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Abstract Background To evaluate the changes of retinal and choroidal microvascular including the superficial retinal capillary plexus (SCP), deep retinal capillary plexus (DCP), choriocapillaris (CC), and central retinal thickness (CRT) in high myopic eyes after the implantable collamer lens with a central hole (ICL V4c) implantation using optical coherence tomography angiography (OCTA). Methods This retrospective study included 30 eyes of 30 patients (14 males and 16 females) who underwent ICL V4c implantation in Tianjin Aier Eye Hospital from October 2022 to May 2023. Uncorrected distant visual acuity (UDVA), best corrected distance visual acuity (BDVA), intraocular pressure (IOP), spherical equivalent (SE), axial length (AL), and optical coherence tomography angiography (OCTA) were measured and assessed before surgery, and 1 week, 1 month, and 3 months after surgery. OCTA was used to image and measure several key indicators: the foveal avascular zone (FAZ), vascular density (VD) of the SCP and DCP, blood flow density (BD) of the CC, and CRT. All measurement data were obtained utilizing the instrument’s proprietary software, ensuring accuracy and consistency. Results UDVA were significant improvements at the 1 week, 1 month, and 3 months after ICL V4c implantation surgery. BDVA, FAZ, and CRT maintained stable, however, IOP was higher at 1 week and 3 months post-operation compared to 1-month post-operation. The statistically significant difference was identified within the S3, S7, and S9 of SCP at each time point before and after the surgery (P 1 = 0.004; P 2 = 0.014; P 3 = 0.037). However, paired analyses showed that there was a significant decrease in VD of S3 at 1 week after ICL V4c implantation surgery (P 0.05), and the increase in VD of the S7 region at 1 month after ICL V4c implantation, which is significant compared to 1 week post-surgery, but not compared to preoperative levels. An overall comparison of the BD of the CC (2 mm) at each time point showed a statistically significant difference (P = 0.029). Conclusion ICL V4c implantation offers a safe and efficient therapy to the high myopic patients. However, the retinal and choroidal microvascular changes need to be paid attention to in post-ICL implantation patients.

Abstract Background Manual placement of cervical pedicle screws is risky, and robot-assisted placement of atlantoaxial pedicle screws has not been reported. Case report We describe a 74-year-old female patient with atlantoaxial fracture and dislocation combined with spinal cord injury caused by a car accident. The left lower limb muscle strength was grade 0, the right upper limb muscle strength was grade 1, and the right lower limb muscle strength was grade 2. Loss of sensation below the clavicle level, decreased superficial sensation in the extremities, loss of deep sensation in the left lower extremity, and incontinence were observed. We successfully placed atlas pedicle screws with the assistance of the Mazor X robot. One week after the operation, radiological imaging revealed that the reduction effect was good, the placement of the pedicle screws was satisfactory, the left upper limb and left lower limb muscle strength was level 2, the right upper limb and the muscle strength of the right lower limb were grade 3, and the sensory function was partially restored. No complications related to screw placement were found at the 3-month postoperative follow-up. Conclusions Mazor X robot-assisted descending pedicle screw fixation of the atlas is feasible and safe.

Abstract Background The prognostic potential of immune-related genes, particularly immune checkpoint inhibitors (ICIs) and long non-coding RNAs (lncRNAs), is gaining attention for evaluating the prognosis of breast cancer patients. Methods We analyzed 23 datasets to identify 15 ICI-related mRNAs and 5 immune-related lncRNAs, creating a robust immune score (IS). This score was used to classify patients into high and low IS groups and assess their survival outcomes. Results Patients with high IS showed significantly poorer overall survival (OS) and progression-free survival (PFS) compared to those with low IS. Multivariate Cox regression analysis confirmed IS as an independent prognostic factor. Additionally, high IS was associated with higher mutation loads and neoantigen profiles, while low IS correlated with enhanced immune cell infiltration. Conclusions The immune score developed from ICI-related mRNAs and lncRNAs effectively predicts the prognosis of breast cancer patients and highlights the differential immune and inflammatory responses between patients with varying levels of immune score. This underscores the relevance of IS in guiding therapeutic decisions and tailoring patient management strategies in clinical settings.

