A nomogram based on the quantitative and qualitative features of CT imaging for the prediction of the invasiveness of ground glass nodules in lung adenocarcinoma.

PURPOSE: Based on the quantitative and qualitative features of CT imaging, a model for predicting the invasiveness of ground-glass nodules (GGNs) was constructed, which could provide a reference value for preoperative planning of GGN patients. MATERIALS AND METHODS: Altogether, 702 patients with GGNs (including 748 GGNs) were included in this study. The GGNs operated between September 2020 and July 2022 were classified into the training group (n = 555), and those operated between August 2022 and November 2022 were classified into the validation group (n = 193). Clinical data and the quantitative and qualitative features of CT imaging were harvested from these patients. In the training group, the quantitative and qualitative characteristics in CT imaging of GGNs were analyzed by using performing univariate and multivariate logistic regression analyses, followed by constructing a nomogram prediction model. The differentiation, calibration, and clinical practicability in both the training and validation groups were assessed by the nomogram models. RESULTS: In the training group, multivariate logistic regression analysis disclosed that the maximum diameter (OR = 4.707, 95%CI: 2.06-10.758), consolidation/tumor ratio (CTR) (OR = 1.027, 95%CI: 1.011-1.043), maximum CT value (OR = 1.025, 95%CI: 1.004-1.047), mean CT value (OR = 1.035, 95%CI: 1.008-1.063; P = 0.012), spiculation sign (OR = 2.055, 95%CI: 1.148-3.679), and vascular convergence sign (OR = 2.508, 95%CI: 1.345-4.676) were independent risk parameters for invasive adenocarcinoma. Based on these findings, we established a nomogram model for predicting the invasiveness of GGN, and the AUC was 0.910 (95%CI: 0.885-0.934) and 0.902 (95%CI: 0.859-0.944) in the training group and the validation group, respectively. The internal validation of the Bootstrap method showed an AUC value of 0.905, indicating a good differentiation of the model. Hosmer-Lemeshow goodness of fit test for the training and validation groups indicated that the model had a good fitting effect (P > 0.05). Furthermore, the calibration curve and decision analysis curve of the training and validation groups reflected that the model had a good calibration degree and clinical practicability. CONCLUSION: Combined with the quantitative and qualitative features of CT imaging, a nomogram prediction model can be created to forecast the invasiveness of GGNs. This model has good prediction efficacy for the invasiveness of GGNs and can provide help for the clinical management and decision-making of GGNs.

Efficacy and safety of thalidomide in children with monogenic autoinflammatory diseases: a single-center, real-world-evidence study.

BACKGROUND: Monogenic autoinflammatory diseases (AIDs) are rare inflammatory diseases caused by genetic variants. The pathogenesis is complex and treatment options are limited. This study aimed to describe the safety and efficacy of thalidomide in the treatment of monogenic AIDs. METHODS: This was a single-center, single-arm, real-world study. From September 2016 to August 2021, patients with monogenic AIDs who met the inclusion and exclusion criteria were given thalidomide for 12 months. There was a 3-month run-in period before dosing. The efficacy and adverse events were evaluated and recorded every 3 months. After 3 and 12 months of thalidomide treatment, clinical manifestations, disease activity score, inflammatory markers, and background medication adjustments were compared with baseline for efficacy analyses. RESULTS: A total of 16 patients entered this study, including 3 with Aicardi-Goutières syndrome (AGS), 4 Blau syndrome, 2 chronic infantile neurologic cutaneous articular syndrome (CINCA), 2 A20 haploinsufficiency (HA20), 1 adenosine deaminase 2 deficiency(DADA2), 1 familial Mediterranean fever (FMF),1 tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS), 1 PLCγ2-associated antibody deficiency and immune dysregulation (PLAID), and 1 stimulator of interferon genes-associated vasculopathy with onset in infancy(SAVI). The efficacy rate in the 16 patients after 3-month and 12-month thalidomide treatment in patients was 56.3%. Twelve patients completed the study, the fever improved in all of them, rash improved in 7 patients, and 5 patients stopped using glucocorticoids or other immunosuppressive agents. C-reactive protein was normal in 8 patients and erythrocyte sedimentation rate was normal in 11 patients. Anorexia and nausea occurred in 2 cases, with no other reported drug-related adverse reactions. CONCLUSION: The largest cohort of monogenic AIDs with the treatment of thalidomide demonstrated that thalidomide can help reduce disease activity and inflammation, reduce the dosage of glucocorticoids, and improve clinical outcomes. Thalidomide is relatively safe in monogenic AIDs.

