Identifying potential drug targets for idiopathic pulmonary fibrosis: a mendelian randomization study based on the druggable genes.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic interstitial lung disease characterized by progressive dyspnea and decreased lung function, yet its exact etiology remains unclear. It is of great significance to discover new drug targets for IPF. METHODS: We obtained the cis-expression quantitative trait locus (cis-eQTL) of druggable genes from eQTLGen Consortium as exposure and the genome wide association study (GWAS) of IPF from the International IPF Genetics Consortium as outcomes to simulate the effects of drugs on IPF by employing mendelian randomization analysis. Then colocalization analysis was performed to calculate the probability of both cis-eQTL of druggable genes and IPF sharing a causal variant. For further validation, we conducted protein quantitative trait locus (pQTL) analysis to reaffirm our findings. RESULTS: The expression of 45 druggable genes was significantly associated with IPF susceptibility at FDR < 0.05. The expression of 23 and 15 druggable genes was significantly associated with decreased forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLco) in IPF patients, respectively. IPF susceptibility and two significant genes (IL-7 and ABCB2) were likely to share a causal variant. The results of the pQTL analysis demonstrated that high levels of IL-7 in plasma are associated with a reduced risk of IPF (OR = 0.67, 95%CI: 0.47-0.97). CONCLUSION: IL-7 stands out as the most promising potential drug target to mitigate the risk of IPF. Our study not only sheds light on potential drug targets but also provides a direction for future drug development in IPF.

Carrier rate of thalassemia among 25,910 high school students in Shaoguan area, China.

OBJECTIVES: As one of the most common hereditary diseases, thalassemia affects a large number of people in China. The aim of this study was to investigate the feasibility of a method based on next-generation sequencing (NGS) for screening of thalassemia carriers among high school students in the Shaoguan area. MATERIALS AND METHODS: The NGS-based method was performed using 25,910 high school students recruited from 38 schools. The screening yield was systematically analyzed. Before screening, a lecture on how the disease is inherited, the symptoms of thalassemia, and how to prevent it was given to 28,780 students. RESULTS: Implying successful delivery of information on the disease, 90.03% (25,910 of 28,780) of the students agreed to join this program for thalassemia screening. A thalassemia carrier rate of 15.99% (4144 of 25,910) was found. Also, 69 rare genotypes (28 of α-thalassemia and 41 of ß-thalassemia) and 9 novel variants were identified. CONCLUSIONS: This NGS-based method provided a feasible platform for high school population thalassemia screening. Combined with a clinical follow-up strategy, it could help eventually to prevent the births of affected children.

Differential efficacy of segmentectomy and wedge resection in sublobar resection compared to lobectomy for solid-dominant stage IA lung cancer: a systematic review and meta-analysis.

BACKGROUND: Currently, the impact of sublobar resection versus lobectomy on the prognosis of solid-dominant stage IA lung cancer is contradictory in different studies, which requires further exploration. METHODS: The authors analyzed 26 studies, including one randomized controlled trial and retrospective cohort studies. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models based on heterogeneity levels. RESULTS: The analysis included 12 667 patients, with 3488 undergoing sublobar resections and 9179 receiving lobectomies. The overall analysis revealed no statistically significant difference in overall survival (OS) (HR=1.28, 95% CI: 0.98-1.69) between sublobar resection and lobectomy, but lobectomy was associated with better recurrence-free survival (RFS) (HR=1.39, 95% CI: 1.10-1.75). Subgroup analyses revealed that, for tumors with a diameter ≤2 cm, sublobar resection versus lobectomy showed no significant difference in OS but sublobar resection had lower RFS. For 2-3 cm tumors, both OS and RFS were significantly lower in the sublobar resection group. When consolidation-to-tumor ratio (CTR) ranged from 0.5 to <1, OS did not differ significantly, but RFS was significantly lower in sublobar resection. Lung cancers with CTR=1 showed significantly lower OS and RFS in the sublobar resection group. Segmentectomy provided similar OS and RFS compared to lobectomy, while wedge resection had a detrimental effect on patient prognosis. However, wedge resection may have provided comparable outcomes for patients aged 75 years or older. CONCLUSION: Our findings suggest that segmentectomy and lobectomy yield similar oncological outcomes. However, compared to lobectomy, wedge resection is associated with a poorer prognosis. Nevertheless, for elderly patients, wedge resection is also a reasonable surgical option.

