Is prone free breathing better than supine deep inspiration breath-hold for left whole-breast radiotherapy? A dosimetric analysis.

PURPOSE: The advantage of prone setup compared with supine for left-breast radiotherapy is controversial. We evaluate the dosimetric gain of prone setup and aim to identify predictors of the gain. METHODS: Left-sided breast cancer patients who had dual computed tomography (CT) planning in prone free breathing (FB) and supine deep inspiration breath-hold (DiBH) were retrospectively identified. Radiation doses to heart, lungs, breasts, and tumor bed were evaluated using the recently developed mean absolute dose deviation (MADD). MADD measures how widely the dose delivered to a structure deviates from a reference dose specified for the structure. A penalty score was computed for every treatment plan as a weighted sum of the MADDs normalized to the breast prescribed dose. Changes in penalty scores when switching from supine to prone were assessed by paired t-tests and by the number of patients with a reduction of the penalty score (i.e., gain). Robust linear regression and fractional polynomials were used to correlate patients' characteristics and their respective penalty scores. RESULTS: Among 116 patients identified with dual CT planning, the prone setup, compared with supine, was associated with a dosimetric gain in 72 (62.1%, 95% CI: 52.6-70.9%). The most significant predictors of a gain with the prone setup were the breast depth prone/supine ratio (>1.6), breast depth difference (>31 mm), prone breast depth (>77 mm), and breast volume (>282 mL). CONCLUSION: Prone compared with supine DiBH was associated with a dosimetric gain in 62.1% of our left-sided breast cancer patients. High pendulousness and moderately large breast predicted for the gain.

Predictive value of D-dimer and analysis of risk factors in pregnant women with suspected pulmonary embolism after cesarean section.

BACKGROUND: Acute pulmonary embolism (PE) is one of the leading causes of maternal mortality, and cesarean section is an established independent risk factor for PE. The diagnostic utility of D-dimer for PE in non-pregnant women has been well-established, but its role in women with suspected PE after cesarean section is unclear. Furthermore, the optimal threshold level in this patient population is unknown. Traditional D-dimer levels have low diagnostic specificity, resulting in many pregnant women being exposed to potentially harmful radiation despite negative diagnostic imaging results. This research aimed to optimize the clinical threshold for D-dimer to improve specificity while ensuring high sensitivity and to identify risk factors for PE after cesarean section. METHODS: This retrospective study of 289 women who underwent diagnostic imaging (ventilation/perfusion [V/Q] or computed tomographic pulmonary angiography [CTPA]) for suspected acute PE after cesarean delivery from 2010 to 2021 was conducted. Clinical data and laboratory indicators within 24 h postpartum including D-dimer levels were collected for analyses. RESULTS: The final analysis included 125 patients, among whom 33 were diagnosed with acute PE (incidence of 11.42%, 95% confidence interval 7.7-15.1). The receiver operating characteristic curve analysis suggested that a D-dimer cut-off value of 800 ng/mL had specificity of 25.26% and sensitivity of 100% for detecting PE. The cut-off value was adjusted to 1000 ng/mL with a specificity of 34.74% and a sensitivity of 96.67%. Using a D-dimer cut-off value of 800 ng/mL (instead of the conventional value of 500 ng/mL) increased the number of patients excluded from suspected PE from 9.6 to 18.4% without additional false-negative results. Of note, a history of known thrombophilia was significantly more common in patients with PE than in those without (P < 0.05). No other independent risk factors were noted in our study. CONCLUSIONS: The D-dimer cut-off value of 800 ng/mL ensures high sensitivity and increases specificity compared to the conventional threshold of 500 ng/mL. Utilizing this higher threshold can reduce the number of unnecessary CT and subsequently unnecessary radiation exposure, in women after cesarean delivery. Prospective studies should also be conducted to verify these results.

Astragaloside IV attenuates chronic intermittent hypoxia-induced myocardial injury by modulating Ca2+ homeostasis.

