Improved small vessel visibility in diabetic foot arteriography using dual-energy CT.

AIM: To test the feasibility and performance of dual-energy computed tomography (DECT) in foot arteriography of diabetic patients, where contrast medium is largely reduced within the small vessels. MATERIALS AND METHODS: A total of 50 diabetic patients were enrolled prospectively, where DECT was acquired immediately after the CT angiography (CTA, group A) of the lower extremity. Two images were derived from the DECT data, one optimal virtual monochromatic image (VMI, group B) and one fusion image (group C), both of which were compared against the CTA image for visualising the foot arteries. The contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were evaluated. The arterial course and contrast were graded each using a five-point scale. The clarity of small vessel depiction was quantified by comparing the number of plantar metatarsal arteries found in the maximum intensity projection image. RESULTS: The median CNRs and SNRs obtained in group B were approximately 45% and 20% higher than those in groups A and C, respectively (p<0.05). Group B also received higher subjective scores on the posterior tibial artery and the foot arteries (all >3) than groups A and C. The number of visible branches of the plantar metatarsal arteries was found to be substantially higher (p<0.05) in group B (median=6) than in groups A (median=2) and C (median=4). CONCLUSION: DECT was found to be superior to conventional CTA in foot arteriography, and beyond the lower extremity, it might be a general favourable solution for imaging regions with small vessels and reduced contrast medium.

Long-term prognostic value of thyroid hormones in left ventricular noncompaction.

PURPOSE: Thyroid function is closely related to the prognosis of cardiovascular diseases. This study aimed to explore the predictive value of thyroid hormones for adverse cardiovascular outcomes in left ventricular noncompaction (LVNC). METHODS: This longitudinal cohort study enrolled 388 consecutive LVNC patients with complete thyroid function profiles and comprehensive cardiovascular assessment. Potential predictors for adverse outcomes were thoroughly evaluated. RESULTS: Over a median follow-up of 5.22 years, primary outcome (the combination of cardiovascular mortality and heart transplantation) occurred in 98 (25.3%) patients. For secondary outcomes, 75 (19.3%) patients died and 130 (33.5%) patients experienced major adverse cardiovascular events (MACE). Multivariable Cox analysis identified that free triiodothyronine (FT3) was independently associated with both primary (HR 0.455, 95%CI 0.313-0.664) and secondary (HR 0.547, 95%CI 0.349-0.858; HR 0.663, 95%CI 0.475-0.925) outcomes. Restricted cubic spline analysis illustrated that the risk for adverse outcomes increased significantly with the decline of serum FT3. The LVNC cohort was further stratified according to tertiles of FT3 levels. Individuals with lower FT3 levels in the tertile 1 group suffered from severe cardiac dysfunction and remodeling, resulting in higher incidence of mortality and MACE (Log-rank P < 0.001). Subgroup analysis revealed that lower concentration of FT3 was linked to worse prognosis, particularly for patients with left atrial diameter ≥ 40 mm or left ventricular ejection fraction ≤ 35%. Adding FT3 to the pre-existing risk score for MACE in LVNC improved its predictive performance. CONCLUSION: Through the long-term investigation on a large LVNC cohort, we demonstrated that low FT3 level was an independent predictor for adverse cardiovascular outcomes.

Barriers to school-based health programs implementation in basic schools in Ghana: education stakeholders' perspective.

School health has been identified as a neglected aspect of primary health care in Ghana, leading to compromised health, well-being and life satisfaction among students. To address this concern, this study identified the barriers hindering the implementation of school-based health programs in Ghana. It employed a qualitative approach, including 116 respondents who participated in interviews. The collected data were analyzed using thematic analysis with the aid of NVivo software. In line with the research objective, findings show that the implementation of school-based health programs faces several teething challenges that serve as barriers to the success and sustainability of the programs. These barriers included resource constraints; a lack of adequate parental and community participation and a lack of adequate collaboration between stakeholders' management and leadership issues, governance issues and political issues. The findings from the study have a relevant and innovative contribution to achieving good health and well-being and quality education as part of the 2030 Agenda for Sustainable Development Goals and shaping primary healthcare management in the context of a developing country. It recommends that policymakers and health practitioners pay special attention to school-based health programs as a key strategy for primary health care management in developing countries.

Prognostic significance of serum cystatin C in acute brainstem infarctions patients.