Video-assisted thoracic surgery drainage is feasible and safe for acute necrotizing mediastinitis: a retrospective cohort study.

Background: Acute necrotizing mediastinitis (ANM) is a severe infection of the mediastinal loose connective tissue. Traditionally, it has been treated with thoracotomy, but video-assisted thoracic surgery (VATS) is been increasingly used in patients with this condition. This study aimed to compare the outcomes of VATS and open thoracotomy in treating ANM. Methods: The medical records of patients with ANM who underwent surgery between March 2012 and April 2021 were retrieved. A retrospective screening was conducted based on clinical characteristics, bacterial pathogens, surgical approach, and outcomes. The patients were divided into a VATS group and an open thoracotomy (Open) group. The patient characteristics and surgical outcomes of the two groups were summarized and compared. Results: A total of 64 cases were enrolled in this study, including 48 in the VATS group (75%) and 16 in the Open group (25%). The most common site of infection was the neck (n=26, 40.6%). Streptococcus constellatus and Acinetobacter baumannii (A. baumannii) were the most frequently found pathogens in secretion culture. In sputum culture, the most common pathogens were Klebsiella pneumonia and A. baumannii. Postoperative outcomes, including blood transfusion (33.3% vs. 43.8%; P=0.45), duration of postoperative drainage {14 [1-47] vs. 17 [4-54] days; P=0.15}, length of antibiotic medication {14.5 [1-54] vs. 18 [4-54] days; P=0.29}, admission to intensive care unit (ICU) (87.5% vs. 75.0%; P=0.43), length of ICU stay {5 [1-58] vs. 8.5 [1-37] days; P=0.20}, postoperative hospital stay {17 [2-61] vs. 21 [5-56] days; P=0.22}, reoperation rate (12.5% vs. 6.25%; P=0.82), and mortality rate (14.6% vs. 12.5%; P>0.99) were comparable between the two groups. Conclusions: ANM treated by both the VATS and open approach had comparable outcomes. Therefore, VATS is a viable option for patients with ANM.

Adjuvant therapy for orbital non-rhabdomyosarcoma soft tissue sarcoma: comparison of long-term outcome between radiotherapy and chemotherapy.

AIM: To illustrate clinicopathological features of orbital non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), and to compare the treatment outcome between postoperative radiotherapy (RT) and chemotherapy in a retrospective analysis nearly 20y. METHODS: A retrospective cohort study of 56 patients with orbital NRSTS were reviewed, 34 of whom received postoperative RT, and 22 received postoperative chemotherapy. The clinicopathological features, local recurrence, metastases, and survival data were recorded. Survival analysis was performed using the Kaplan-Meier method. RESULTS: During follow-up (111.8mo, ranged 8-233mo) for 56 patients, 19 patients of them developed local recurrence, and 7 patients developed distant metastases. Fifteen patients died during follow-up period. Overall survival rates considering the whole study group was 78.57% at 5y, and 72.16% at 10y after the initial diagnosis. Compared with chemotherapy, RT was associated with lower risk of local recurrence [hazard ratio for RT vs chemotherapy, 0.263, 95% confidence interval (CI), 0.095-0.728, P=0.0015]; with lower risk of distant metastasis (hazard ratio for RT vs chemotherapy, 0.073, 95%CI, 0.015-0.364, P=0.0014); and with lower risk of death from disease (hazard ratio for RT vs chemotherapy, 0.066, 95%CI, 0.022-0.200, P<0.0001). The 5-year survival rate in RT group was 97.06% compared to 50% in chemotherapy group. CONCLUSION: In patients with orbital NRSTS, postoperative RT provides better control of local recurrence, distant metastasis, and death from disease than chemotherapy. RT is the more preferrable adjuvant therapy compared to chemotherapy possibly.

Optical coherence tomography enhanced depth imaging of chorioretinal folds in patients with orbital tumors.