Abstract Background Epidermal growth factor receptor (EGFR) fusions are rare but potentially actionable oncogenic drivers across multiple solid tumors. However, the distribution and molecular characteristics of EGFR fusions in Chinese patients with solid malignancies have not been explored. Methods Panel-based next-generation sequencing (NGS) data of 35,023 patients with various types of solid tumors was collected and analyzed from the Simcere Diagnostics (Nanjing, China) database. A 9563-patient cohort was derived from The Cancer Genome Atlas (TCGA) to explore the relationship between EGFR fusion status and overall survival (OS). Results In this study, prevalence of functional EGFR fusions was 0.303% (106/35,023) in total across solid tumors, which occur more commonly in gastroesophageal junction cancer (1/61, 1.613%), followed by medulloblastoma (1/66, 1.515%) and glioma (33/2409, 1.370%). Analysis showed a prevalence for fusion partners in different tumor types. The top 3 co-mutant genes with EGFR fusion were TP53 (mutation frequency, MF: 65%), BRCA2 (MF: 43%), and ALK (MF: 41%). Furthermore, patients in the EGFR fusion group had a significantly shorter OS than those in the non-EGFR fusion group (p

Abstract Background Class III peroxidases (PODs) perform crucial functions in various developmental processes and responses to biotic and abiotic stresses. However, their roles in wheat seed dormancy (SD) and germination remain elusive. Results Here, we identified a wheat class III POD gene, named TaPer12-3A, based on transcriptome data and expression analysis. TaPer12-3A showed decreasing and increasing expression trends with SD acquisition and release, respectively. It was highly expressed in wheat seeds and localized in the endoplasmic reticulum and cytoplasm. Germination tests were performed using the transgenic Arabidopsis and rice lines as well as wheat mutant mutagenized with ethyl methane sulfonate (EMS) in Jing 411 (J411) background. These results indicated that TaPer12-3A negatively regulated SD and positively mediated germination. Further studies showed that TaPer12-3A maintained H2O2 homeostasis by scavenging excess H2O2 and participated in the biosynthesis and catabolism pathways of gibberellic acid and abscisic acid to regulate SD and germination. Conclusion These findings not only provide new insights for future functional analysis of TaPer12-3A in regulating wheat SD and germination but also provide a target gene for breeding wheat varieties with high pre-harvest sprouting resistance by gene editing technology.

Abstract Background B-box (BBX) proteins are a type of zinc finger proteins containing one or two B-box domains. They play important roles in development and diverse stress responses of plants, yet their roles in wheat remain unclear. Results In this study, 96 BBX genes were identified in the wheat genome and classified into five subfamilies. Subcellular localization prediction results showed that 68 TaBBXs were localized in the nucleus. Protein interaction prediction analysis indicated that interaction was one way that these proteins exerted their functions. Promoter analysis indicated that TaBBXs may play important roles in light signal, hormone, and stress responses. qRT-PCR analysis revealed that 14 TaBBXs were highly expressed in seeds compared with other tissues. These were probably involved in seed dormancy and germination, and their expression patterns were investigated during dormancy acquisition and release in the seeds of wheat varieties Jing 411 and Hongmangchun 21, showing significant differences in seed dormancy and germination phenotypes. Subcellular localization analysis confirmed that the three candidates TaBBX2-2 A, TaBBX4-2 A, and TaBBX11-2D were nuclear proteins. Transcriptional self-activation experiments further demonstrated that TaBBX4-2A was transcriptionally active, but TaBBX2-2A and TaBBX11-2D were not. Protein interaction analysis revealed that TaBBX2-2A, TaBBX4-2A, and TaBBX11-2D had no interaction with each other, while TaBBX2-2A and TaBBX11-2D interacted with each other, indicating that TaBBX4-2A may regulate seed dormancy and germination by transcriptional regulation, and TaBBX2-2A and TaBBX11-2D may regulate seed dormancy and germination by forming a homologous complex. Conclusions In this study, the wheat BBX gene family was identified and characterized at the genomic level by bioinformatics analysis. These observations provide a theoretical basis for future studies on the functions of BBXs in wheat and other species.