OBJECTIVES: Some studies show that high circulating cystatin C (CysC) may predict cardiovascular events and death after ischemic stroke onset. However, the association between serum CysC and outcome in ischemic stroke patients remains contradictory. We sought to assess the association between a specific stroke subgroup, brainstem infarction (BSI) and serum CysC. MATERIALS AND METHODS: A total of 324 acute BSI patients were included in the study. Serum CysC was used to calculate estimated glomerular filtration rate (eGFRCysC) at baseline. Modified Rankin scale score ((mRS) ≥3) six months after acute BSI indicates poor functional outcome. Patients were categorized into two groups according to mRS and eGFRCysC. Logistic regression analyses were performed to determine independent risk factors. RESULTS: Lower eGFRCysC was associated with hemoglobin A1c (HbA1c). This risk remained statistically significant after controlling for age, hypertension, initial National Institutes of Health Stroke Scale (NIHSS) score, HbA1c, fibrinogen and homocysteine. The serum eGFRCysC levels were significantly lower in the poor functional outcome group than the good functional outcome group (P<0.001). Multivariate logistic regression analyses showed that eGFRCysC level was significantly lower in the poor outcome group after adjusting for age, previous infarctions, initial NIHSS score, and HbA1c. CONCLUSIONS: Lower eGFRCysC levels were strongly associated with poor functional outcome of acute BSI patients with a higher HbA1c level. Lower eGFRCysC may be a more helpful serologic biomarker for the prediction of prognosis in BSI.

[Clinical features and lymphocyte subtypes in patients with IgG4-related diseases].

Objective: To deepen understanding of IgG4-related diseases (RDs), we analyzed the associated lymphocyte subtypes, and explored the pathogenesis and potential immunotherapeutic targets. Methods: Eighty-six patients with IgG4-RDs were enrolled, and their clinical characteristics, peripheral lymphocyte subtypes, and disease course were analyzed. Results: The mean age of the participants was 36-87(62±11) years; 51 were male (59.3%) and 35 were women (40.7%); and 34.9% had a history of allergy. Follow-up lasted 4.8 (0.4, 14.1) months. The most common symptoms were abdominal pain, and submandibular gland and lacrimal gland swelling (each 20.9%). Sixty-five (75.6%) participants had multiple organ involvement, and the most frequently affected organs were the pancreas (52.3%), submandibular gland (51.2%), and lacrimal gland (34.9%). A high eosinophil count; high IgE, IgG, IgG1, and IgG4 concentrations; and low complement C3 and C4 concentrations were present in 18.8% (16/85), 30.0% (24/80), 72.9% (62/85), 58.3% (28/48), 89.5% (77/86), 61.2% (52/85), and 50.0% (42/84), respectively, of the participants. In addition, 64.7% (55/85) were positive for autoantibodies, and the most frequent was anti-nuclear antibody (63.5%). The proportion of CD4+T lymphocytes increased in 25.7% (9/35) of the participants, which was accompanied by an increase in the ratio of CD4+/CD8+T lymphocytes (22.9%, 8/35). Importantly, most participants (90.0%, 18/20) had a high proportion of regulatory T (Treg) cells. High interleukin (IL)-2, IL-6, and IL-10 concentrations were present in 50.0% (11/22), 33.3% (10/30), and 16.7% (5/30), respectively, of the participants. Substantial lymphoplasmacytic infiltration, fibrosis, IgG4-positive plasma cell infiltration, and lymphoid follicle hyperplasia or ectopic formation were present in 79.2% (42/53), 67.9%(36/53), 35.8%(19/53) and 30.2% (16/53), respectively, of the participants. Fifty-three participants with detailed pathologic data were also further evaluated, of whom 24.5% (13/53), 3.8% (2/53), and 67.9% (36/53) had definite, probable, and possible diagnoses; and 3.8% (2/53) could not be diagnosed. Compared with baseline, the percentage of eosinophils and the IgE, IgG, and IgG4 concentrations decreased significantly; and the complement C3 and C4 concentrations had increased significantly after 6 months of treatment (all P<0.05). The IgG4 concentration after 6 months of treatment negatively correlated with that of C4, and positively correlated with the baseline concentration of IgE and the IgG4/IgG ratio. Conclusion: IgG4-RDs are a group of diseases characterized by male predisposition; multiple organ involvement; a high eosinophil count; high IgE, IgG, IgG1, and IgG4 concentrations; and a low C3 concentration. Peripheral CD4+T cells and Treg cells are also more abundant. The diseases can be controlled with glucocorticoids and immunosuppressive drugs in the majority of instances. The IgG4 concentration after 6 months of treatment negatively correlates with the baseline complement C4 concentration and positively correlates with the IgE concentration and IgG4/IgG ratio, which suggests that IgG4/IgG, IgE, and complement should be closely monitored to evaluate disease activity and the efficacy of treatment in such patients.