AIM: To characterize spectral-domain optical coherence tomography (SD-OCT) features of chorioretinal folds in orbital mass imaged using enhanced depth imaging (EDI). METHODS: Prospective observational case-control study was conducted in 20 eyes of 20 patients, the uninvolved eye served as a control. All the patients underwent clinical fundus photography, computed tomography, EDI SD-OCT imaging before and after surgery. Two patients with cavernous hemangiomas underwent intratumoral injection of bleomycin A5; the remaining patients underwent tumor excision. Patients were followed 1 to 14mo following surgery (average follow up, 5.8mo). RESULTS: Visual acuity prior to surgery ranged from 20/20 to 20/200. Following surgery, 5 patients' visual acuity remained unchanged while the remaining 15 patients had a mean letter improvement of 10 (range 4 to 26 letters). Photoreceptor inner/outer segment defects were found in 10 of 15 patients prior to surgery. Following surgical excision, photoreceptor inner/outer segment defects fully resolved in 8 of these 10 patients. CONCLUSION: Persistence of photoreceptor inner/outer segment defects caused by compression of the globe by an orbital mass can be associated with reduced visual prognosis. Our findings suggest that photoreceptor inner/outer segment defects on EDI SD-OCT could be an indicator for immediate surgical excision of an orbital mass causing choroidal compression.

Clinical impacts of genome-wide noninvasive prenatal testing for rare autosomal trisomy.

BACKGROUND: Genome-wide noninvasive prenatal testing identifies several rare autosomal trisomies in the general obstetrical population, but its use is questioned by its low positive predictive value. Furthermore, the origin of rare autosomal trisomies and the clinical effect of reporting them has not been sufficiently investigated. In addition, professional societies express their need for data assessing the clinical use of genome-wide noninvasive prenatal testing for rare autosomal trisomies for years. OBJECTIVE: This study aimed to investigate the origin of rare autosomal trisomies and the clinical effect of disclosing rare autosomal trisomies in clinical settings. STUDY DESIGN: Women who received noninvasive prenatal testing between March 2021 and March 2022 were prospectively enrolled. Clinical follow-up and cytogenetic and molecular investigations were performed. Posthoc analysis was performed to investigate the association between placental mosaicism and clinical outcomes. RESULTS: Overall, 154 rare autosomal trisomies were identified in 89,242 pregnancies (0.17%) through noninvasive prenatal testing. In the 120 cases in which cytogenetic and molecular investigations were carried out, the rare autosomal trisomies were found to originate from true fetal mosaicism (n=5), uniparental disomy (n=5), maternal mosaic trisomy (n=3), maternal malignancy (n=1), and confined placental mosaicism (n=106). Clinical follow-up showed that 40% of all rare autosomal trisomy cases had adverse perinatal outcomes. In women with false-positive noninvasive prenatal testing results originating from confined placental mosaicism, the frequency of adverse perinatal outcomes was 26%. More importantly, the placental mosaicism ratio revealed by noninvasive prenatal testing was significantly higher in women who experienced adverse perinatal outcomes than those who did not (0.688 vs 0.332; P<.001). CONCLUSION: Women with noninvasive prenatal testing results indicative of rare autosomal trisomies are at risk of adverse perinatal outcomes, and that risk can be stratified using chromosomes and the mosaicism ratio revealed by noninvasive prenatal testing. Our data are valuable for obstetrical caregivers advising a patient with a noninvasive prenatal testing result indicative of a rare autosomal trisomy and a false-positive diagnosis and for managing risks during pregnancy.

Prognostic role of the platelet to lymphocyte ratio (PLR) in the clinical outcomes of patients with advanced lung cancer receiving immunotherapy: A systematic review and meta-analysis.