Abstract Background Our study aimed to analyze the characteristics of ultrasound images corresponding to each histological stage of primary biliary cholangitis (PBC). Methods We prospectively analyzed 75 confirmed cases of PBC and used liver biopsy as the gold standard to determine the disease stage. Results The typical ultrasound images of patients with PBC were characterized by a thickening of the portal vein wall (PVW) and periportal hypoechoic band (PHB) width with increasing histological stages, and significant increases in the left hepatic lobe diameter (LHLD) in stage II (by 64.0%) and stage III (by 69.2%). PHB width (r = 0.857, p

Abstract Background Impaired sensitivity to thyroid hormones is a newly proposed clinical entity associated with hyperuricemia in the subclinical hypothyroid population. However, it is unknown whether the association exists in the euthyroid population. This study aimed to explore the association of impaired sensitivity to thyroid hormones (assessed by the thyroid feedback quantile-based index [TFQI], parametric thyroid feedback quantile-based index [PTFQI], thyrotrophic thyroxine resistance index [TT4RI] and thyroid-stimulating hormone index [TSHI]) with hyperuricemia and quantify the mediating effect of body mass index BMI in the euthyroid population. Methods This cross-sectional study enrolled Chinese adults aged ≥ 20 years who participated in the Beijing Health Management Cohort (2008–2019). Adjusted logistic regression models were used to explore the association between indices of sensitivity to thyroid hormones and hyperuricemia. Odds ratios [OR] and absolute risk differences [ARD] were calculated. Mediation analyses were performed to estimate direct and indirect effects through BMI. Results Of 30,857 participants, 19,031 (61.7%) were male; the mean (SD) age was 47.3 (13.3) years; and 6,515 (21.1%) had hyperuricemia. After adjusting for confounders, individuals in the highest group of thyroid hormone sensitivity indices were associated with an increased prevalence of hyperuricemia compared with the lowest group (TFQI: OR = 1.18, 95% CI 1.04–1.35; PTFQI: OR = 1.20, 95% CI 1.05–1.36; TT4RI: OR = 1.17, 95% CI 1.08–1.27; TSHI: OR = 1.12, 95% CI 1.04–1.21). BMI significantly mediated 32.35%, 32.29%, 39.63%, and 37.68% of the associations of TFQI, PTFQI, TT4RI and TSHI with hyperuricemia, respectively. Conclusions Our research revealed that BMI mediated the association between impaired sensitivity to thyroid hormones and hyperuricemia in the euthyroid population. These findings could provide useful evidence for understanding the interaction between impaired sensitivity to thyroid hormone and hyperuricemia in euthyroid individuals and suggest the clinical implications of weight control in terms of impaired thyroid hormones sensitivity.

Abstract Background Arteriosclerosis and atherosclerosis are closely related with cardiovascular disease (CVD) risk. Remnant cholesterol (RC) could predict CVD. However, its effect on joint arteriosclerosis and atherosclerosis progression remains unclear. This study aims to evaluate the association of RC with joint arteriosclerosis and atherosclerosis progression trajectories in the general population. Methods This study collected data across five biennial surveys of the Beijing Health Management Cohort from 2010 to 2019. Multi-trajectory model was used to determine the joint arteriosclerosis and atherosclerosis progression patterns by brachial-ankle pulse wave velocity (baPWV) and ankle brachial index (ABI). We also performed discordance analyses for RC vs. low density lipoprotein cholesterol (LDL-C) using ordinal logistics model. Results A total of 3186 participants were included, with three clusters following distinct arteriosclerosis and atherosclerosis progression patterns identified using a multi-trajectory model. In the multivariable-adjusted ordinal logistics analyses, RC was significantly associated with baPWV and ABI progression (OR: 1.20; 95% CI: 1.13–1.28, per 10 mg/dL). For the discordance analyses, the discordant low RC group was associated with decreased risk compared to the concordant group (OR: 0.73; 95% CI: 0.60–0.89). People with a high RC level were at an increased risk of joint arteriosclerosis and atherosclerosis progression, even with optimal LDL-C. Conclusions RC is independently associated with joint arteriosclerosis and atherosclerosis progression beyond LDL-C. RC could be an earlier risk factor than LDL-C of arteriosclerosis and atherosclerosis in the general population.