[The application of induction chemotherapy in the treatment of locally advanced head and neck squamous cell carcinoma].

Standard treatment for patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) whose larynx could not be preserved surgically consists mainly of concurrent chemoradiotherapy (CCRT). Induction chemotherapy (ICT) followed by radiotherapy or chemoradiotherapy is also an alternative option. However, whether ICT could provide survival benefits for patients with LAHNSCC, besides its role in laryngeal preservation and selecting the treatment modality, is still controversial. The article summarizes the current position of ICT for LAHNSCC and discusses the standard regimen of ICT, its role in larynx preservation, its ability to predicting the result of chemoradiotherapy, clinical outcomes regarding the survival benefits after ICT, its role in the treatment deintensification for human papillomavirus-positive LAHNSCC and its application in the era of immunotherapy.

[Comparison of the efficacy of carelizumab combined with chemotherapy and chemotherapy alone in the induction therapy of locally advanced hypopharyngeal carcinoma].

Objective: To compare the efficacy and safety of carrelizumab combined with the modified TPF regimen (docetaxel, cisplatinand capecitabine) and TPF regimen alone in larynx preservation strategy for locally advanced resectable hypopharyngeal squamous cell carcinoma. Methods: A cohort study was conducted. Patients with locally advanced resectable hypopharyngeal carcinoma (cT3-4aN0-3bM0) who were treated at the Eye & ENT Hospital of Fudan University from January 2017 to April 2023 were enrolled in the study. One group was treated with a modified TPF regimen (TPF group) for 2-3 cycles (retrospective data), and the other group was a prospective phase Ⅱ trial with a modified TPF regimen combined with carrelizumab (TPFC group) for three cycles. The patients with complete or partial remission of the primary focus were treated with sequential radical radiotherapy and/or drug therapy. The patients in the TPFC group were treated with carrelizumab at the end of radiotherapy with a maximum of up to 18 doses. The patients with stable or progressive disease were given radical surgery, and those who refused the surgery were given radical chemoradiotherapy. Objective response rate (ORR), overall survival rate, progression-free survival (PFS) rate, larynx preservation rate (LPR), and adverse reactions were compared between the two groups. Results: There were 51 male patients in the TPFC group, with an median age of 57 (35, 69) years. Meanwhile, 44 patients were in the TPF group, among which 43 were male and one was female, with an median age of 62 (46, 70) years. The ORR of the TPFC group was higher than that of the TPF group [82.4% (42/51) vs 63.6% (28/44), P=0.039]. During a median follow-up of 24.4 (18.5, 31.4) months, the TPFC group showed a higher 2-year survival rate (84.8% vs 64.6%, P=0.013) and 2-year LPR (66.6% vs 48.6%, P=0.045) than those in the TPF group. In patients with poor effect of induction therapy for hypopharyngeal carcinoma, surgical combination therapy significantly prolonged the 2-year PFS rate (77.9% vs 18.2%, P<0.001) and 2-year survival rate (76.9% vs 45.5%, P=0.005)than those of non-surgical combination therapy. The incidences of nausea and/or vomiting, reactive cutaneous capillary endothelial proliferation, thyroid dysfunction, and rash were increased in the TPFC group (all P<0.05). There was no treatment-related death. Conclusion: Carrelizumab combined with a modified TPF regimen has good efficacy and safety and can improve the LPR of locally advanced hypopharyngeal carcinoma.

[Clinical characteristics and associated factors of mild cognitive impairment in patients with common cardiovascular diseases].