Rapid ultra-performance liquid chromatography-tandem mass spectrometry method for the simultaneous determination of three characteristic urinary saccharide metabolites in patients with glycogen storage diseases (type â b and â ¡).

Urinary 1,5-anhydroglucitol (1, 5-AG), 6-α-D-glucopyranosyl-maltotriose (Glc4) and maltotetraose (M4) are important biomarkers for glycogen storage disease (types Ib and Ⅱ). This study aimed to develop and validate an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to detect these three urinary saccharide metabolites. Urine samples were diluted and then analyzed. Chromatographic separation was performed on an Acquity™ UPLC Amide column (2.1 × 100 mm, 1.7 µm) with gradient elution. The quantitation of analytes was achieved on a 5500 Qtrap mass spectrometer using negative multiple reaction monitoring (MRM) mode. The calibration curves for all analytes were linear over the range of 0.500 to 100 µg/mL with a correlation coefficient, R2 ≥ 0.999. The percent relative standard deviations (RSD%) were ≤12.8%, and the percent relative errors (RE%) were in the range of -11.7%-11.0%. The relative matrix effects of all analytes were between 87.2% and 104% with RSD% < 3.10% across three concentrations. The developed analytical method was simple, accurate, and reliable for rapid and simultaneous analysis of these three urinary saccharide metabolites. It was applied to healthy volunteers and patients. To our knowledge, it was the first validated assay for urinary maltotetraose quantification. This work provides support for exploring the potential of maltotetraose as a biomarker for Pompe disease.

Development of a rapid simultaneous assay of two urinary tetrasaccharide metabolites using differential ion mobility and tandem mass spectrometry and its application to patients with glycogen storage disease (type Ib and II).

Glucose tetrasaccharide (Glc4) and maltotetraose (M4) are important biomarkers for Pompe disease and other glycogen storage diseases (GSDs). With the development of new treatments for GSDs, more specific and sensitive bioanalytical methods are needed to determine biomarkers. In recent years, differential mobility spectrometry (DMS) has become an effective analytical technique with high selectivity and specificity. This study aimed to develop an efficient analytical method for the two urinary tetrasaccharide metabolites using DMS and apply it to patients with GSDs (type Ib and II). Urine samples were directly diluted and injected into liquid chromatography-differential mobility spectrometry tandem mass spectrometry (LC-DMS-MS/MS). Chromatographic separation was performed on an Acquity™ UPLC BEH Amide column (2.1 × 50 mm, 1.7 µm) with a short gradient elution of 2.6 min. DMS-MS/MS was used to detect two urinary tetrasaccharide metabolites in a negative multiple reaction monitoring mode with isopropanol as a modifier. A total of 20 urine samples from 6 healthy volunteers and 10 patients with GSDs (type Ib and II) were collected for analysis. The method was linear over a concentration range of 0.5~100.0 µg/mL for each urinary tetrasaccharide (r≥0.99). The intra- and inter-day precision RSD% were less than 14.3%, and the accuracy RE% were in the range of -14.3~13.4%. The relative matrix effect was between 86.6 and 114.3%. No carryover or interference was observed. Patients with GSDs (type Ib and II) had significantly higher median urinary Glc4 (P=0.001) and M4 (P=0.012) excretion than healthy subjects. The developed method was simple, rapid, sensitive, and specific. It was successfully applied to healthy volunteers and patients with GSDs (type Ib and II). DMS technology greatly improved analysis efficiency and provided high sensitivity and specificity.

Case report: Multiple arterial stenoses induced by autosomal-recessive hypophosphatemic rickets type 2 associated with mutation of ENPP1: a case study.

Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1)-related multiple arterial stenoses is a rare clinical syndrome in which global arterial calcification begins in infancy, with a high probability of early mortality, and hypophosphatemic rickets develops later in childhood. The vascular status of an ENPP1-mutated patient when they enter the rickets phase has not been thoroughly explored. In this study, we presented a case of an adolescent with an ENPP1 mutation who complained of uncontrolled hypertension. Systematic radiography showed renal, carotid, cranial, and aortic stenoses as well as random calcification foci on arterial walls. The patient was incorrectly diagnosed with Takayasu's arteritis, and cortisol therapy had little effect on reducing the vascular stenosis. As a result, phosphate replacement, calcitriol substitution, and antihypertensive medication were prescribed, and the patient was discharged for further examination. This research presented the vascular alterations of an ENPP1-mutanted patient, and while there is less calcification, intimal thickening may be the primary cause of arterial stenosis.

Clinical phenotypes and prognosis of cytomegalovirus infection in the pediatric systemic lupus erythematosus: a longitudinal analysis.