Abstract Background This trial aimed to analyse the safety, effectiveness and transcriptomic characteristics of neoadjuvant toripalimab plus chemotherapy in II–III non-small-cell lung cancer (NSCLC). Methods Patient eligibility mainly involved treatment-naive, clinical stage II–III and wild-type EGFR/ALK NSCLC. The patients received 2–4 cycles of toripalimab (240 mg q3w) plus carboplatin-based chemotherapy. After the second treatment cycle, all patients were re-evaluated by a multidisciplinary team. Candidates eligible for surgery underwent surgery; otherwise, patients received the remaining treatment cycles. The primary endpoints were safety and major pathological response (MPR). Secondary endpoints were R0 resection rate, progression-free survival (PFS) and overall survival (OS). RNA sequencing of baseline and post-treatment samples was conducted to explore the transcriptomic characteristics of the therapeutic response. Results In total, 50 eligible patients were enrolled, including 12 (24.0%) with resectable disease (RD) and 38 (76.0%) with potentially resectable disease (PRD). Treatment-related adverse events (TRAEs) were recorded in 48 cases (96.0%). Severe TRAEs occurred in 3 (6.0%) cases, including myelosuppression, drug-induced liver injury and death related to haemoptysis. The objective response rate (ORR) was 76.0%, with 8 (16.0%) patients having a complete response (CR), 30 (60.0%) partial response (PR), 10 (20.0%) stable disease (SD) and 2 (4.0%) progressive disease (PD). Surgery could be achieved in 12 (100%) patients with RD and 25 (65.8%) with PRD; 1 (2.0%) with PRD refused surgery. Therefore, R0 resection was performed for all 36 (100%) patients who underwent surgery; 20 (55.6%) achieved MPR, including 10 (27.8%) with a complete pathological response (pCR). The CHI3L1 (chitinase-3-like protein 1) immunohistochemistry (IHC) expression of baseline tumour samples could predict the therapeutic response (AUC=0.732), OS (P=0.017) and PFS (P=0.001). Increased PD-1 expression, T cell abundance and immune-related pathway enrichment were observed in post-treatment samples compared to baseline in the response group (CR+PR) but not in the non-response group (SD+PD). Conclusions Neoadjuvant toripalimab plus chemotherapy was safe and effective, with a high MPR and manageable TRAEs for II–III NSCLC, even converting initially PRD to RD. Disparate transcriptomic characteristics of therapeutic efficiency were observed, and CHI3L1 expression predicted therapeutic response and survival. Trial registration ChiCTR1900024014, June 22, 2019.

Abstract Background Arterial stiffness, glycemic control and blood pressure are risk factors of macrovascular complications in type 2 diabetes. This study aimed to investigate the combined association of arterial stiffness, glycemic control and hypertension status with the occurrence of diabetic macrovascular complication. Methods A total of 1870 patients of diabetes were enrolled from Beijing Health Management Cohort between 2008 and 2018 as baseline, and then followed for macrovascular complication onset. We proposed a composite risk score (0–4) by arterial stiffness severity, pool glycemic control and hypertension status. Cox model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI). Results The mean age (SD) of this population was 59.90 (12.29) years. During a median follow-up of 4.0 years, 359 (19.2%) patients developed macrovascular complication. Compared to the normal arterial stiffness and good glycemic control group, patients with severe arterial stiffness and pool glycemic control had the highest risk of macrovascular complications (HR: 2.73; 95% CI: 1.42–5.25). Similarly, those of severe arterial stiffness and hypertension had the highest risk (HR: 2.69; 95% CI: 1.61–4.50). Patients of the composite score > 2 had a significantly increased risk of macrovascular complication. Conclusion This study suggested the clinical importance of combined evaluation of arterial stiffness, glycemic control and hypertension status for the risk stratification and management of macrovascular complication of type 2 diabetes.