Objective: To analyze the clinical characteristics of patients with common cardiovascular diseases (CVD, including hypertension, coronary heart disease, atrial fibrillation, and heart failure) combined with mild cognitive impairment (MCI) and explore the potential risk factors of MCI in patients with CVD. Methods: A total of 2 294 patients with common cardiovascular diseases who met the criteria at Cardiology Medical Center in Beijing Anzhen Hospital, Capital Medical University, from June 1, 2021, to January 5, 2022, were retrospectively included. The patients were divided into the normal cognitive function group (1 107 cases) and the MCI group (1 187 cases). Demographic information and CVD status were collected. The information of cognitive function were collected using the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) scales. The difference between normal cognitive function and MCI were compared and analyzed. The logistic regression analysis was used to explored risk factors of MCI in CVD patients. Results: A total of 2 294 patients aged (60.6±10.4) years were included, among whom there were 29.99% (688 cases) females. Compared with patients in the normal cognitive function group, patients in the MCI group were older [ (57.9±11.4) vs (63.1±8.9) years old, P<0.001], with a higher proportion of women [26.47% (293 cases) vs 33.28% (395 cases), P<0.001]; there was a higher proportion of patients suffering from hypertension in the MCI group [59.62% (660 cases) vs 64.62% (767 cases), P=0.014ï¼½, and more components of CVD [(1.68±0.62) vs (1.74±0.65) components, P=0.017]. The risk factors of MCI in patients with common CVD were increased age, increased depression score, combined with hypertension, and ≥3 common components of CVD, with OR (95%CI) of 1.043 (1.032-1.054), 1.021 (1.004-1.037), 1.151 (1.142-3.439), and 1.137 (1.023-1.797), respectively (all P values <0.05). Increasing education level was observed to be associated with reduced risk of MCI with OR (95%CI) of 0.319 (0.271-0.378) (P<0.05). Conclusions: The incidence of MCI was high in CVD patients. The risk factors of MCI in CVD patients included hypertension and≥3 common components of CVD.

[Development and validation of a persistent postural-perceptual dizziness screening questionnaire].

Objective: To develop a simple screening questionnaire for persistent postural-perceptual dizziness (PPPD) and evaluate its screening ability. Methods: A convenience sample of 296 individuals who met the inclusion criteria between November 2021 and January 2023 were prospectively selected for three rounds of screening at the Vertigo Specialty Clinic of the Department of Otorhinolaryngology-Head and Neck Surgery in the First Hospital of Shanxi Medical University. In conjunction with expert opinion and statistical analysis, the first and second rounds of screening were used to modify and finalize the questionnaire entries, and the third round of screening was used to evaluate the questionnaire's screening ability. Independent sample t-test was used for inter group comparison, reliability and validity indicators were employed to screen and evaluate questionnaire entries, and the receiver operating characteristic (ROC) curve was plotted to determine the optimal cut-off value and corresponding sensitivity and specificity. Results: The final PPPD screening questionnaire entries included 21 items. In evaluating the reliability of this questionnaire, the Cronbach's alpha coefficient was 0.831, the half folding coefficient was 0.742, the content validity was 0.86, and the Kaiser-Meyer-Olkin (KMO) value in the structural validity was 0.811. Additionally, there were six factors with characteristic root>1 and a cumulative contribution rate of 62.62%. The area under the ROC curve of the screening questionnaire was 0.935 (95%CI: 0.877-0.992), and the optimal cut-off value was 8.5, with a sensitivity of 85.0%, a specificity of 85.5%, and a Kappa value of 0.653. Conclusion: The PPPD simple screening questionnaire designed in this study has a high sensitivity and specificity, making it a useful tool for identifying PPPD patients.

[Advances in the construction of risk prediction models for chronic kidney failure].

Chronic kidney disease (CKD) is a major public health problem worldwide. When CKD patients progress to the stage of kidney failure, kidney replacement therapy (KRT) or conservative treatment (palliative or non-dialysis treatment) will be needed. The risk prediction models of chronic kidney failure have been developed in recent years. These models, focusing on demographic indicators, clinical indicators, and laboratory data, are used to predict the likelihood of progression to kidney failure and requiring KRT. This article will retrieve prediction models for chronic kidney failure as an outcome, demonstrate the current research progress, and hope that it may be helpful for the strategies of preventing chronic kidney failure.

[Randomized controlled study on the application effect of a new type of intravenous radiofrequency closed therapy system made in China and an imported system].