Background: It remains controversial whether the platelet to lymphocyte ratio (PLR) serves as a potential indicator for the efficacy of immunotherapy in advanced lung cancer. This meta-analysis aimed to address this concern. Methods: Up to March 2022, we searched PubMed, Embase, Web of Science and the Cochrane Library to retrieve potentially eligible articles. Combined hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated to assess the relationship between PLR and progression-free survival (PFS) as well as overall survival (OS), while the combined odds ratios (ORs) and 95% CIs were estimated to evaluate the relationship between PLR and the objective response rate (ORR) as well as the disease control rate (DCR). Subgroup analyses were further performed to detect the source of heterogeneity and potential predictive value of PLR in different groups in terms of OS and PFS. Results: A total of 21 included studies involving 2312 patients with advanced lung cancer receiving immunotherapy were included. The combined results suggested that elevated PLR was associated with poorer OS (HR=2.24; 95% CI: 1.87-2.68; I² =44%; P=0.01) and PFS (HR=1.66; 95% CI: 1.36-2.04; I² =64%; P<0.01). Furthermore, elevated PLR showed a lower ORR (OR= 0.61; 95% CI: 0.43-0.87, I²=20%; P=0.29) and DCR (OR= 0.44; 95% CI: 0.27-0.72, I²=61%; P=0.02). In subgroup analyses, pretreatment PLR was significantly associated with adverse OS and PFS. The same results were observed in different PLRs in terms of cutoff value (>200 vs. ≤200). Furthermore, high PLR was significantly associated with poor OS and PFS in advanced non-small cell lung cancer (NSCLC); however, PLR was not associated with OS and PFS in advanced small cell lung cancer (SCLC). In addition, PLR predicted poor OS irrespective of regions and types of immune checkpoint inhibitors (ICIs). Conclusion: On the whole, patients with low PLR had better OS and PFS, as well as higher ORR and DCR when receiving immunotherapy in advanced lung cancer especially for advanced NSCLC. And further investigations are warranted to confirm the prognostic value of PLR in advanced SCLC. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022315976.

Surgery and chemotherapy cannot improve the survival of patients with early-stage mucosa-associated lymphoid tissue derived primary pulmonary lymphoma.

Background: To date, there is no treatment consensus on mucosa-associated lymphoid tissue (MALT) derived primary pulmonary lymphoma (PPL). Methods: We identified patients with early-stage MALT-type PPL from the National Cancer Institute's Surveillance, Epidemiology, and End Results program database. The patients were divided into four groups according to treatment modalities: None of surgery or chemotherapy (None) group, Surgery alone group, Chemotherapy alone (Chemo alone) group, and Surgery plus chemotherapy (Surgery + chemo) group. Overall survival (OS) and cancer-specific survival (CSS) were study endpoints. We performed Cox regression analyses, propensity score-matched analyses (PSM) and Kaplan-Meier (KM) survival curves to compare the survival among different groups. Results: A total of 953 patients were included in our analysis with 302, 403, 175, and 73 cases in the None, Surgery alone, Chemo alone, and Surgery + chemo groups, respectively. In this cohort, the estimated 3-year, 5-year and 10-year OS rates were 86.95%, 78.91%, and 55.89%, respectively. Meanwhile, the estimated 3-year, 5-year and 10-year CSS rates were 96.71%, 93.73%, and 86.84%, respectively. Multivariate Cox regression analyses demonstrated that increasing age, tumors located in the lower lobe, and stage II were significant predictors of poorer OS while increasing age and tumors located in the bilateral lungs were associated with lower CSS. After PSM analyses, the KM survival curves showed no significant differences in OS or CSS among the four groups. Conclusion: Early-stage MALT-type PPL is indolent in nature. Neither surgery, chemotherapy nor a combination of surgery and chemotherapy can improve OS and CSS, suggesting that "watch and wait" may be a reasonable alternative.

Adjuvant chemotherapy may improve long-term outcomes in stage IB non-small cell lung cancer patients with previous malignancies: A propensity score-matched analysis.