Abstract Background Butyrate is a major subgingival microbial metabolite that is closely related to periodontal disease. It affects the proliferation and differentiation of mesenchymal stem cells. However, the mechanisms by which butyrate affects the osteogenic differentiation of periodontal ligament stem cells (PDLSCs) remain unclear. Here, we investigated the effect of sodium butyrate (NaB) on the osteogenic differentiation of human PDLSCs. Methods PDLSCs were isolated from human periodontal ligaments and treated with various concentrations of NaB in vitro. The cell counting kit-8 assay and flow cytometric analysis were used to assess cell viability. The osteogenic differentiation capabilities of PDLSCs were evaluated using the alkaline phosphatase activity assay, alizarin red staining, RT-PCR, western blotting and in vivo transplantation. Results NaB decreased PDLSC proliferation and induced apoptosis in a dose- and time-depend manner. Additionally, 1 mM NaB reduced alkaline phosphatase activity, mineralization ability, and the expression of osteogenic differentiation-related genes and proteins. Treatment with a free fatty acids receptor 2 (FFAR2) antagonist and agonist indicated that NaB inhibited the osteogenic differentiation capacity of PDLSCs by affecting the expression of Smad1. Conclusion Our findings suggest that NaB inhibits the osteogenic differentiation of PDLSCs by activating FFAR2 and decreasing the expression of Smad1.

Abstract Background Seed dormancy and germination determine wheat resistance to pre-harvest sprouting and thereby affect grain yield and quality. Arabidopsis VQ genes have been shown to influence seed germination; however, the functions of wheat VQ genes have not been characterized. Results We identified 65 TaVQ genes in common wheat and named them TaVQ1–65. We identified 48 paralogous pairs, 37 of which had Ka/Ks values greater than 1, suggesting that most TaVQ genes have experienced positive selection. Chromosome locations, gene structures, promoter element analysis, and gene ontology annotations of the TaVQs showed that their structures determined their functions and that structural changes reflected functional diversity. Transcriptome-based expression analysis of 62 TaVQ genes and microarray analysis of 11 TaVQ genes indicated that they played important roles in diverse biological processes. We compared TaVQ gene expression and seed germination index values among wheat varieties with contrasting seed dormancy and germination phenotypes and identified 21 TaVQ genes that may be involved in seed dormancy and germination. Conclusions Sixty-five TaVQ proteins were identified for the first time in common wheat, and bioinformatics analyses were used to investigate their phylogenetic relationships and evolutionary divergence. qRT-PCR data showed that 21 TaVQ candidate genes were potentially involved in seed dormancy and germination. These findings provide useful information for further cloning and functional analysis of TaVQ genes and introduce useful candidate genes for the improvement of PHS resistance in wheat.

Abstract Background To evaluate the association of physical activity (PA) intensity with cognitive performance at baseline and during follow-up. Methods A total of 4039 participants aged 45 years or above from the China Health and Retirement Longitudinal Study were enrolled in visit 1 (2011–2012) and followed for cognitive function in visit 2 (2013–2014), visit 3 (2015–2016), and visit 4 (2017–2018). We analyzed the association of PA intensity with global cognition, episodic memory, and mental intactness at baseline using adjusted regression methods and evaluated the long-term effect of PA intensity using multiple measures of cognition scores by mixed effect model. Results In cross-sectional analysis, mild and moderate PA, rather than vigorous PA, was associated with better cognitive performance. The results remained consistent in multiple sensitivity analyses. During the follow-up, participant with mild PA had a 0.56 (95% CI 0.12–0.99) higher global cognition, 0.23 (95% CI 0.01–0.46) higher episodic memory, and 0.33 (95% CI 0.01–0.64) higher mental intactness, while those with moderate PA had a 0.74 (95% CI 0.32–1.17) higher global score, 0.32 (95% CI 0.09–0.54) higher episodic memory, and 0.43 (95% CI 0.12–0.74) higher mental intactness, compared with individuals without PA. Vigorous PA was not beneficial to the long-term cognitive performance. Conclusions Our study indicates that mild and moderate PA could improve cognitive performance, rather than the vigorous activity. The targeted intensity of PA might be more effective to achieve the greatest cognition improvement considering age and depressive status.