Objective: To compare the application effect of domestic and imported intravenous radiofrequency closure system in the treatment of primary varicose veins of lower extremities. Methods: This single-center prospective, non-inferiority randomized controlled trial was performed in the Department of Vascular Surgery, the Fourth Affiliated Hospital, Zhejiang University School of Medicine from January 2021 to January 2022. Patients with primary varicose veins of lower extremities who met the ataxation criteria were randomly assigned to the experimental group(domestic novel venous radiofrequency closure system) or the control group(imported venous radiofrequency closure system) in a ratio of 1∶1. The two groups of subjects were compared in terms of target vein closure rate, technical success rate, system operation performance, incidence of adverse events and incidence of serious adverse events(SAE) within 6 months after surgery. Quantitative data were compared by Mann-Whitney U test, and categorical data were compared by χ2 test and non-inferiority test. Results: A total of 80 subjects were included in the trial (41 in the experimental group and 39 in the control group), including 27 males and 53 females, aged (M(IQR)) 55(23) years (range:40 to 78 years). There were 48 cases of left lower limb and 32 cases of right lower limb. The technical success rate and system control performance between the groups were 100%.The incidence of adverse events (58.5% (24/41) vs. 61.5% (24/39), χ2=0.075, P=0.784), and the incidence of SAE (7.3% (3/41) vs. 5.1% (2/39), χ2=0.163, P=0.686) within 6 months after surgery in experimental group and control group had no statistical significance. There was one device-related adverse event in each of the two groups. In the experimental group, one patient developed endovenous heat-induced thrombosis after surgery and recovered after taking rivaroxaban tablets. One patient in the control group had pain in the upper right thigh for more than 1 day after operation, which was cured after using analgesic cream. No device-related SAE occurred. The venous closure rate of the experimental group was 100% (38/38) at 6 months after surgery, and that of the control group was 97.4% (37/38). The difference between the two groups was 2.63% (95%CI:-3.19 to 8.45, Z=4.865, P<0.01), and the 95%CI lower limit of the difference in target venous closure rate between two groups was greater than the non-inferiority threshold of -10.00%. Conclusion: The early application effect of the new domestic intravenous radiofrequency closure system in patients with primary varicose veins of lower extremities is in line with expectations, it is not inferior to the imported system.

[Analysis of disease burden of welder's pneumoconiosis in Jiangsu Province].

Objective: To investigate the current status of disease burden and its influencing factors among welder's pneumoconiosis patients, and provide scientific basis for taking targeted intervention measures. Methods: From June 2022 to June 2023, the patients with welder's pneumoconiosis in Jiangsu Province were selected from 1956 to 2020 as the research objects, and disability adjusted life years (DALY) were used as the comprehensive index to study the disease burden. The direct and indirect economic losses caused by the diseases were calculated, and the factors affecting the disease burden were discussed by multiple linear regression method. Results: A total of 974 cases of welder's pneumoconiosis were reported in Jiangsu Province, the cumulative loss of DALY was 6300.73 person-years, and the per capita loss was 6.47 person-years. Among them, the healthy life years lost due to disability (YLD) was 6156.50 person-years (97.71%) , and the healthy life years lost due to premature death (YLL) was 144.23 person-years (2.29%) . Multiple linear regression analysis showed that the main factors affecting DALY were disability grade, diagnostic age, pneumoconiosis grade and length of dust exposure (P<0.05) . The total economic loss caused by 974 welder's pneumoconiosis patients was 1831838160.18 yuan, and the per capita loss was 1880737.33 yuan. Among them, the direct economic loss was 970917563.75 yuan (53.00%) , and the indirect economic loss was 860920596.43 yuan (47.00%) . Conclusion: Welder's pneumoconiosis causes serious disease burden to patients, and at the same time causes huge economic losses to individuals and society, which seriously hinders the development of society. Taking effective control measures to prevent the incidence of welder's pneumoconiosis is the key to reduce the disease burden.

Octahedral Distortion and Displacement-Type Ferroelectricity with Switchable Photovoltaic Effect in a 3d

Because of the half-filled t_{2g}-electron configuration, the BO_{6} octahedral distortion in a 3d^{3} perovskite system is usually very limited. In this Letter, a perovskitelike oxide Hg_{0.75}Pb_{0.25}MnO_{3} (HPMO) with a 3d^{3} Mn^{4+} state was synthesized by using high pressure and high temperature methods. This compound exhibits an unusually large octahedral distortion enhanced by approximately 2 orders of magnitude compared with that observed in other 3d^{3} perovskite systems like RCr^{3+}O_{3} (R=rare earth). Essentially different from centrosymmetric HgMnO_{3} and PbMnO_{3}, the A-site doped HPMO presents a polar crystal structure with the space group Ama2 and a substantial spontaneous electric polarization (26.5 µC/cm^{2} in theory) arising from the off-center displacements of A- and B-site ions. More interestingly, a prominent net photocurrent and switchable photovoltaic effect with a sustainable photoresponse were observed in the current polycrystalline HPMO. This Letter provides an exceptional d^{3} material system which shows unusually large octahedral distortion and displacement-type ferroelectricity violating the "d^{0}-ness" rule.