BACKGROUND: Cytomegalovirus (CMV) plays an important role in the pathogenesis of systemic lupus erythematosus (SLE). However, it is not clear whether the anti-CMV treatment has an impact on the prognosis of SLE patients with CMV infection. We aimed to analyze the clinical characteristics and prognosis of CMV infection in pediatric SLE (pSLE) and to evaluate the effect of anti-CMV treatment on pSLE outcome. METHODS: A retrospective study including 146 pSLE from 2012 to 2021 was conducted. CMV-positive and CMV-negative groups were compared by univariate analysis and stepwise logistic multiple regression to analyze the clinical characteristics of CMV infection in pSLE. Generalized estimating equations (GEE) were used to model the longitudinal dynamics of pSLE disease activity with or without CMV infection and anti-CMV treatment. RESULTS: The CMV infection rate was 74.7% (109/146) in this pSLE cohort. CMV-positive pSLE patients were more likely to present positive anti-dsDNA antibody, hypocomplementemia, high SLEDAI-2K score and musculoskeletal involvement (P < 0.05). Survival analysis showed that CMV-positive pSLE patients were more prone to disease flare and poorer outcomes. GEE modeling indicated that CMV phosphoprotein 65 (pp65) titers were positively correlated with SLEDAI-2K, and anti-CMV treatment could better reduce pSLE activity than non-treatment (P < 0.05). CONCLUSIONS: CMV infection is highly prevalent among pSLE patients. Positive anti-dsDNA antibody, hypocomplementemia, high SLEDAI-2K score and musculoskeletal involvement were significant clinical clues indicating CMV infections in pSLE. CMV infection is correlated with higher disease activity and poorer outcome. Anti-CMV treatment can reduce disease activity and flares.

Phenotypic and genetic characteristics of 130 patients with mucopolysaccharidosis type II: A single-center retrospective study in China.

Background: Mucopolysaccharidosis Type II (MPS II) is a rare, progressive and ultimately fatal X-linked lysosomal storage disorder caused by mutations in the iduronate-2-sulfatase (IDS) gene. This report conducted a retrospective analysis to investigate the clinical characteristics, genotypes and management strategies in a large cohort of Chinese patients with MPS II. Methods: In this study, we explored 130 Chinese patients with MPS II between September 2008 and April 2022. Clinical manifestations, auxiliary examination, IDS pathogenic gene variants and IDS enzyme activity, surgical history were analysed in the study. Results: A total of 130 patients were enrolled and the mean age at diagnosis was 5 years old. This study found the most common symptoms in our patients were claw-like hands, followed by coarse facial features, birthmarks (Mongolian spot), delayed development, inguinal or umbilical hernia. The most commonly cardiac manifestations were valve abnormalities, which were mitral/tricuspid valve regurgitation (71.9%) and aortic/pulmonary valve regurgitation (36.8%). We had found 43 different IDS pathogenic gene variants in 55 patients, included 16 novel variants. The variants were concentrated in exon 9 (20% = 11/55), exon 3 (20% = 11/55) and exon 8 (15% = 8/55). A total of 50 patients (38.5%) underwent surgical treatment, receiving a total of 63 surgeries. The average age of first surgery was 2.6 years, and the majority of surgery (85.7%, 54/63) was operated before 4 years old. The most common and earliest surgery was hernia repair. Three patients were died of respiratory failure. Conclusion: This study provided additional information on the clinical, cardiac ultrasound and surgical procedure in MPS II patients. Our study expanded the genotype spectrum of MPS II. Based on these data, characterization of MPS II patients group could be used to early diagnosis and treatment of the disease.

Early recombinant human growth hormone treatment improves mental development and alleviates deterioration of motor function in infants and young children with Prader-Willi syndrome.

BACKGROUND: Recombinant human growth hormone (rhGH) therapy has shown to improve height and body composition in children with Prader-Willi syndrome (PWS), the evidence of early rhGH treatment on motor and mental development is still accumulating. This study explored the time effect on psychomotor development, anthropometric indexes, and safety for infants and young children with PWS. METHODS: A phase 3, single-arm, multicenter, self-controlled study was conducted in six sites. Patients received rhGH at 0.5 mg/m2/day for first four weeks, and 1 mg/m2/day thereafter for up to 52 weeks. Motor development was measured using Peabody Developmental Motor Scales-second edition, mental development using Griffiths Development Scales-Chinese (GDS-C). Height standard deviation score (SDS), body weight SDS, and body mass index (BMI) SDS were also assessed. RESULTS: Thirty-five patients were enrolled totally. Significant improvements were observed in height, body weight, and BMI SDS at week 52; GDS-C score showed significant improvement in general quotient (GQ) and sub-quotients. In a linear regression analysis, total motor quotient (TMQ), gross motor quotient (GMQ), and fine motor quotient were negatively correlated with age; however, treatment may attenuate deterioration of TMQ and GMQ. Changes in GQ and locomotor sub-quotient in < 9-month group were significantly higher than ≥ 9-month group. Mild to moderate severity adverse drug reactions were reported in six patients. CONCLUSION: Fifty-two-week treatment with rhGH improved growth, BMI, mental development, and lessened the deterioration of motor function in infants and young children with PWS. Improved mental development was more pronounced when instituted in patients < 9 months old.

