Applications and perspectives of tumor organoids in radiobiology (Review).

Radiotherapy exhibits significant versatility and efficacy in cancer treatment, thereby playing a crucial role in the field of oncology. However, there remains an urgent need for extensive research on various aspects of radiotherapy, including target selection, damage repair and its combination with immunotherapy. Particularly, the development of in vitro models to replicate in vivo tumor lesion responses is vital. The present study provides a thorough review of the establishment and application of tumor organoids in radiotherapy, aiming to explore their potential impact on cancer treatment.

Association between plasma proteome and pulmonary heart disease: A two-stage Mendelian randomization analysis.

Pulmonary heart disease (PHD) involves altered structure and function of the right ventricle caused by an abnormal respiratory system that causes pulmonary hypertension. However, the association between changes in plasma proteomics and PHD remains unclear. Hence, we aimed to identify causal associations between genetically predicted plasma protein levels and PHD. Mendelian randomization was performed to test the target proteins associated with PHD. Summary statistics for the human plasma proteome and pulmonary heart disease were acquired from the UK Biobank (6038 cases and 426 977 controls) and the FinnGen study (6753 cases and 302 401 controls). Publicly available pQTLs datasets for human plasma proteins were obtained from a largescale genome-wide association study in the INTERVAL study. The results were validated using a case-control cohort. We first enrolled 3622 plasma proteins with conditionally independent genetic variants; three proteins (histo-blood group ABO system transferase, activating signal cointegration 1 complex subunit 1, and calcium/calmodulin-dependent protein kinase I [CAMK1]) were significantly associated with the risk of pulmonary heart disease in the UK Biobank cohort. Only CAMK1 was successfully replicated (odds ratio: 1.1056, 95% confidence interval: 1.019-1.095, p = 0.0029) in the FinnGen population. In addition, the level of CAMK1 in 40 patients with PHD was significantly higher (p = 0.023) than that in the control group. This work proposes that CAMK1 is associated with PHD, underscoring the importance of the calcium signaling pathway in the pathophysiology to improve therapies for PHD.

Endovascular repair of bilateral isolated common iliac artery aneurysms with unsuitable anatomy utilizing an aortic bifurcated unibody endograft and modified sandwich technique to preserve pelvic blood flow: a case series.

Bilateral isolated common iliac artery aneurysms (CIAAs) are rare, and endovascular repair of CIAAs has emerged as an alternative to traditional open surgical repair. The primary goal of therapy is to exclude the aneurysm sac while maintaining perfusion of at least one internal iliac artery (IIA) to prevent pelvic ischemia. Although the iliac branch device (IBD) has improved the feasibility of preserving the IIA, its applicability is limited to a specific subset of aneurysm anatomy. We present a case series of three patients with bilateral isolated CIAAs in whom preoperative CT scans revealed an absence of a landing zone, the diameter of proximal CIA diameter was less than 13.0 mm, and normal diameter of the nonaneurysmal infrarenal aorta, making it challenging to use an IBD alone or a standard bifurcated aortic endograft to provide a proximal landing zone for iliac artery stenting. To overcome the small diameter of the infrarenal aorta, we implanted an aortic bifurcated unibody endograft. Then, we utilized a balloon-expandable covered stent-graft with overdilation as a modified sandwich technique to create an "eye of the tiger" configuration to prevent gutter leakage. The final angiography performed during the procedure revealed successful exclusion of the aneurysms, with blood flow to the right IIA and no type III endoleak. During the postoperative follow-up period, no patients exhibited symptoms associated with pelvic ischemia. There were no endoleaks or sac expansions on the two-year follow-up CT scans, and all external and internal iliac graft limbs were patent. This study demonstrated that a combination of an aortic bifurcated unibody endograft and a modified sandwich technique can effectively treat bilateral isolated CIAAs with certain anatomical constraints.

Correlation between white blood cell count and intestinal resection in patients with acute mesenteric vein thrombosis.