Obstructive sleep apnea syndrome (OSAS) is an important consequence of chronic intermittent hypoxia (CIH). Astragaloside IV (AS-IV) exerts multiple protective effects in diverse diseases. However, whether AS-IV can attenuate CIH-induced myocardial injury is unclear. In this study, rats exposed to CIH were established and treated with AS-IV for 4 weeks. In vitro, H9C2 cardiomyocytes subjected to CIH exposure were treated with AS-IV for 48 hours. Then the cardiac function, morphology, fibrosis, apoptosis and Ca2+ homeostasis were determined to assess cardiac damage. Results showed that AS-IV attenuated cardiac dysfunction and histological lesions in CIH rats. The increased TUNEL-positive cells and activated apoptotic proteins in CIH rats were reduced by AS-IV. We also noticed that AS-IV reversed the accumulation of Ca2+ and altered expressions of Ca2+ handling proteins (decreases of SERCA2a and RYR2, and increases of p-CaMKII and NCX1) under CIH exposure. Furthermore, CIH-induced reduction of SERCA2a activity was increased by AS-IV in rats. Similar results were also observed in H9C2 cells. Altogether, these findings indicate that AS-IV modulates Ca2+ homeostasis to inhibit apoptosis, protecting against CIH-induced myocardial injury eventually, suggesting it may be a potential agent for cardiac damage of OSAS patients. SIGNIFICANCE OF THE STUDY: Chronic intermittent hypoxia (CIH) is a great contributor of OSAS, which is closely associated with cardiovascular diseases. It is necessary for developing a promising drug to attenuate CIH-induced myocardial injury. This work suggests that AS-IV can attenuate myocardial apoptosis and calcium disruption, thus protecting against CIH-induced myocardial injury. It may represent a novel therapeutic for cardiac damage of OSAS.

Cloning, expression and characterization of protein disulfide isomerase of Schistosoma japonicum.

The excretory/secretory (ES) proteins of schistosomes play important roles in modulating host immune systems and are regarded as potential vaccine candidates and drug targets. Protein disulfide isomerase (PDI) is an essential enzyme that is involved in disulfide bond formation and rearrangement. In the present study, SjPDI, a 52.8 kDa protein previously identified in a proteomics analysis as one of the ES proteins of Schistosoma japonicum, was cloned and characterized. Western blot analysis showed that recombinant SjPDI (rSjPDI) was recognized by serum from rabbits vaccinated with schistosome worm antigen. Worm protein extracts and ES protein extracts from S. japonicum could react with anti-rSjPDI mouse serum. Real-time PCR analysis indicated that SjPDI was expressed at all developmental stages tested, and a high expression level was detected in 42-day-old male worms. Immunofluorescence analysis revealed that SjPDI was mainly distributed on the tegument and parenchyma of S. japonicum worms. An enzyme-linked immunosorbent assay (ELISA) demonstrated that rSjPDI could induce a high level of rSjPDI-specific IgG antibodies. The biological activity of purified rSjPDI was confirmed by isomerization and antioxidative activity assays. The 35.32%, 26.19% reduction in the worm burden and 33.17%, 31.7% lower liver egg count were obtained in mice vaccinated with rSjPDI compared with the blank control group in two independent trials. Our preliminary results suggest that rSjPDI plays an important role in the development of the schistosome and is a potential vaccine candidate for schistosomiasis.

A novel hypoglycemia alarm framework for type 2 diabetes with high glycemic variability.

In patients with type 2 diabetes (T2D), accurate prediction of hypoglycemic events is crucial for maintaining glycemic control and reducing their frequency. However, individuals with high blood glucose variability experience significant fluctuations over time, posing a challenge for early warning models that rely on static features. This article proposes a novel hypoglycemia early alarm framework based on dynamic feature selection. The framework incorporates domain knowledge and introduces multi-scale blood glucose features, including predicted values, essential for early warnings. To address the complexity of the feature matrix, a dynamic feature selection mechanism (Relief-SVM-RFE) is designed to effectively eliminate redundancy. Furthermore, the framework employs online updates for the random forest model, enhancing the learning of more relevant features. The effectiveness of the framework was evaluated using a clinical dataset. For T2D patients with a high coefficient of variation (CV), the framework achieved a sensitivity of 81.15% and specificity of 98.14%, accurately predicting most hypoglycemic events. Notably, the proposed method outperformed other existing approaches. These results indicate the feasibility of anticipating hypoglycemic events in T2D patients with high CV using this innovative framework.

The Incidence and Prevalence of Pulmonary Hypertension in the COPD Population: A Systematic Review and Meta-Analysis.