Nomogram for evaluating coronary revascularisation necessity based on multi-parameter coronary CT angiography.

AIM: To build a nomogram model to improve the evaluation of revascularisation necessity using multi-parameter coronary computed tomography (CT) angiography (CCTA). MATERIALS AND METHODS: In this retrospective study, 335 patients who underwent CCTA and required revascularisation within 1 month were selected and allocated to the revascularisation group; 208 patients who did not undergo revascularisation were allocated to the non-revascularisation group. CCTA parameters, including CCTA stenosis, plaque qualitative-quantitative characteristics, and fractional flow reserve derived from CT angiography (CT-FFR), for both groups were analysed and compared. Independent risk factors for evaluating revascularisation were obtained using univariate and multivariable regression analysis, after which multi-parameter models were built. Finally, a nomogram was created with these independent risk factors using the R programming language. RESULTS: Plaque analysis was performed successfully for 543 patients with 1,072 target plaques. The performance of the multi-parameter model (AUC 0.894, p<0.001) was significantly higher than that of models based on stenosis (AUC 0.804, p<0.001), plaque qualitative/quantitative characteristics (AUC 0.754/0.789, p<0.001), or CT-FFR (AUC 0.848, p<0.001) alone, to evaluate the necessity of revascularisation. The independent risk factors were CCTA stenosis (OR 1.004, p=0.04), positive remodelling (OR 2.474, p<0.001), total plaque volume (OR 1.001, p<0.001), non-calcified plaque volume proportion (OR 1.019, p<0.001), and CT-FFR (OR 0.001, p<0.001). Subsequently, a nomogram based on these factors was created. CONCLUSION: The multi-parameter CCTA model improved performance in evaluating revascularisation necessity. The nomogram based on these factors is shows promise in clinical settings.

A dual-centre study on the radioprotective effect of a novel X-ray protection device during coronary intervention.

AIM: To investigate the shielding efficiency of a novel X-ray protection device (NPD) compared with the traditional lead clothing (TLC) during coronary intervention. MATERIALS AND METHODS: This study was performed prospectively in two centres. A total of 200 coronary interventions were included and assigned equally into the NPD or TLC group. The NPD is a floor-standing X-ray protection device, which mainly composes of a barrel-like frame and two layers of lead rubber. Thermoluminescent dosimeters (TLDs) were adopted to detect the cumulative absorbed doses, and were attached outside the NPD or TLC or body of the first operator at four different height levels in four directions during the procedure. RESULTS: The cumulative doses outside the NPD were comparable to that of the TLC (2,398.33 ± 2,341.64 versus 1,624.09 ± 1,732.20 µSv, p=0.366), and the cumulative doses inside the NPD were significantly lower than those inside the TLC (40 ± 0 versus 732.28 ± 919.83 µSv, p<0.001). As the TLC did not cover the calf segment of the operator, the area at 50 cm height from the floor in the TLC group was unshielded. The shielding efficiency of NPD was significantly higher than that of the TLC (98.2 ± 0.63% versus 52.11 ± 38.97%, p=0.021). CONCLUSION: The NPD has a significantly higher shielding efficacy than that of the TLC, in particular, it protects the operators' lower limb, liberates their lower body from wearing heavy lead apron, and may consequently reduce the radiation or body-load associated complications.

Genetically elevated bioavailable testosterone level was associated with the occurrence of benign prostatic hyperplasia.

BACKGROUND: Recent studies identified several risk factors of benign prostatic hyperplasia (BPH), including dyslipidemia, type 2 diabetes mellitus, hypertension, and obesity. But they were not so reliable and some studies contradicted with one another. Hence, a reliable method is urgently needed to explore exact factors that facilitated BPH development. METHODS: The study was based on Mendelian randomization (MR) design. All participants were from the most recent genome-wide association studies (GWAS) with large sample size. The causal associations between nine phenotypes (total testosterone level, bioavailable testosterone level, sex hormone-binding globulin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, type 2 diabetes mellitus, hyper-tension, and body mass index) and BPH outcome were estimated. Two sample MR, bidirectional MR, and multivariate MR (MVMR) were performed. RESULTS: Increase in bioavailable testosterone level was able to induce BPH based on nearly all combination methods [beta (95% confidence interval (CI)): 0.20 (0.06-0.34) for inverse variance weighted (IVW)]. The other traits seemed to interact with testosterone level and did not cause BPH generally. Higher triglycerides level was likely to raise bioavailable testosterone level [beta (95% CI): 0.04 (0.01-0.06) for IVW]. In MVMR model, bioavailable testosterone level was still associated with BPH occurrence [beta (95% CI) 0.27 (0.03-0.50) for IVW]. CONCLUSIONS: We for the first time validated the central role of bioavailable testosterone level in the pathogenesis of BPH. The complex associations between other traits and BPH should be further investigated.