OBJECTIVE: Acute mesenteric vein thrombosis (AMVT) is an acute abdominal disease with onset, rapid progression, and extensive intestinal necrosis that requires immediate surgical resection. The purpose of this study was to determine the risk factors for nosocomial intestinal resection in patients with AMVT. METHODS: We retrospectively analysed 64 patients with AMVT diagnosed by CTA at the Affiliated Hospital of Kunming University of Science and Technology from January 2013 to December 2021. We compared patients who underwent intestinal resection (42 patients) with those who did not undergo intestinal resection (22 patients). The area under the ROC curve was evaluated, and a forest map was drawn. RESULTS: Among the 64 patients, 6 (9.38%) had a fever, 60 (93.75%) had abdominal pain, 9 (14.06%) had a history of diabetes, 8 (12.5%) had a history of deep vein thrombosis (DVT), and 25 (39.06%) had ascites suggested by B ultrasound or CT after admission. The mean age of all patients was 49.86 ± 16.25 years. The mean age of the patients in the enterectomy group was 47.71 ± 16.20 years. The mean age of the patients in the conservative treatment group (without enterectomy) was 53.95 ± 15.90 years. In the univariate analysis, there were statistically significant differences in leukocyte count (P = 0.003), neutrophil count (P = 0.001), AST (P = 0.048), total bilirubin (P = 0.047), fibrinogen (P = 0.022) and DD2 (P = 0.024) between the two groups. The multivariate logistic regression analysis showed that admission white blood cell count (OR = 1.153, 95% CI: 1.039-1.280, P = 0.007) was an independent risk factor for intestinal resection in patients with AMVT. The ROC curve showed that the white blood cell count (AUC = 0.759 95% CI: 0.620-0.897; P = 0.001; optimal threshold: 7.815; sensitivity: 0.881; specificity: 0.636) had good predictive value for emergency enterectomy for AMVT. CONCLUSIONS: Among patients with AMVT, patients with a higher white blood cell count at admission were more likely to have intestinal necrosis and require emergency enterectomy. This study is helpful for clinicians to accurately determine whether emergency intestinal resection is needed in patients with AMVT after admission, prevent further intestinal necrosis, and improve the prognosis of patients.

Selective aneurysmal sac neck-targeted embolization during endovascular repair of abdominal aortic aneurysm with hostile neck anatomy.

PURPOSE: To evaluate the efficacy and safety of selective aneurysmal sac neck-targeted embolization in endovascular aneurysm repair (EVAR) in patients with a hostile neck anatomy (HNA). MATERIALS AND METHODS: Between October 2020 and June 2022, patients with an abdominal aortic aneurysm (AAA) and HNA who underwent EVAR with a low-profile stent graft and a selective aneurysmal sac neck-targeted embolization technique were analysed. An HNA was defined by the presence of any of the following parameters: infrarenal neck angulation > 60°; neck length < 15 mm; conical neck; circumferential calcification ≥ 50%; or thrombus ≥ 50%. Before occluding the entire aneurysm during the procedure, a buddy wire was loaded prophylactically into the sac through the contralateral limb side. If a type Ia endoleak (ELIa) occurred and persisted despite adjunctive treatment such as balloon moulding or cuff extension, this preloaded wire could be utilized to enable a catheter to reach the space between the stent graft and sac neck to perform coil embolization. In the absence of ELIa, the wire was simply retracted. The primary outcome of this study was freedom from sac expansion and endoleak-related reintervention during the follow-up period; secondary outcomes included technical success and intraoperative and in-hospital postoperative complications. RESULTS: Among the 28 patients with a hostile neck morphology, 11 (39.5%) who presented with ELIa underwent intraprocedural treatment involving sac neck-targeted detachable coil embolization. Seventeen individuals (60.7%) of the total patient population did not undergo coiling. All patients in the coiling group underwent balloon moulding, and 2 patients additionally underwent cuff extension. In the noncoiling group, 14 individuals underwent balloon moulding as a treatment for ELIa, while 3 patients did not exhibit ELIa during the procedure. The coiling group showed longer operating durations (81.27 ± 11.61 vs. 70.71 ± 7.17 min, P < 0.01) and greater contrast utilization than the noncoiling group (177.45 ± 52.41 vs. 108.24 ± 17.49 ml, P < 0.01). In the entire cohort, the technical success rate was 100%, and there were no procedure-related complications. At a mean follow-up of 18.6 ± 5.2 months (range 12-31), there were no cases of sac expansion (19 cases of sac regression, 67.86%; 9 cases of stability, 32.14%) or endoleak-related reintervention. CONCLUSIONS: Selective aneurysmal sac neck-targeted embolization for the treatment of ELIa in AAA patients with an HNA undergoing EVAR is safe and may prevent type Ia endoleak and related sac expansion after EVAR.