MTA1-TJP1 interaction and its involvement in non-small cell lung cancer metastasis.

Distant metastasis is the main cause of death in non-small cell lung cancer (NSCLC) patients. The mechanism of metastasis-associated protein 1(MTA1) in NSCLC has not been fully elucidated. This study aimed to reveal the mechanism of MTA1 in the invasion and metastasis of NSCLC. Bioinformatics analysis and our previous results showed that MTA1 was highly expressed in NSCLC tissues and correlated with tumor progression. Knockout of MTA1 by CRISPR/Cas9 significantly inhibited the migration and invasion of H1299 cells, but enhanced cell adhesion. Stable overexpression of MTA1 by lentivirus transfection had opposite effects on migration, invasion and adhesion of A549 cells. The results of in vivo experiments in nude mouse lung metastases model confirmed the promotion of MTA1 on invasion and migration. Tight junction protein 1 (TJP1) was identified by immunoprecipitation and mass spectrometry as an interacting protein of MTA1 involved in cell adhesion. MTA1 inhibited the expression level of TJP1 protein and weakened the tight junctions between cells. More importantly, the rescue assays confirmed that the regulation of MTA1 on cell adhesion, migration and invasion was partially attenuated by TJP1. In Conclusion, MTA1 inhibits the expression level of TJP1 protein co-localized in the cytoplasm and membrane of NSCLC cells, weakens the tight junctions between cells, and changes the adhesion, migration and invasion capabilities of cells, which may be the mechanism of MTA1 promoting the invasion and metastasis of NSCLC. Thus, targeting the MTA1-TJP1 axis may be a promising strategy for inhibiting NSCLC metastasis.

The prognostic value of N6-methyladenosine RBM15 regulators in lung adenocarcinoma.

N6-methyladenosine (m6A) is the most common internal modification in mammalian mRNAs while RNA-binding motif protein 15 (RBM15) is an important methyltransferase in m6A modification. Increasing evidences have shown that RBM15 has a close correlation with lung cancer. However, specific functions of RBM15 in lung adenocarcinoma (LUAD) are limited. RBM15 expression was analyzed in human LUAD tissues and matched healthy lung tissue. RBM15 was knocked down via siRNA in A549 and H1734 cells. The relationships between RBM15 with cellular functions characteristics and mRNA m6A levels were explored. We performed functional characterization in A549 and H1734 cells lines to elucidate the molecular role of RBM15. Results found that RBM15 was up-regulated in the LUAD tissue and cells, which was linked to poor survival of LUAD patients. RBM15 can be knocked down via siRNA in A549, which leads to the exploration of the associations between RBM15 with cell characteristics. In vivo, RBM15 knockdown could decrease the methylation level, reduce proliferation, accelerate apoptosis and inhibit tumor growth. Our research shows that RBM15 facilitates LUAC cell progression by m6A demethylation. However, it is necessary to conduct further researches on potential downstream molecular mechanisms and m6A modification of RBM15 activity in LUAC.

Clinical and genetic spectrum of 14 cases of NLRP3-associated autoinflammatory disease (NLRP3-AID) in China and a review of the literature.

BACKGROUND: NLRP3-associated autoinflammatory disease (NLRP3-AID), caused by mutations of NLRP3, is one of the autoinflammatory diseases affecting inflammasomes. Since there are little cases of Chinese NLRP3-AID, we reported 14 Chinese NLRP3-AID patients in our center and summarized the clinical features of all Chinese patients by reviewing the literature. RESULTS: Fourteen patients had been diagnosed as NLRP3-AID in our center. 12 different NLRP3 variants were identified, among which one is novel: p.Leu361Trp. Rash, recurrent fever, arthritis/arthralgia, uveitis, sensorineural deafness, symptoms of central neural systems (CNS), and increased inflammatory markers (including CRP, ESR, except Ferritin) were the common findings in Chinese patients. The frequencies of fever, neurological symptoms, musculoskeletal manifestations and ocular manifestations in Chinese patients might differ from that of patients from other regions. Besides, we also found clubbing fingers and optic neuritis in some NLRP3-AID patients, which were not commonly mentioned in previous reports. CONCLUSION: In our study, we expanded the clinical spectrum as well as the genetic pathogenic variants of NLRP3-AID. We also found that there were some differences between Chinese patients and patients from other regions, and that Chinese patients were more likely to develop severe symptoms.