Abstract Background Despite research efforts, the causative factors that contribute to esophageal squamous cell carcinoma (ESCC) in high-risk areas have not yet been understood. In this study, we, therefore, aimed to describe the risk factors associated with ESCC and its precursor lesions. Methods We performed an endoscopic examination of 44,857 individuals aged 40–69 years from five high incidence regions of China in 2017–2018. Participants were classified as 4 groups of normal control, esophagitis, low-grade intraepithelial neoplasia (LGIN) and high-grade intraepithelial neoplasia/esophageal squamous cell carcinoma (HGIN/ESCC) using an unconditional logistic regression determine risk factors. Results We identified 4890 esophagitis, 1874 LGIN and 437 HGIN/ESCC cases. Crude odds ratios (ORs) and adjusted odds ratios were calculated using unconditional logistic regression. Drinking well and surface water, salty diet, and positive family history of cancer were the common risk factors for esophagitis, LGIN and HGIN/ESCC. History of chronic hepatitis/cirrhosis was the greatest risk factor of esophagitis (adjusted OR 2.96, 95%CI 2.52–3.47) and HGIN/ESCC (adjusted OR 1.91, 95%CI 1.03–3.22). Pesticide exposure (adjusted OR 1.20, 95%CI 1.05–1.37) was essential risk factor of LGIN. Conclusions Among individuals aged 40–69 years in high incidence regions of upper gastrointestinal cancer, the results provided important epidemiological evidence for the prevention of different precancerous lesions of ESCC.

Abstract Background The purpose of the current study was to explore the role and underlying mechanism of cellular retinoic acid binding protein 2 (CRABP2) in dexamethasone (DEX)-induced apoptosis in human osteoblast cells. Methods GSE10311 was downloaded from the Gene Expression Omnibus (GEO) database to identify the differentially expressed genes (DEGs) by the limma/R package. Primary human osteoblast was isolated and treated with different concentration of DEX (0, 10-8, 10-7, 10-6, 10-5, and 10-4 mol/L), and cell viability and flow cytometry were used to detect cell proliferation and apoptosis. A CRABP2 overexpression plasmid (oe-CRABP2) was used to overexpress CRABP2, and western blotting was conducted to detect protein expression. Results We found that CRABP2 was downregulated in the DEX-treated group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that DEGs were associated with PI3K/Akt signaling pathway. DEX downregulated CRABP2 gene and protein expression, inhibited viability, and induced human osteoblast apoptosis. Overexpression of CRABP2 reversed DEX-induced apoptosis in human osteoblast. Moreover, overexpression of CRABP2 delayed the progression of DEX-induced osteonecrosis of the femoral head (ONFH) animal model. Conclusion In conclusion, CRABP2 is effective at inhibiting DEX-induced human osteoblast apoptosis and delayed ONFH progression.

Abstract Background The purpose of this study is to evaluate a new method involving time maximum intensity projection (t-MIP) postprocessed from dynamic computed tomographic angiography (dyn-CTA) in diagnosing peripheral arterial disease (PAD). Methods A population of 34 patients with known PAD was examined with a combined CTA protocol consisting of a standard CTA (s-CTA) scan of the lower extremities and a dyn-CTA scan of the calves. For each lower leg, t-MIP images consisting of the MIP0 (sagittal MIP), MIP+θ (45° lateral MIP), and MIP−θ (− 45° lateral MIP) were automatically generated from dyn-CTA. An objective evaluation of the vascular CT attenuation of the best enhancement phase of dyn-CTA and t-MIP was measured; a subjective evaluation of vessel stenosis and occlusion was performed, assigning a score for t-MIP and s-CTA. The CT attenuation of t-MIP and dyn-CTA was compared, as were the runoff scores of t-MIP and s-CTA. Results The CT attenuation of t-MIP CTA of three vascular segments from 68 lower extremities was higher than that of the best enhancement phase of dyn-CTA and s-CTA, with statistically significant differences at the posterior tibial artery and fibular artery (all p

Abstract Background A number of studies have reported hyperprogressive disease (HPD) in non-small cell lung cancer (NSCLC) after treatment with immune checkpoint inhibitor (ICI). This study aimed to summarize the incidence and survival outcome of HPD in NSCLC and identify the clinicopathological features associated with HPD based on available eligible studies. Methods Four databases (Medline/PubMed, Embase, Web of Science, and Cochrane Library) were searched for eligible studies on HPD published before January 23, 2020, to evaluate the incidence, outcome, and clinical features of HPD. Statistical analyses were performed using STATA 15.0. All meta-analyses were performed based on the random-effects model. Results This study included 6 studies involving 1389 patients. The incidence of HPD ranged from 8.02 to 30.43%. Compared with patients with non-HPD, those with HPD were associated with worse overall survival. We identified that Eastern Cooperative Oncology Group > 1, Royal Marsden Hospital score ≥ 2, serum lactate dehydrogenase > upper limit of normal, the number of metastasis sites > 2, and liver metastasis were associated with the risk of HPD. Conclusions This study summarized the clinical features of HPD in NSCLC patients. The meta-analysis showed that five pre-treatment clinicopathological features might be associated with HPD, which may help in selecting patients for ICIs.