A protocol of Chinese expert consensuses for the management of health risk in the general public.

Introduction: Non-communicable diseases (NCDs) represent the leading cause of mortality and disability worldwide. Robust evidence has demonstrated that modifiable lifestyle factors such as unhealthy diet, smoking, alcohol consumption and physical inactivity are the primary causes of NCDs. Although a series of guidelines for the management of NCDs have been published in China, these guidelines mainly focus on clinical practice targeting clinicians rather than the general population, and the evidence for NCD prevention based on modifiable lifestyle factors has been disorganized. Therefore, comprehensive and evidence-based guidance for the risk management of major NCDs for the general Chinese population is urgently needed. To achieve this overarching aim, we plan to develop a series of expert consensuses covering 15 major NCDs on health risk management for the general Chinese population. The objectives of these consensuses are (1) to identify and recommend suitable risk assessment methods for the Chinese population; and (2) to make recommendations for the prevention of major NCDs by integrating the current best evidence and experts' opinions. Methods and analysis: For each expert consensus, we will establish a consensus working group comprising 40-50 members. Consensus questions will be formulated by integrating literature reviews, expert opinions, and an online survey. Systematic reviews will be considered as the primary evidence sources. We will conduct new systematic reviews if there are no eligible systematic reviews, the methodological quality is low, or the existing systematic reviews have been published for more than 3 years. We will evaluate the quality of evidence and make recommendations according to the GRADE approach. The consensuses will be reported according to the Reporting Items for Practice Guidelines in Healthcare (RIGHT).

A machine learning diagnostic model for Pneumocystis jirovecii pneumonia in patients with severe pneumonia.

BACKGROUND: The diagnosis of Pneumocystis jirovecii pneumonia (PCP) in patients presenting with severe pneumonia is challenging and delays in treatment were associated with worse prognosis. This study aimed to develop a rapid, easily available, noninvasive machine learning diagnostic model for PCP among patients with severe pneumonia. METHODS: A retrospective study was performed in West China Hospital among consecutive patients with severe pneumonia who had undergone bronchoalveolar lavage for etiological evaluation between October 2010 and April 2021. Factors associated with PCP were identified and four diagnostic models were established using machine learning algorithms including Logistic Regression, eXtreme Gradient Boosting, Random Forest (RF) and LightGBM. The performance of these models were evaluated by the area under the receiver operating characteristic curve (AUC). RESULTS: Ultimately, 704 patients were enrolled and randomly divided into a training set (n = 564) and a testing set (n = 140). Four factors were ultimately selected to establish the model including neutrophil, globulin, ß-D-glucan and ground glass opacity. The RF model exhibited the greatest diagnostic performance with an AUC of 0.907. The calibration curve and decision curve analysis also demonstrated its accuracy and applicability. CONCLUSIONS: We constructed a PCP diagnostic model in patients with severe pneumonia using four easily available and noninvasive clinical indicators. With satisfying diagnostic performance and good clinical practicability, this model may help clinicians to make early diagnosis of PCP, reduce the delays of treatment and improve the prognosis among these patients.

Pulmonary CT imaging findings in fat embolism syndrome: case series and literature review.

