTC), and doxycycline (DOX)). The dual-response nanoplatform enabled a wide-gamut color variation crossing from green to red, with limit of detection (LOD) of 2.9 nM and 89.8 nM for spectrometer- and paper-based sensors, respectively. Analytical performance was examined in multiple real samples, including food, environmental, and biological settings, confirming robust environmental adaptability and resistance. Compared to previous TC sensors, this method has several notable improvements, including improved ecological safety, accessibility, reproducibility, practicality, and anti-cross-interference capacity. These results highlight the potential of the proposed "two birds with one stone" strategy, providing an integrated methodology for synchronous quantitative detection and derivative identification toward environmental contaminants.

Diseases of the musculoskeletal system and connective tissue and risk of breast cancer: Mendelian randomization study in European and East Asian populations.

Objective: Associations between diseases of the musculoskeletal system and connective tissue (MSCTD) and breast cancer (BC) have not been elucidated completely. The purpose of this study was to investigate the associations of MSCTD, rheumatoid arthritis (RA), Sjogren syndrome (SS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermatomyositis (DM), polymyositis (PM), osteoarthritis (OA) of hip or knee, and ankylosing spondylitis (AS) with BC in European populations and East Asian populations using Mendelian randomized (MR) analysis. Methods: The genetic instruments linked to MSCTD, RA, SS, SLE, SSc, DM, PM, OA, and AS were chosen from the EBI database of complete genome-wide association studies (GWAS) summary data and the FinnGen consortium. The associations of genetic variants with BC were extracted from the Breast Cancer Association Consortium (BCAC). Two Sample MR was performed using summary data from GWAS, principally using the inverse variant weighted (IVW) method. Heterogeneity, pleiotropy, and sensitivity analyses were performed to evaluate the robustness of the results by weighted median, MR Egger, simple mode, weighted mode, and leave-one-out analysis. Results: In the European population, causal relationships between RA and BC (OR=1.04, 95%CI: 1.01-1.07, P=0.023), AS and BC (OR=1.21, 95%CI: 1.06-1.36, P=0.013) were confirmed. IVW analysis showed DM (OR=0.98, 95%CI: 0.96-0.99, P=0.026) and PM (OR=0.98, 95%CI: 0.97-0.99, P=0.002) were associated with slightly decreased risks of estrogen receptor (ER)+ BC, and MSCTD was associated with an increased risk of ER- BC (OR=1.85, 95%CI: 1.27-2.44, P=0.039). There was no causal relationship between SLE, SS, SSc, OA, and BC, neither ER+ BC nor ER- BC. However, in the East Asian population, IVW analysis showed that RA (OR=0.94, 95%CI: 0.89-0.99, P=0.0096) and SLE (OR=0.95, 95%CI: 0.92-0.99, P=0.0058) was associated with decreased risks of BC. Conclusions: This study suggests that causal relationships between patients with MSCTD and BC in the European population are different from those in the East Asian population, patients with RA and AS in the European population have an increased risk of BC, patients with MSCTD have increased risk of ER- BC in the European population, while patients with RA and SLE in the East Asian population have decreased risk of BC.

Sarcopenia May Be a Risk Factor for Osteoporosis in Chinese Patients with Rheumatoid Arthritis.

PURPOSE: Osteoporosis (OP) has been classically considered a co-morbidity of rheumatoid arthritis (RA). This investigation determined the clinical significance of sarcopenia in patients with RA combined with OP or whether sarcopenia influences RA when combined with OP. MATERIALS AND METHODS: Data pertaining to the duration of RA, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR) were collected from 549 RA cases and 158 healthy individuals. Disease activity score at 28 joints (DAS28), the body mass index (BMI), health assessment questionnaire (HAQ), bone mineral density (BMD), and Sharp score were compared between the 2 groups. RESULTS: The prevalence of OP (33.3% vs 12.7%, χ 2= 69.992, P < 0.0001) and sarcopenia (61.7% vs 9.0%, χ 2= 135.336, P < 0.01) was greater in patients with RA than in healthy controls. RA patients with sarcopenia had a higher incidence of OP at all measured sites than RA patients without sarcopenia (all P < 0.0001), and the incidence of OP was significantly higher than in patients with mild-to-moderate or severe RA without sarcopenia (P < 0.0001). Differences in age, gender, course of disease, CRP level, ESR, DAS28, BMI, HAQ, BMD, and Sharp score were statistically different between the RA with or without sarcopenia groups (P < 0.01). The incidence of OP and sarcopenia was higher in RA patients treated than not treated with glucocorticoids [GCs] (36.4% vs 29.3%, P < 0.05 and 66.1% vs 56.0%, respectively; P < 0.05). Logistic regression showed that the risk factors for OP in RA individuals were female (OR, 14.671; 95% CI, 6.877-31.300; P < 0.0001), age (OR, 1.100; 95% CI, 1.076-1.124; P < 0.0001), and sarcopenia (OR, 3.561; 95% CI, 2.214-5.726; P < 0.0001). CONCLUSION: OP and sarcopenia are common in RA patients. Sarcopenia may be a risk factor for OP occurrence in Chinese patients with RA.