Purpose: Chronic obstructive pulmonary disease (COPD)-related pulmonary hypertension (PH) is one of the most common comorbidities of COPD, and often leads to a worse prognosis. Although the estimated prevalence and risk factors of COPD-related PH have been widely reported, these results have not been well integrated. This study aimed to review the worldwide incidence and prevalence of COPD-related PH and explore possible factors affecting its prevalence. Patients and Methods: We searched four electronic databases (Web of Science, Embase, Cochrane, and MEDLINE) to identify all observational studies on the prevalence of COPD-related PH from database creation until July 20, 2021. Eligibility screening, quality assessment, and data extraction of the retrieved studies were independently conducted by two reviewers. Meta-analyses were performed to determine the prevalence of PH in the COPD population. Random-effects meta-regression model analyses were conducted to investigate the sources of heterogeneity. Results: Altogether, 38 articles were included in the meta-analyses. The pooled prevalence was 39.2% (95% CI: 34.0-44.4, I2 = 97.6%) for COPD-related PH. Subgroup analyses showed that the prevalence of PH increased with COPD severity, where the majority (30.2%) had mild PH and the minority had severe PH (7.2%). Furthermore, we found a significant regional difference in the prevalence of COPD-related PH (P = 0.000), which was the highest in Africa (64.0%) and the lowest in Europe (30.4%). However, stratified studies on other factors involving mean age, sex, enrolment time, participant recruitment settings, and PH diagnostic methods showed no significant differences in prevalence (P >0.05). Conclusion: The global incidence of PH in the COPD population is very high, and there are significant regional and international variations. Patients with COPD should be screened for PH and contributing risk factors to reduce the burden on individuals and society.

Prone versus supine free-breathing for right-sided whole breast radiotherapy.

Prone setup has been advocated to improve organ sparing in whole breast radiotherapy without impairing breast coverage. We evaluate the dosimetric advantage of prone setup for the right breast and look for predictors of the gain. Right breast cancer patients treated in 2010-2013 who had a dual supine and prone planning were retrospectively identified. A penalty score was computed from the mean absolute dose deviation to heart, lungs, breasts, and tumor bed for each patient's supine and prone plan. Dosimetric advantage of prone was assessed by the reduction of penalty score from supine to prone. The effect of patients' characteristics on the reduction of penalty was analyzed using robust linear regression. A total of 146 patients with right breast dual plans were identified. Prone compared to supine reduced the penalty score in 119 patients (81.5%). Lung doses were reduced by 70.8%, from 4.8 Gy supine to 1.4 Gy prone. Among patient's characteristics, the only significant predictors were the breast volumes, but no cutoff could identify when prone would be less advantageous than supine. Prone was associated with a dosimetric advantage in most patients. It sets a benchmark of achievable lung dose reduction.Trial registration: ClinicalTrials.gov NCT02237469, HUGProne, September 11, 2014, retrospectively registered.

Atlas Sampling for Prone Breast Automatic Segmentation of Organs at Risk: The Importance of Patients' Body Mass Index and Breast Cup Size for an Optimized Contouring of the Heart and the Coronary Vessels.

OBJECTIVE: Delineation of organs at risk is a time-consuming task. This study evaluates the benefits of using single-subject atlas-based automatic segmentation of organs at risk in patients with breast cancer treated in prone position, with 2 different criteria for choosing the atlas subject. Together with laterality (left/right), the criteria used were either (1) breast volume or (2) body mass index and breast cup size. METHODS: An atlas supporting different selection criteria for automatic segmentation was generated from contours drawn by a senior radiation oncologist (RO_A). Atlas organs at risk included heart, left anterior descending artery, and right coronary artery. Manual contours drawn by RO_A and automatic segmentation contours of organs at risk and breast clinical target volume were created for 27 nonatlas patients. A second radiation oncologist (RO_B) manually contoured (M_B) the breast clinical target volume and the heart. Contouring times were recorded and the reliability of the automatic segmentation was assessed in the context of 3-D planning. RESULTS: Accounting for body mass index and breast cup size improved automatic segmentation results compared to breast volume-based sampling, especially for the heart (mean similarity indexes >0.9 for automatic segmentation organs at risk and clinical target volume after RO_A editing). Mean similarity indexes for the left anterior descending artery and the right coronary artery edited by RO_A expanded by 1 cm were ≥0.8. Using automatic segmentation reduced contouring time by 40%. For each parameter analyzed (eg, D2%), the difference in dose, averaged over all patients, between automatic segmentation structures edited by RO_A and the same structure manually drawn by RO_A was <1.5% of the prescribed dose. The mean heart dose was reliable for the unedited heart segmentation, and for right-sided treatments, automatic segmentation was adequate for treatment planning with 3-D conformal tangential fields. CONCLUSIONS: Automatic segmentation for prone breast radiotherapy stratified by body mass index and breast cup size improved segmentation accuracy for the heart and coronary vessels compared to breast volume sampling. A significant reduction in contouring time can be achieved by using automatic segmentation.