BACKGROUND: Fat embolism syndrome (FES) is a rare life-threatening complication, which commonly affects the lung. Currently, the most widely accepted criteria for the diagnosis of FES are the Gurd and Wilson Criteria established nearly 40 years ago, but without pulmonary images involved. Our study aims to analyse the pulmonary computed tomography (CT) findings seen in FES. CASE PRESENTATION: This report enrolled four cases of FES with lung involvement. The mainly symptoms and signs included dyspnea, disturbance of consciousness, anemia, thrombocytopenia and, most notably, ground-glass opacities, septal thickening, ill-defined centrilobular nodules, and patchy consolidation were demonstrated on bilateral lungs. Combining the clinical manifestations and laboratory tests, the diagnosis of FES was confirmed. With the treatment of steroids, anti-coagulation and supportive treatment, the four patients' symptoms were relieved, abnormalities in chest CT were absorbed significantly and the patients were finally discharged. CONCLUSIONS: There are several common manifestations of FES in pulmonary CT images, and the lung parenchymal features give more information for the diagnosis of FES than the pulmonary vessel findings. Given the absence of a gold standard diagnostic test for FES, further investigation to explore new diagnostic criteria of FES involving pulmonary radiological features is needed in the future.

Successful Application of Argatroban During VV-ECMO in a Pregnant Patient Complicated With ARDS due to Severe Tuberculosis: A Case Report and Literature Review.

Severe tuberculosis during pregnancy may progress to acute respiratory distress syndrome (ARDS), and venovenous (VV) extracorporeal membrane oxygenation (ECMO) should be considered if conventional lung-protective mechanical ventilation fails. However, thrombocytopenia often occurs with ECMO, and there are limited reports of alternative anticoagulant therapies for pregnant patients with thrombocytopenia during ECMO. This report describes the first case of a pregnant patient who received argatroban during ECMO and recovered. Furthermore, we summarized the existing literature on VV-ECMO and argatroban in pregnant patients. A 31-year-old woman at 17 weeks of gestation was transferred to our hospital with ARDS secondary to severe tuberculosis. We initiated VV-ECMO after implementing a protective ventilation strategy and other conventional therapies. Initially, we selected unfractionated heparin anticoagulant therapy. However, on ECMO day 3, the patient's platelet count and antithrombin III (AT-III) level declined to 27 × 103 cells/µL and 26.9%, respectively. Thus, we started the patient on a 0.06 µg/kg/min argatroban infusion. The argatroban infusion maintenance dose ranged between 0.9 and 1.2 µg/kg/min. The actual activated partial thromboplastin clotting time and activated clotting time ranged from 43 to 58 s and 220-260 s, respectively, without clinically significant bleeding and thrombosis. On day 27, the patient was weaned off VV-ECMO and eventually discharged. VV-ECMO may benefit pregnant women with refractory ARDS, and argatroban may be an alternative anticoagulant for pregnant patients with thrombocytopenia and AT-III deficiency during ECMO.

Validation of Risk Assessment Models Predicting Venous Thromboembolism in Inpatients with Acute Exacerbation Of Chronic Obstructive Pulmonary Disease: A Multicenter Cohort Study in China.

BACKGROUND: Inpatients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are at increased risk for venous thromboembolism (VTE); however, the prophylaxis for VTE is largely underused in China. Identifying high-risk patients requiring thromboprophylaxis is critical to reduce the mortality and morbidity associated with VTE. This study aimed to evaluate and compare the validities of the Padua Prediction Score and Caprini risk assessment model (RAM) in predicting the risk of VTE in inpatients with AECOPD in China. METHODS: The inpatients with AECOPD were prospectively enrolled from seven medical centers of China between September 2017 and January 2020. Caprini and Padua scores were calculated on admission, and the incidence of 3-month VTE was investigated. RESULTS: Among the 3,277 eligible patients with AECOPD, 128 patients (3.9%) developed VTE within 3 months after admission. The distribution of the study population by the Caprini risk level was as follows: high, 53.6%; moderate, 43.0%; and low, 3.5%. The incidence of VTE increased by risk level as high, 6.1%; moderate, 1.5%; and low, 0%. According to the Padua RAM, only 10.9% of the study population was classified as high risk and 89.1% as low risk, with the corresponding incidence of VTE of 7.9 and 3.4%, respectively. The Caprini RAM had higher area under curve compared with the Padua RAM (0.713 ± 0.021 vs. 0.644 ± 0.023, p = 0.029). CONCLUSION: The Caprini RAM was superior to the Padua RAM in predicting the risk of VTE in inpatients with AECOPD and might better guide thromboprophylaxis in these patients.