Esophageal stenosis as an independent factor of poor prognosis in patients with ESCC treated with definitive chemoradiotherapy.

Aim: To evaluate the clinical outcome and elucidate the prognostic factors in patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (CRT). Patients: Data for patients newly diagnosed with ESCC receiving definitive CRT at our institution between 2012 and 2018 were retrospectively reviewed. Results: A total of 201 patients were included. Severe stenosis after radiotherapy was an independent factor relevant to prognosis. Maximal esophageal wall thickness, short-term responses, severe stenosis at diagnosis and a high neutrophil-to-lymphocyte ratio were independent risk factors for the occurrence of severe stenosis after radiotherapy. Conclusion: Severe stenosis after radiotherapy is a useful predictive indicator in patients with ESCC receiving definitive CRT. Further studies are needed to verify these findings.

This study aimed to identify valuable factors as predictive diagnostic markers for patients diagnosed with esophageal squamous cell carcinoma receiving chemoradiotherapy. In this retrospective study with patients, we have found that severe stenosis after radiotherapy has an independent predictive value for survival. Survival was also associated with maximal esophageal wall thickness, short-term responses, severe stenosis at diagnosis and a high neutrophil-to-lymphocyte ratio. Stenosis could be used as a parameter to predict survival in esophageal squamous cell carcinoma patients after chemoradiotherapy.

The Potential Regulatory Mechanism of lncRNA 122K13.12 and lncRNA 326C3.7 in Ankylosing Spondylitis.

This work aims to analyze and construct a novel competing endogenous RNA (ceRNA) network in ankylosing spondylitis (AS) with bone bridge formation, lncRNA. Using RNA sequencing and bioinformatics, we analyzed expression profiles of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in whole blood cells from 5 AS patients and 3 healthy individuals. Next, we verified the expression levels of candidate lncRNAs in 97 samples using the ΔΔCt value of real-time quantitative polymerase chain reaction (qRT-PCR). We used multivariate logistic regression analysis to screen lncRNAs and clinical indicators for use in the prediction model. Both SPSS 24.0 and R software were used for data analysis and prediction model construction. The results showed that compared with the normal controls, 205 long noncoding RNAs (lncRNAs), 961 microRNAs (miRNAs), and 200 mRNAs (DEmRNAs) were differentially expressed in the AS patients. We identified lncRNA 122K13.12 and lncRNA 326C3.7 among 205 lncRNAs differentially expressed between AS patients and healthy humans. Then, we noted that 30 miRNAs and five mRNAs formed a ceRNA network together with these two lncRNAs. These ceRNA networks might regulate the tumor necrosis factor (TNF) signaling pathway in AS development. In addition, the expression level of lncRNA 122K13.12 and lncRNA 326C3.7 correlated with various structural damage indicators in AS. Specifically, the lncRNA 326C3.7 expression level was an independent risk factor in bone bridge formation [area under the ROC curve (AUC) = 0.739 (0.609-0.870) and p = 0.003], and the best Youden Index was 0.405 (sensitivity = 0.800 and specificity = 0.605). Moreover, we constructed a lncRNA-based nomogram that could effectively predict bone bridge formation [AUC = 0.870 (0.780-0.959) and p < 0.001, and the best Youden Index was 0.637 (sensitivity = 0.900 and specificity = 0.737)]. In conclusion, we uncovered a unique ceRNA signaling network in AS with bone bridge formation and identified novel biomarkers and prediction models with the potential for clinical applications.

A Nomogram for Predicting the Risk of Radiotherapy-Related Esophageal Fistula in Esophageal Cancer Patients.