Automatic segmentation of breast in prone position: Correlation of similarity indexes and breast pendulousness with dose/volume parameters.

This study evaluates edited/reviewed automatically-segmented structures of the breast target in patients planned in prone position and their dose/volume effects. Contouring times were reduced using automatic-segmentation. Similarity-indexes and pendulousness showed that targets with Dice values over 0.965 and high pendulousness, presented the best dosimetric results.

[Cloning, expression and immuno-protection analysis of a gene encoding troponin T of Schistosoma japonicum (SjTnT)].

OBJECTIVE: To clone cDNA encoding troponin T of Schistosoma japonicum (SjTnT), and evaluate the protective efficacy induced by recombinant SjTnT in BALB/c mice against S. japonicum challenge infection. METHODS: The SjTnT gene was amplified from 28-day-schistosome cDNAs by PCR and then subcloned into pET28a(+). The recombinant SjTnT protein (rSjTnT) was expressed in Escherichia coli BL21 (DE3) cells. The serum specific to rSjTnT was prepared by immunized BALB/c mice with the recombinant antigen, and the immunogenicity of rSjTnT was detected by Western blotting and ELISA. The immuno-protective efficacy induced by rSjTnT in BALB/c mice was evaluated according to the reduction in worm and egg counts. RESULTS: The cDNA encoding SjTnT was successfully cloned and expressed in E. coli. Western blotting showed that rSjTnT had a good immunogenicity. The high level of specific IgG antibodies was detected, and 33.89% worm reduction and 43.94% liver egg reduction were obtained in mice vaccinated with rSjTnT combined with Seppic 206 adjuvant compared with those in the adjuvant control group. CONCLUSIONS: rSjTnT could induce partial immuno-protection against S. japonicum infection in BALB/c mice. This study provided a basic for understanding the biological function of SjTnT.

Inhibiting TGFß1 has a protective effect on mouse bone marrow suppression following ionizing radiation exposure in vitro.

Ionizing radiation (IR) causes not only acute tissue damage but also residual bone marrow (BM) suppression. The induction of residual BM injury is primarily attributable to the induction of reactive oxygen species (ROS) pressure in hematopoietic cells. In this study, we examined if SB431542, a transforming growth factor ß1 (TGFß1) inhibitor, can mitigate IR-induced BM suppression in vitro. Our results showed that treatment with SB431542 protected mice bone marrow mononuclear cells (BMMNCs), hematopoietic progenitor cells (HPCs) and hematopoietic stem cells (HSCs) from IR-induced suppression using cell viability assays, clonogenic assays and competitive repopulation assays. Moreover, expression of gene-related ROS production in hematopoietic cells was analyzed. The expression of NOX1, NOX2 and NOX4 was increased in irradiated BMMNCs, and that of NOX2 and NOX4 was reduced by SB431542 treatment. Therefore, the results from this study suggest that SB431542, a TGFß1 inhibitor, alleviates IR-induced BM suppression at least in part via inhibiting IR-induced NOX2 and NOX4 expression.

Extrathoracic malignant peripheral nerve sheath tumor of the lateral chest wall locally recurred and metastasized to peritoneum: Report of a case.