Crazy-paving patterns as rare radiological manifestations of pulmonary cryptococcosis: a case report.

BACKGROUND: Crazy-paving patterns are rarely reported as radiological manifestations of pulmonary cryptococcosis. CASE PRESENTATION: Herein, we presented a very rare case of a crazy-paving pattern as a radiological manifestation of pulmonary cryptococcosis in a patient with primary ciliary dyskinesia. The diagnosis of pulmonary cryptococcosis and primary ciliary dyskinesia was ultimately confirmed by bronchoscopic biopsy, fungus culture, whole exome sequencing of blood, etc. The patient received flucytosine (PO, 5 g per day) and amphotericin B (IV, 70 mg per day) during hospitalization and sequential therapy with voriconazole (PO, 200 mg twice a day) after discharge. He recovered during follow-up. CONCLUSIONS: We concluded that pulmonary cryptococcosis should be considered a possible cause of crazy-paving patterns in chest CT scans.

Comparison of Different Clinical Prognostic Scores in Patients with Pulmonary Embolism and Active Cancer.

OBJECTIVE: This article aimed to validate and compare the prognostic performance of generic scores (Pulmonary Embolism Severity Index [PESI] and Hestia) and cancer-specific pulmonary embolism (PE)/venous thromboembolism (VTE) scales (Registro Informatizado de la Enfermedad TromboEmbólica [RIETE], POMPE-C, and modified Ottawa) in PE patients with active cancer. METHODS: A retrospective study was conducted among 460 patients with PE and active cancer. The primary outcome was 30-day overall mortality. Secondary outcomes were 30-day PE-related death and overall adverse outcomes. The prognostic accuracy of clinical scores was determined using receiver operating characteristic (ROC) curve analysis. RESULTS: Within 30 days, 18.0% of patients died, 2.0% suffered major bleeding, and 0.2% presented recurrence of VTE. All scales showed a high area under the ROC curve (AUC) for predicting 30-day overall mortality except modified Ottawa (0.74 [0.70-0.78] for PESI, Hestia, and RIETE; 0.78 (0.74-0.81) for POMPE-C; 0.64 (0.59-0.68) for modified Ottawa]. PESI divided the least patients (9.1%) into low risk, followed by modified Ottawa (17.0%). Hestia stratified the most patients (65.4%) as low risk. But overall mortality of low-risk patients based on these three scales is high (>5%). RIETE and POMPE-C both classified 30.9% of patients as low risk, and low-risk patients stratified by these two scales presented a low overall mortality (1.4 and 3.5%). Similar predictive performance was found for 30-day PE-related death and overall adverse outcomes in these scores. CONCLUSION: Cancer-specific PE prognostic scores (RIETE and POMPE-C) performed better than generic scales (PESI and Hestia) and a cancer-specific VTE prognostic scale (modified Ottawa) in identifying low-risk PE patients with active cancer who may be suitable for outpatient treatment.

Comparison between the Khorana prediction score and Caprini risk assessment models for assessing the risk of venous thromboembolism in hospitalized patients with cancer: a retrospective case control study.