Background: Routine administration of adjuvant chemotherapy for stage IB non-small cell lung cancer (NSCLC) remains controversial. To our knowledge, no available studies have assessed the outcomes of chemotherapy in patients with stage IB NSCLC who had prior malignancies. Methods: Patients with pathological stage IB NSCLC with previous malignancies who underwent surgery between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were categorized into chemotherapy and observation group based on whether they received adjuvant chemotherapy. Propensity score matching was performed to reduce confounding bias, and Kaplan-Meier curves and log-rank tests were used to compare overall survival (OS) and cancer-specific survival (CSS) between the two groups. Subgroup analyses of the matched cohorts were then conducted to evaluate the relationship between clinical features and chemotherapy. Results: A total of 894 eligible patients were identified; 90 (10.1%) patients received postoperative chemotherapy. Patients who received adjuvant chemotherapy obtained obvious OS benefits compared with those who received observation alone (HR = 0.68, 95% CI: 0.48-0.97, P = 0.031). In addition, the 5-year OS rate and median OS time in the chemotherapy group were higher and longer, respectively. Although chemotherapy offered no obvious benefits for CSS (HR = 0.80, 95% CI: 0.57-1.14, P = 0.35), patients who received chemotherapy showed a better 5-year CSS rate. On subgroup analyses, a chemotherapy advantage was observed in advanced age (≥65 years, HR = 0.62, 95% CI: 0.38-0.99, P = 0.045). The same chemotherapy advantages were observed in patients diagnosed with higher histological grades (poorly differentiated to undifferentiated) (HR = 0.56, 95% CI: 0.33-0.96, P = 0.033) and tumor sizes >3.1-4 cm (HR = 0.57, 95% CI: 0.37-0.87, P = 0.010). Interestingly, NSCLC patients with previous malignancies originating from the kidney and bladder (HR = 0.34, 95% CI: 0.12-0.99, P = 0.049) showed a chemotherapy advantage. The same chemotherapy advantages were observed in patients diagnosed with NSCLC within 3 to 5 years after prior cancers (HR = 0.39, 95% CI: 0.16-0.98, P = 0.044) and with localized SEER stage of prior cancers (HR = 0.49, 95% CI: 0.29-0.86, P = 0.012). Conclusion: These findings indicate that adjuvant chemotherapy may improve long-term outcomes for stage IB NSCLC patients with previous malignancies. It is recommended that physicians consider the clinical features of previous cancers when making adjuvant chemotherapy decisions for these patients.

Risk factors and outcomes of bronchopleural fistula after bronchoplasty in patients with non-small cell lung cancer: a retrospective multivariate analysis.

Background: Bronchopleural fistula (BPF) is a rare but severe complication following bronchoplasty. Identification of the risk factors for the development of BPF after bronchoplasty may contribute to better perioperative management, thereby further improving the prognosis of these patients. However, few studies have focused on the risk factors for BPF after bronchoplasty. This study aimed to explore the risk factors and outcomes for BPF after bronchoplasty in patients with non-small cell lung cancer (NSCLC). Methods: The data of NSCLC patients who underwent bronchoplasty between September 2005 and August 2020 in our institution were retrospectively reviewed. Detailed information on demographic characteristics, preoperative assessment, perioperative outcomes were collected from Western China Lung Cancer Database. The diagnosis of BPF was confirmed by bronchoscopy. Risk factors for BPF were assessed by univariate and multivariate logistic regression analysis. Results: A total of 503 patients were included in this study, including 132 (26.2%) cases of broncho-vascular plasty, 340 (67.6%) cases of bronchial sleeve lobectomy, and 31 (6.2%) cases of bronchial wedge plasty. Among these patients, 16 (3.2%) developed postoperative BPF. Six patients with BPF died during hospital-stay, including two cases of severe hemoptysis, and four cases of pyothorax and respiratory failure caused by BPF. One of the other ten patients underwent reoperation. After univariate and multivariate logistic regression analysis, preoperative Charlson Comorbidity Index (CCI) ≥2 [odds ratio (OR) =5.120, 95% confidence interval (CI): 1.193-21.985, P=0.028], right middle and/or lower lobectomy (OR =4.840, 95% CI: 1.133-20.686, P=0.033), and residual tumor in the bronchial margin (OR =4.160, 95% CI: 1.106-15.644, P=0.035) were identified as independent risk factors for postoperative BPF. Conclusions: Although complication rate of BPF after bronchoplasty is low, the mortality of BPF is high. Patients with higher CCI, those who undergo right middle and/or lower lobectomy, and those with residual tumor in the bronchial margin are at increased risk of BPF. This study highlights the importance of preoperative evaluation and good intraoperative management to prevent this catastrophic complication.

Insights Into Ferroptosis: Targeting Glycolysis to Treat Graves' Orbitopathy.