Identification of potential diagnostic and prognostic biomarkers for papillary thyroid microcarcinoma (PTMC) based on TMT-labeled LC-MS/MS and machine learning.

OBJECTIVES: To explore the molecular mechanisms underlying aggressive progression of papillary thyroid microcarcinoma and identify potential biomarkers. METHODS: Samples were collected and sequenced using tandem mass tag-labeled liquid chromatography-tandem mass spectrometry. Differentially expressed proteins (DEPs) were identified and further analyzed using Mfuzz and protein-protein interaction analysis (PPI). Parallel reaction monitoring (PRM) and immunohistochemistry (IHC) were performed to validate the DEPs. RESULTS: Five thousand, two hundred and three DEPs were identified and quantified from the tumor/normal comparison group or the N1/N0 comparison group. Mfuzz analysis showed that clusters of DEPs were enriched according to progressive status, followed by normal tissue, tumors without lymphatic metastases, and tumors with lymphatic metastases. Analysis of PPI revealed that DEPs interacted with and were enriched in the following metabolic pathways: apoptosis, tricarboxylic acid cycle, PI3K-Akt pathway, cholesterol metabolism, pyruvate metabolism, and thyroid hormone synthesis. In addition, 18 of the 20 target proteins were successfully validated with PRM and IHC in another 20 paired validation samples. Based on machine learning, the five proteins that showed the best performance in discriminating between tumor and normal nodules were PDLIM4, ANXA1, PKM, NPC2, and LMNA. FN1 performed well in discriminating between patients with lymph node metastases (N1) and N0 with an AUC of 0.690. Finally, five validated DEPs showed a potential prognostic role after examining The Cancer Genome Atlas database: FN1, IDH2, VDAC1, FABP4, and TG. Accordingly, a nomogram was constructed whose concordance index was 0.685 (confidence interval: 0.645-0.726). CONCLUSIONS: PDLIM4, ANXA1, PKM, NPC2, LMNA, and FN1 are potential diagnostic biomarkers. The five-protein nomogram could be a prognostic biomarker.

High prevalence of vertebral deformity in tumor-induced osteomalacia associated with impaired bone microstructure.

PURPOSE: Patients with tumor-induced osteomalacia (TIO) often suffer from irreversible height loss due to vertebral deformity. However, the prevalence of vertebral deformity in TIO patients varies among limited studies. In addition, the distribution and type of vertebral deformity, as well as its risk factors, remain unknown. This study aimed to identify the prevalence, distribution, type and risk factors for vertebral deformity in a large cohort of TIO patients. METHODS: A total of 164 TIO patients were enrolled in this retrospective study. Deformity in vertebrae T4-L4 by lateral thoracolumbar spine radiographs was evaluated according to the semiquantitative method of Genant. Bone microstructure was evaluated by trabecular bone score (TBS) and high-resolution peripheral QCT (HR-pQCT). RESULTS: Ninety-nine (99/164, 60.4%) patients had 517 deformed vertebrae with a bimodal pattern of distribution (T7-9 and T11-L1), and biconcave deformity was the most common type (267/517, 51.6%). Compared with patients without vertebral deformity, those with vertebral deformity had a higher male/female ratio, longer disease duration, more height loss, lower serum phosphate, higher bone turnover markers, lower TBS, lower areal bone mineral density (aBMD), lower peripheral volumetric BMD (vBMD) and worse microstructure. Lower trabecular vBMD and worse trabecular microstructure in the peripheral bone and lower spine TBS were associated with an increased risk of vertebral deformity independently of aBMD. After adjusting for the number of deformed vertebrae, we found little difference in clinical indexes among the patients with different types of vertebral deformity. However, we found significant correlations of clinical indexes with the number of deformed vertebrae and the spinal deformity index. CONCLUSION: We reported a high prevalence of vertebral deformity in the largest cohort of TIO patients and described the vertebral deformity in detail for the first time. Risk factors for vertebral deformity included male sex, long disease duration, height loss, abnormal biochemical indexes and bone impairment. Clinical manifestation, biochemical indexes and bone impairment were correlated with the number of deformed vertebrae and degree of deformity, but not the type of deformity.