OBJECTIVES: This study aimed to evaluate the optimal risk assessment model (RAM) to stratify the risk of venous thromboembolism (VTE) in hospitalized patients with cancer. We examined and compared the VTE predictive ability of the Khorana score (KS) and the Caprini RAM in hospitalized cancer patients. METHODS: We performed a retrospective case-control study among hospitalized cancer patients admitted to a comprehensive hospital in China from January 2015 to December 2016. A total of 221 cases were confirmed to have VTE during hospitalization and 221 controls were selected randomly. The Caprini RAM and KS were implemented and the individual scores of each risk factor were summed to generate a cumulative risk score. Meanwhile, the sensitivity, specificity, areas under curve of the receiver operating characteristic curve and calibration of these 2 models were analysed. RESULTS: Significant differences were observed in risk factors between VTE and non-VTE hospitalized cancer patients and the VTE risk increased significantly with an increase in the cumulative KS or Caprini RAM score. A classification of 'high risk' according to KS and Caprini RAM was associated with 2.272-fold and 3.825-fold increases in VTE risk, respectively. However, the Caprini RAM could identify 82.4% of the VTE cases that required preventive anticoagulant therapy according to American College of Chest Physicians guidelines, whereas the KS could only identify 35.3% of the VTE cases. In addition, the areas under curve of Caprini RAM were significantly higher than those of the KS (0.705 ± 0.024 vs 0.581 ± 0.025, P < 0.001), with a best cut-off value of 5 score, which happened to be the cut-off value for high risk of VTE in Caprini RAM. Both Caprini RAM and KS showed an excellent calibration curve (0.612 vs 0.141, P > 0.05), but the risk of VTE events predicted by Caprini seemed closer to the observed risk of VTE events. CONCLUSIONS: The Caprini RAM was found to be more effective than the KS in identifying hospitalized patients with cancer at risk of VTE.

Immediate and short-term effects of transcatheter device closure of large atrial septal defect in senior people.

OBJECTIVES: We sought to evaluate the safety and efficacy in improving cardiac function and functional capacity with device closure of large atrial septal defects (ASD) in senior adults. BACKGROUND: Atrial septal defect accounts for about 10% of all congenital heart disease. It still remains unclear whether large ASD closure in senior people should be performed or not. Hence we aim to prospectively assess the safety and clinical status of senior patients after transcatheter closure in large ASD. PATIENTS AND INTERVENTIONS: This was a prospective study of all patients aged over 50 years who underwent device closure of a secundum large ASD between January 2013 and January 2018. Investigations including brain natriuretic peptide level, electrocardiography, chest X-ray, transthoracic echocardiogram, transesophageal echocardiogram, and 6-minute walk test were performed before and at 2 days and 4 weeks and 6 months after the procedure. RESULTS: Twenty patients (median age 68 years, 10 women) had transcatheter device closure of large ASD successfully. Median ASD size was 32 mm (range 30-39 mm). Median pulmonary artery pressure was 58 mm Hg (range 47-67 mm Hg). At 6 months, there was a significant change in right atrium size (P < .001) and right ventricle size (P < .01) and left ventricle size (P < .001) and also pulmonary artery pressure (P < .0001), New York Heart Association functional class improved (P = .03) in 19 patients and also significant improvement in 6-minute walk test distance (P < .001). There were no major complications. CONCLUSIONS: Our data showed that large ASD closure at senior people results in satisfactory cardiac remodeling and cardiac function improvement.

Smad3 promotes cancer progression by inhibiting E4BP4-mediated NK cell development.

TGF-ß is known to influence tumour progression. Here we report an additional role of Smad3 in the tumour microenvironment regulating cancer progression. Deletion or inhibition of Smad3 in the tumour microenvironment suppresses tumour growth, invasion and metastasis in two syngeneic mouse tumour models. Smad3-/- bone marrow gives rise to an expanded NK cell population with enhanced tumour-suppressive activities in vivo, and promotes differentiation of NK cells ex vivo. We identify E4BP4/NFIL3 as a direct Smad3 target gene critical for NK cell differentiation. Smad3 suppresses transcription of IFN-γ via E4BP4 in a T-bet independent manner. Therefore disruption of Smad3 enhances both the E4BP4-mediated NK cell differentiation and anti-cancer effector functions in vivo and in vitro. Furthermore, systemic treatment with a Smad3 inhibitor SIS3 effectively suppresses cancer progression. In summary, suppression of NK cell-mediated immunosurveillance via the Smad3-E4BP4 axis contributes to cancer progression. We propose targeting Smad3-dependent tumour microenvironment may represent an effective anti-cancer strategy.

Endothelial Cell Mediated Promotion of Ciliated Cell Differentiation of Human Airway Basal Cells via Insulin and Insulin-Like Growth Factor 1 Receptor Mediated Signaling.