CONTEXT: Oxidative stress plays an indispensable role in pathogenesis of Graves' orbitopathy (GO). Ferroptosis is a newly discovered form of cell death resulting from lipid peroxidation. Little is known about the role of ferroptosis in GO. OBJECTIVE: We aimed to identify the divergent role of ferroptosis in the GO and control orbital fibroblasts (OFs). METHODS: Orbital fat/connective tissues and serum immunoglobulins (Igs) were collected from GO and control subjects. Cell viability and lipid peroxidation were measured to evaluate ferroptosis sensitivity. Pyruvate dehydrogenase kinase 2 (PDK2) level and oxygen consumption rate were quantified to assess glycolysis status. RESULTS: Primary OFs were cultured from orbital tissues. Ferroptosis was induced by cystine deprivation and/or erastin treatment. The GO OFs possessed stronger resistance to ferroptosis than the control OFs. Selenium, a potential ferroptosis inhibitor, protected the control OFs from ferroptosis. Both transcriptomic and proteomic analyses indicated glycolytic shift in the GO OFs. Metabolic profiling, PDK2 quantification, and oxygen consumption assay confirmed enhanced glycolysis in the GO OFs. Inhibition of glycolysis by PDK2 knockdown and dichloroacetic acid (DCA) promoted ferroptosis sensitivity in the GO OFs. The ferroptosis-sensitizing effects of DCA were also observed when the GO OFs were treated with GO-Igs. IGF1R overexpression in the GO OFs contributed to glycolysis shift. IGF1R inhibitory antibodies facilitated ferroptosis induction in the GO OFs, but the effects were less remarkable under GO-Igs treatment. CONCLUSION: These study findings establish that glycolysis facilitates ferroptosis resistance in the GO OFs, providing insights into the therapeutic role of glycolysis for GO treatment.

Stretch on the L5 nerve root in high-grade spondylolisthesis reduction.

OBJECTIVE: L5 nerve root (L5-NR) injury after surgery for high-grade spondylolisthesis (HGS) was considered a nerve stretch associated with reduction. Currently, however, no study has directly measured the stretch on the L5-NR during HGS reduction procedures. METHODS: CT data of 4 patients with mild lumbar degeneration (control group [CG]) and 4 patients with HGS (spondylolisthesis group [SG]) were used for 3D printing to develop L5 vertebrae and sacrum models. These models were mounted on a self-designed reduction apparatus, which performed vertical translation (disc heights of 0, 5, and 10 mm), anterior-posterior translation (reduction, 0%-100%), and slip-angle correction (0° to -30°). The L5-NR was simulated by using a rabbit sciatic nerve. The cephalic side of the nerve was fixed at the upper base of the L5 pedicle, while the caudal side was connected to a high-precision sensor and an indicator to measure the tension (stretch) on the nerve during the reduction procedures in real time. RESULTS: The SG had shorter L5-NRs than the CG. At a 0-mm disc height, the peak tension on the L5-NR changed from 0 N (reduction 0%) to 1.81 ± 0.54 N (reduction 100%) in the SG and to 1.78 ± 0.71 N in the CG. At a 10-mm disc height, the tension changed from 1.50 ± 0.67 N to 4.97 ± 1.04 N in the SG and from 0.92 ± 0.45 N to 3.26 ± 0.88 N in the CG. In both the CG and SG, at the same disc height, all values from the complete reduction process were statistically significant. Furthermore, at the same degree of reduction, the comparisons between different disc heights were almost all statistically significant. Intergroup comparisons showed that an increased disc height would cause more tension on the L5-NR in the SG than in the CG. At a 10-mm disc height, all results between the groups demonstrated statistical significance. The slip-angle correction produced a slight increase in the tension on the L5-NR in both groups. CONCLUSIONS: Increased disc height and reduction significantly increased the tension on the L5-NR, which demonstrated a nonlinear curve. The slip-angle correction from 0° to -30° slightly increased the tension on the L5-NR. Under the same degree of reduction and restored disc height, the SG had more tension on the L5-NR than the CG.

Quantitative T1 mapping MRI for the assessment of extraocular muscle fibrosis in thyroid-associated ophthalmopathy.