Association of radiotherapy for prostate cancer and second primary colorectal cancer: a US population-based analysis.

BACKGROUND: Radiotherapy (RT) is a common treatment for prostate cancer, yet the risk of second primary colorectal cancer (SPCRC) in patients with prostate cancer undergoing RT has not been adequately studied. METHODS: This study employed a population-based cohort design using the US Surveillance, Epidemiology, and End Results (SEER) database to identify individuals diagnosed between January 1975 and December 2015. The cumulative incidence of SPCRC was estimated using Fine-Gray competing risk regression. Poisson regression analysis was used to estimate the risk associated with RT. Survival outcomes of patients with SPCRC were evaluated using the Kaplan-Meier method. RESULTS: A total of 287,607 patients diagnosed with prostate cancer were identified. The cumulative incidences were higher in patients who did not receive RT (2.00%) compared to those who underwent RT (2.47%) after 25 years. After adjustment for multiple variables, RT was associated with an increased risk of developing combined SPCRC (adjusted HR 1.590). Additionally, the overall survival was significantly lower in patients who developed colorectal cancer after receiving RT as compared to those who did not receive RT. CONCLUSION: These findings underscore the need for diligent long-term monitoring and effective management strategies to detect SPCRC in patients treated with RT for prostate cancer.

[The performance of digital chest radiographs in the detection and diagnosis of pulmonary nodules and the consistency among readers].

Objective: To investigate the detection and diagnostic efficacy of chest radiographs for ≤30 mm pulmonary nodules and the factors affecting them, and to compare the level of consistency among readers. Methods: A total of 43 patients with asymptomatic pulmonary nodules who consulted in Cancer Hospital, Chinese Academy of Medical Sciences from 2012 to 2014 and had chest CT and X-ray chest radiographs during the same period were retrospectively selected, and one nodule ≤30 mm was visible on chest CT images in the whole group (total 43 nodules in the whole group). One senior radiologist with more than 20 years of experience in imaging diagnosis reviewed CT images and recording the size, morphology, location, and density of nodules was selected retrospectively. Six radiologists with different levels of experience (2 residents, 2 attending physicians and 2 associate chief physicians independently reviewed the chest images and recorded the time of review, nodule detection, and diagnostic opinion. The CT imaging characteristics of detected and undetected nodules on X images were compared, and the factors affecting the detection of nodules on X-ray images were analyzed. Detection sensitivity and diagnosis accuracy rate of 6 radiologists were calculated, and the level of consistency among them was compared to analyze the influence of radiologists' seniority and reading time on the diagnosis results. Results: The number of nodules detected by all 6 radiologists was 17, with a sensitivity of detection of 39.5%(17/43). The number of nodules detected by ≥5, ≥4, ≥3, ≥2, and ≥1 physicians was 20, 21, 23, 25, and 28 nodules, respectively, with detection sensitivities of 46.5%, 48.8%, 53.5%, 58.1%, and 65.1%, respectively. Reasons for false-negative result of detection on X-ray images included the size, location, density, and morphology of the nodule. The sensitivity of detecting ≤30 mm, ≤20 mm, ≤15 mm, and ≤10 mm nodules was 46.5%-58.1%, 45.9%-54.1%, 36.0%-44.0%, and 36.4% for the 6 radiologists, respectively; the diagnosis accuracy rate was 19.0%-85.0%, 16.7%-6.5%, 18.2%-80.0%, and 0%-75.0%, respectively. The consistency of nodule detection among 6 doctors was good (Kappa value: 0.629-0.907) and the consistency of diagnostic results among them was moderate or poor (Kappa value: 0.350-0.653). The higher the radiologist's seniority, the shorter the time required to read the images. The reading time and the seniority of the radiologists had no significant influence on the detection and diagnosis results (P>0.05). Conclusions: The ability of radiographs to detect lung nodules ≤30 mm is limited, and the ability to determine the nature of the nodules is not sufficient, and the increase in reading time and seniority of the radiologists will not improve the diagnostic accuracy. X-ray film exam alone is not suitable for lung cancer diagnosis.