BACKGROUND: To construct and validate a nomogram for predicting the risk of esophageal fistula in esophageal cancer patients receiving radiotherapy. METHODS: A retrospective nested case-control study was performed, in which a total of 81 esophageal fistula patients and 243 controls from 2014 to 2020 in the First Affiliated Hospital of Anhui Medical University were enrolled. Factors included in the nomogram were determined by univariate and multiple logistic regression analysis. The following methods including ROC curve, C-index, calibration curves, Brier score, and decision curve analysis (DCA) were adopted to evaluate this nomogram. RESULTS: Multivariate logistic regression analysis showed that T4 stage, level 4 stenosis, ulcerative esophageal cancer, prealbumin, and maximum diameters of GTV and NLR were the independent risk factors of esophageal fistula. Accordingly, a nomogram incorporating the aforementioned six parameters was constructed. The AUC was 0.848 (95% CI 0.901-0.895), indicating a high prediction accuracy of this nomogram. Further evaluation of this model showed that the C-index was 0.847, while the bias-corrected C-index after internal validation was 0.833. The Brier score was 0.127. The calibration curves presented good concordance, and the DCA revealed promising clinical application. CONCLUSIONS: The nomogram presents accurate and applicable prediction for the esophageal fistula risk in esophageal cancer patients receiving radiotherapy.

Associations between weekly air pollution exposure and congenital heart disease.

BACKGROUND: The topic of congenital heart diseases (CHDs) has attracted more and more attentions. Accumulating evidence suggests that exposure to air pollutants during pregnancy is associated with CHDs, yet the results are inconsistent and study about weekly exposure is few. Our study evaluated the association between weekly air pollution and CHDs in Hefei, China. MATERIALS AND METHODS: Daily CHDs admission data were obtained from eight hospitals in Hefei from October 2015 to September 2017. Meteorological data and air quality were collected from China Meteorological Data Network. Distributed lag nonlinear model (DLNM) considering both the lag effect of exposure factors and the nonlinear relationship of exposure-reaction was used to assess the effect of weekly air pollutants exposure on CHDs admission. RESULTS: During the study period, totally 47,046 cases of perinatal infants were recruited, and the incidence of CHDs was 9.71 per thousand. The findings showed PM2.5, PM10, SO2 and NO2 significantly increased the risk of CHDs. Each 10 µg/m3 increase in PM2.5 during gestational weeks 20-26 increased the risk of CHDs. The susceptibility windows of PM10 (weeks 0-2 and weeks 25-29 of pregnancy), SO2 (weeks 8-16 and weeks 29-38) and NO2 (week 40), while the strongest effects of these 4 pollutants on CHDs were observed in week 22 (RR = 1.034, 95% CI: 1.007-1.062), week 0 (RR = 1.081, 95% CI: 1.02-1.146), week 37 (RR = 1.528, 95% CI: 1.085-2.153) and week 40 (RR = 1.171, 95% CI: 1.006-1.364), respectively. CONCLUSIONS: Air pollutants (SO2, NO2, PM10, and PM2.5) exposure could increase the risk of CHDs, while the most crucial susceptibility windows for the exposure were mainly in the second and third trimesters. Boys seemed to be more sensitive to air pollution. Our study contributes to the knowledge of the association between maternal exposure to air pollution and CHDs, but the associations need to be verified by further studies.

Inflammatory anemia may be an indicator for predicting disease activity and structural damage in Chinese patients with rheumatoid arthritis.

OBJECTIVES: This study aimed to investigate the relationship of serum hemoglobin (HB) level with disease activity and structural damage in Chinese patients with rheumatoid arthritis (RA). METHODS: A total of 890 RA patients and 890 normal subjects were enrolled in the case-control study. A HB threshold of< 110 g/L (women) and < 120 g/L (men) was used to determine anemia. All the patients were divided into three groups: non-anemia group (HB ≥ 120 g/L (male) or 110 g/L (female)), mild anemia group ((90 g/L < HB < lower limit of normal), and medium to severe anemia group (HB ≤ 90 g/L). Serum HB level and anemia prevalence between RA patients and normal subjects were compared. Associations of HB level with disease activity, structural damage, and function of joint in different groups were also investigated. RESULTS: The average of HB level in RA was (109.08 ± 17.96)g/l, which was lower than that in controls (136.75 ± 14.57)g/l (P < 0.001). Anemia was observed in 47% of the RA patients, while prevalence of anemia in control group was only 4.4%. In RA group, percentages of non-anemia, mild anemia, and medium to severe anemia were 47%, 38%, and 15%. Compared with non-anemia RA patients, RA patients with anemia had higher disease activity, severer structural damage and worse function of joint (P < 0.001). With the increase of anemia, the disease activity, structural damage, and dysfunction of joints increased significantly (P < 0.05-0.001). Linear regression analysis showed that HB level was negatively correlated with disease activity parameters, degree of joint destruction, and function (P < 0.05-0.001). Logistic regression indicated that serum HB level was protective factors for disease activity and structural damage in RA (P < 0.001). CONCLUSION: HB level was significantly related to disease activity and structural damage in RA patients.Key Points• Inflammatory anemia was popular (about a half) in patients with RA.• HB level was related to disease activity and structural damage in RA patients.