Human airway basal cells (BC) function as stem/progenitor cells of the human airway epithelium, capable of differentiating into ciliated and secretory cells during turnover and repair. The positioning of BC along the basement membrane allows for potential paracrine signaling from non-epithelial cells in the mesenchyme to regulate BC function. Based on the knowledge that interaction between the airway epithelium and mesenchyme is critical for proper maintenance of both tissues, and that endothelial cells (EC) can regulate multiple functions of BC, the present study was designed to help understand the role of BC and EC cross-talk in regulating BC stem/progenitor function. Using an in vitro co-culture system that mimics the in vivo physical separation of these cell types, we assessed the impact of primary lung microvascular EC on differentiation of primary BC into a mucociliated epithelium. The data demonstrate that co-culture of BC and lung microvasculature EC results in increased ciliated cell differentiation of BC via activation of insulin (INS) and insulin-like growth factor 1 (IGF1) receptor (INSR and IGF1R) mediated signaling in BC. Consistent with this data, siRNA mediated knockdown of INSR and IGF1R in BC suppressed ciliated cell differentiation. Together these findings identify an important signaling pathway required for differentiation of BC into a ciliated cells and demonstrate the importance of BC-EC cross-talk in regulating normal airway epithelial structure.

The measurement of lung volumes using body plethysmography and helium dilution methods in COPD patients: a correlation and diagnosis analysis.

Chronic obstructive pulmonary disease (COPD) is a chronic airway disease characterized by persistent airflow limitation. Moreover, lung hyperinflation evaluated by lung volumes is also the key pathophysiologic process during COPD progression. Nevertheless, there is still no preferred method to evaluate lung volumes. For this study, we recruited 170 patients with stable COPD to assess lung volumes stratified by airflow limitation severity. Lung volumes including residual volume (RV) and total lung capacity (TLC) were determined by both body plethysmography and helium dilution methods. The discrepancies between these two methods were recorded as ΔRV%pred, ΔTLC%pred, and ΔRV/TLC. We found that ΔRV%pred, ΔTLC%pred, and ΔRV/TLC increased significantly with the severity of COPD. The differences of lung capacity between these two methods were negatively correlated with FEV1%pred, and diffusing capacity for carbon monoxide (DLCO%pred). Moreover, the receiver operating characteristic (ROC) for ΔTLC%pred to distinguish severe COPD from non-severe COPD had an area under curve (AUC) of 0.886. The differences of lung volume parameters measured by body plethysmography and helium dilution methods were associated with airflow limitation and can effectively differentiate COPD severity, which may be a supportive method to assess the lung function of stable COPD patients.

TGF-ß/Smad3 signalling regulates the transition of bone marrow-derived macrophages into myofibroblasts during tissue fibrosis.

Myofibroblasts are a main cell-type of collagen-producing cells during tissue fibrosis, but their origins remains controversial. While bone marrow-derived myofibroblasts in renal fibrosis has been reported, the cell origin and mechanisms regulating their transition into myofibroblasts remain undefined. In the present study, cell lineage tracing studies by adoptive transfer of GFP+ or dye-labelled macrophages identified that monocyte/macrophages from bone marrow can give rise to myofibroblasts via the process of macrophage-myofibroblast transition (MMT) in a mouse model of unilateral ureteric obstruction. The MMT cells were a major source of collagen-producing fibroblasts in the fibrosing kidney, accounting for more than 60% of α-SMA+ myofibroblasts. The MMT process occurred predominantly within M2-type macrophages and was regulated by TGF-ß/Smad3 signalling as deletion of Smad3 in the bone marrow compartment of GFP+ chimeric mice prevented the M2 macrophage transition into the MMT cells and progressive renal fibrosis. In vitro studies in Smad3 null bone marrow macrophages also showed that Smad3 was required for TGF-ß1-induced MMT and collagen production. In conclusion, we have demonstrated that bone marrow-derived fibroblasts originate from the monocyte/macrophage population via a process of MMT. This process contributes to progressive renal tissue fibrosis and is regulated by TGF-ß/Smad3 signalling.