Malignant peripheral nerve sheath tumors (MPNSTs) are rare, with an expected incidence of 0.0001% per year in the general population and 4.6% in patients with von Recklinghausen's disease. They are defined as any malignant tumors arising or differentiating from cells of the peripheral nerve sheath. MPNSTs can develop in various sites including the trunk and head/neck region. However, its onset on the chest wall is very rare. Here we report a case of MPNST growing outside the thorax on the chest wall. The patient developed a local recurrence twice, which caused multiple metastases to the lung and peritoneum.

Serum zinc status and Helicobacter pylori infection in gastric disease patients.

The role of Helicobacter pylori status and serum zinc value in gastric disease patients and healthy controls were investigated. Cases used in this work were 45 gastric cancer patients, 44 with peptic ulcers, 52 suffering gastritis and 64 healthy controls, all diagnosed histologically with the controls undergoing medical checkups. Helicobacter pylori status and serum levels of Zn were determined by 13C-urea breath test and flame atomic absorption spectrophotometer, respectively. Our study showed that Helicobacter pylori infection has no change in gastritis, peptic ulcer and gastric cancer group, on the contrast, serum levels of Zn were significantly reduced in gastritis, peptic ulcer and gastric cancer group, compared with healthy controls, and the higher the Zn levels are, the more increased risk of gastric cancer. Helicobacter pylori infection is a cause of gastritis, peptic ulcers and even gastric cancer, while serum zinc level is an indicator of protection of gastric membranes against damage.

[Systematic review of studies of workplace exposure to environmental tobacco smoke and lung cancer risk].

BACKGROUND AND OBJECTIVE: It has been reported that there was a close relationship between lung cancer risk and environmental tobacco smoke at workplace. The aim of this study is to explore the relationship between workplace environmental tobacco smoke exposure and lung cancer risk among non-smoking subjects. METHODS: By searching Medline, CENTRAL (the Cochrane central register of controlled trials), EMBASE, CBM, CNKI and VIP et al, we collected both domestic and overseas published documents on workplace environmental tobacco smoke exposure and lung cancer risk. Random or fixed effect models were applied to conduct systematic review on the study results, the combined odds ratio (OR) and the 95% confidence interval (CI) were calculated as well. RESULTS: 22 reports were included into the combined analysis, which indicated that 25% lung cancer risk was increased by exposing to workplace environment tobacco smoke (OR=1.25, 95%CI: 1.13-1.39, P < 0.001). For female the increased risk was 22% (OR=1.22, 95%CI: 1.05-1.42, P=0.011). For male the increased risk was 54%, but it does not reach the statistical significance (OR=1.54, 95%CI: 0.74-3.18, P=0.247). CONCLUSIONS: Workplace environmental tobacco smoke exposure is an important risk factor of lung cancer risk among non-smoking subjects. Especially for non-smoking women who expose to workplace environment tobacco smoke have a close relationship with lung cancer.

[Diagnosis value of the detection of CYFRA21-1 in non-small cell lung cancer].

BACKGROUND AND OBJECTIVE: cytokeratin-19 fragment (CYFRA21-1) is a soluble protein in serum, and may be a useful circulating tumor marker. The aim of this study is to investigate the diagnostic value of the peripheral blood CYFRA21-1 in non-small cell lung cancer (NSCLC). METHODS: the levels of peripheral blood CYFRA21-1 were detected in 107 patients with NSCLC and 51 patients with benign pulmonary diseases by enzyme linked immunosorbent assay, and ROC curve was used to analyse the results. RESULTS: singificant difference of peripheral blood CYFRA21-1 levels was detected between the NSCLC group and benign pulmonary disease group (Chi-Square=47.343, P < 0.001). At the threshold of 3.3 ng/mL, sensitivity and specificity of CYFRA21-1 as a serologic marker were 74.77% and 76.47%, respectively for any cancer. ROC curve showed that the under-curve area (AUC) of CYFRA21-1 was 0.813 9. There was no significant difference of CYFRA21-1 between subtypes of NSCLC (Chi-Square=0.450, P=0.799). The peripheral blood CYFRA21-1 level was elevated significantly in the patients with extensive disease (IIIb, IV) compared with patients with limited disase (I, II, IIIb) (Chi-Square=7.057, P=0.008). CONCLUSIONS: as a tumor marker CYFRA21-1 has relative high sensitivity and specificity for the diagnosis of NSCLC. Elevated peripheral blood CYFRA 21-1 levels were usually indicated extensive disease of NSCLC.