PURPOSE: We aimed to investigate the performance of T1 mapping and its histological correlation with extraocular muscle fibrosis in thyroid-associated ophthalmopathy (TAO). METHODS: We prospectively recruited 12 cases of active TAO, 12 cases of inactive TAO, and 15 cases of control subjects. All participants underwent magnetic resonance imaging (MRI) scan with pre-/postcontrast T1 mapping and short-time inversion-recovery (STIR) sequence. The images were analyzed to obtain precontrast T1, extracellular-volume (ECV) fraction on T1 mapping, and signal-intensity ratio (SIR) on STIR for each rectus. Muscle biopsy was performed at lateral rectus to quantify-collagen volume fraction, glycosaminoglycan (GAG)-volume fraction, and extracellular space component. The relationship between MRI and histopathology was examined with Pearson correlation coefficient. RESULTS: The active TAO group was characterized with GAG accumulation, while the inactive TAO group presented with substantial fibrosis. The MRI parameters achieved acceptable interobserver and intraobserver agreement. The precontrast T1 and ECV remarkably increased in the TAO groups than the control group, and ECV positively correlated with collagen-volume fraction (r = 0.913) and extracellular-space component (r = 0.886) in the inactive TAO group. The SIR statistically increased in the active TAO group, and SIR positively correlated with GAG-volume fraction in all three groups. The performance of ECV (cutoff > 48.1%) to screen out extraocular muscle fibrosis in inactive TAO was 60.9% sensitivity and 93.3% specificity. CONCLUSIONS: The ECV parameter on T1 mapping MRI is a reliable tool to quantify extraocular muscle fibrosis, providing insights into noninvasive evaluation of pathological changes in TAO orbit. TRIAL REGISTRATION NUMBER: ChiCTR2000040394; Date of registration: 28 November 2020.

Chondrocyte-laden GelMA hydrogel combined with 3D printed PLA scaffolds for auricle regeneration.

The current gold standard for auricular reconstruction after microtia or ear trauma is the autologous cartilage graft with an autologous skin flap overlay. Harvesting autologous cartilage requires an additional surgery that may result in donor area complications. In addition, autologous cartilage is limited and the auricular reconstruction requires complex sculpting, which requires excellent clinical skill and is very time consuming. This work explores the use of 3D printing technology to fabricate bioactive artificial auricular cartilage using chondrocyte-laden gelatin methacrylate (GelMA) and polylactic acid (PLA) for auricle reconstruction. In this study, chondrocytes were loaded within GelMA hydrogel and combined with the 3D-printed PLA scaffolds to biomimetic the biological mechanical properties and personalized shape. The printing accuracy personalized scaffolds, biomechanics and chondrocyte viability and biofunction of artificial auricle have been studied. It was found that chondrocytes were fixed in the PLA auricle scaffolds via GelMA hydrogels and exhibited good proliferative properties and cellular activity. In addition, new chondrocytes and chondrogenic matrix, as well as type II collagen were observed after 8 weeks of implantation. At the same time, the transplanted auricle complex kept full and delicate auricle shape. This study demonstrates the potential of using 3D printing technology to construct in vitro living auricle tissue. It shows a great prospect in the clinical application of auricle regeneration.

Predictive value of pretreatment PD-L1 expression in EGFR-mutant non-small cell lung cancer: a meta-analysis.

OBJECTIVE: To investigate the predictive value of programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). METHODS: We conducted a systemic search of PubMed, EMBASE, and the Cochrane Library from 1 January 2000 to 30 August 2020, to identify related studies. We combined the hazard ratio (HR) and 95% confidence interval (CI) to assess the correlation of PD-L1 expression with progression-free survival (PFS) and overall survival (OS). We assessed the quality of the included studies by the Newcastle-Ottawa Scale (NOS). We performed subgroup analyses based on immunohistochemistry (IHC) scoring system, IHC antibodies, sample size, countries, and survival analysis mode. Sensitivity analysis and evaluation of publication bias were also performed. RESULTS: Twelve studies including 991 patients met the criteria. The mean NOS score was 7.42 ± 1.19. Patients with high PD-L1 expression was associated with poorer PFS (HR = 1.90; 95% CI = 1.16-3.10; P = 0.011), while there was no association between PD-L1 expression and OS (HR = 1.19; 95% CI = 0.99-1.43; P = 0.070). Subgroup analysis prompted IHC scoring systems, IHC antibodies, and sample size have important effects on heterogeneity. The pooled results were robust according to the sensitivity analysis. CONCLUSIONS: The result of this meta-analysis suggested that PD-L1 expression might be a predictive biomarker for EGFR-mutant non-small cell lung cancer treated with EGFR-TKIs.