Abstract Background During human pregnancy, placental trophectoderm cells release extracellular vesicles (EVs) into maternal circulation. Trophoblasts also give rise to cell-free DNA (cfDNA) in maternal blood, and has been used for noninvasive prenatal screening for chromosomal aneuploidy. We intended to prove the existence of DNA in the EVs (evDNA) of maternal blood, and compared evDNA with plasma cfDNA in terms of genome distribution, fragment length, and the possibility of detecting genetic diseases. Methods Maternal blood from 20 euploid pregnancies, 9 T21 pregnancies, 3 T18 pregnancies, 1 T13 pregnancy, and 2 pregnancies with FGFR3 mutations were obtained. EVs were separated from maternal plasma, and confirmed by transmission electronic microscopy (TEM), western blotting, and flow cytometry (FACS). evDNA was extracted and its fetal origin was confirmed by quantitative PCR (qPCR). Pair-end (PE) whole genome sequencing was performed to characterize evDNA, and the results were compared with that of cfDNA. The fetal risk of aneuploidy and monogenic diseases was analyzed using the evDNA sequencing data. Results EVs separated from maternal plasma were confirmed with morphology by TEM, and protein markers of CD9, CD63, CD81 as well as the placental specific protein placental alkaline phosphatase (PLAP) were confirmed by western blotting or flow cytometry. EvDNA could be successfully extracted for qPCR and sequencing from the plasma EVs. Sequencing data showed that evDNA span on all 23 pairs of chromosomes and mitochondria, sharing a similar distribution pattern and higher GC content comparing with cfDNA. EvDNA showed shorter fragments yet lower fetal fraction than cfDNA. EvDNA could be used to correctly determine fetal gender, trisomies, and de novo FGFR3 mutations. Conclusions We proved that fetal DNA could be detected in EVs separated from maternal plasma. EvDNA shared some similar features to plasma cfDNA, and could potentially be used to detect genetic diseases in fetus.

Abstract Background Surgical treatment is mainly used for atlantoaxial tuberculosis with neurological damage. However, the anatomic structure around the atlantoaxial joint is complex, and the position of vertebral body is deep, which increases the difficulty of the operation and it is challenging for the surgeon to develop surgical strategy. The purpose of this study was to evaluate the clinical outcomes of one-stage combined anterior and posterior surgical treatment approach for atlantoaxial tuberculosis with neurological impairment. Methods From January 2005 to January 2015, 12 patients suffering from atlantoaxial tuberculosis with neurological impairment were surgically treated by one-stage combined anterior and posterior approach. Preoperative CT scanning and MRI imaging showed unilateral or bilateral lateral mass destruction of the atlas, and varying destruction degrees of odontoid process, loss of atlantoaxial stability, and tuberculosis focus into the spinal canal resulting in the corresponding spinal cord compression in all patients. The preoperative neurological classifications were Class C for 4 cases, D for 8 cases according to the American Spinal Injury Association (ASIA) system. Quadruple sensitive anti-TB drug treatment was used in all 12 patients preoperative and postoperative. Patients’ clinical symptoms and neurological function recovery were evaluated by comparing the Visual Analogue Scale (VAS) score, Neck Disability Index (NDI), Japanese Orthopedic Association (JOA) score and ASIA grading before operation and at the final follow-up. Results Mean surgical duration was 263.3 ± 43.6 min. Intraoperative blood loss was averagely 529.2 ± 169.8 ml. The average fusion period was 7.3 ± 1.5 months. No instrumentation loosening, migration or breakage was observed during the follow-up of 6.5 ± 2.9 years. The VAS, NDI and JOA scores were significantly changed to 1.00 ± 0.95, 9.50 ± 3.34 and 15.42 ± 1.44 at last follow-up (P