Analysis of clinical characteristics of children with Aicardi-Goutieres syndrome in China.

BACKGROUND: Aicardi-Goutieres syndrome (AGS) is an inflammatory disorder belonging to the type I interferonopathy group. The clinical diagnosis of AGS is difficult, which can lead to a high mortality rate. Overall, there is a lack of large-sample research data on AGS in China. We aim to summarize the clinical characteristics of Chinese patients with AGS and provide clues for clinical diagnostic. METHODS: The genetic and clinical features of Chinese patients with AGS were collected. Real-time polymerase chain reaction was used to detect expression of interferon-stimulated genes (ISGs). RESULTS: A total of 23 cases were included, consisting of 7 cases of AGS1 with three prime repair exonuclease 1 mutations, 3 of AGS2 with ribonuclease H2 subunit B (RNASEH2B) mutations, 3 of ASG3 with RNASEH2C, 1 of AGS4 with RNASEH2A mutations, 2 of AGS6 with adenosine deaminase acting on RNA 1 mutations, and 7 of AGS7 with interferon induced with helicase C domain 1 mutations. Onset before the age of 3 years occurred in 82.6%. Neurologic involvement was most common (100%), including signs of intracranial calcification which mainly distributed in the bilateral basal ganglia, leukodystrophy, dystonia, epilepsy, brain atrophy and dysphagia. Intellectual disability, language disability and motor skill impairment were also observed. Skin manifestations (60.87%) were dominated by a chilblain-like rash. Features such as microcephaly (47.62%), short stature (52.38%), liver dysfunction (42.11%), thyroid dysfunction (46.15%), positive autoimmune antibodies (66.67%), and elevated erythrocyte sedimentation rate (53.85%) were also found. The phenotypes of 2 cases fulfilled the diagnostic criteria for systemic lupus erythaematosus (SLE). One death was recorded. ISGs expression were elevated. CONCLUSIONS: AGS is a systemic disease that causes sequelae and mortality. A diagnosis of AGS should be considered for patients who have an early onset of chilblain-like rash, intracranial calcification, leukodystrophy, dystonia, developmental delay, positive autoimmune antibodies, and elevated ISGs, and for those diagnosed with SLE with atypical presentation who are nonresponsive to conventional treatments. Comprehensive assessment of vital organ function and symptomatic treatment are important.

[Simulation of the responses of spring wheat yield to the rates and depths of nitrogen application in dryland based on APSIM model]. / 基于APSIM模型的旱地春小麦产量对施氮量和施氮深度的响应模拟.

Nitrogen limitation is an important factor for the improvement of crop water production potential in rain-fed areas of the Loess Plateau. The reasonable deep application of nitrogen fertilizer is a promising method to increase yield of rain-fed crop. Based on APSIM model, this study simulated spring wheat yield under different nitrogen application rates and depths, by using meteorological observation data from 1990 to 2020 in the semiarid areas of central Gansu Province, aiming to provide theoretical reference for optimizing wheat fertilization strategy. The results showed that the determination coefficient of simulated spring wheat yield, biomass and soil water content in 0-200 cm soil profile was greater than 0.80, the normalized root mean square error was less than 0.2, and the model validity index was greater than 0.5. These results indicated that the model had good fitting and adaptability in the test area. Across all the levels within the experimental design, increasing nitrogen application rates could significantly increase the yield of spring wheat in different precipitation years, and increasing nitrogen application depth could significantly increase spring wheat yield in wet and normal years, but had no effect in dry years. The rate and depth of nitrogen application had significant interaction effects on spring wheat yield in wet and normal years, but not in dry years. According to the binary quadratic regression fitting equation, when the potential maximum yield reached 2749 kg·hm-2 in wet year, nitrogen application depth was 22.7 cm, and nitrogen application rate was 245 kg·hm-2. When the maximum potential yield reached 2596 kg·hm-2 in normal year, nitrogen application depth was 20.6 cm, and nitrogen application rate was 235 kg·hm-2. Integrating the effects of nitrogen application rate and depth on yield, biomass and agronomic efficiency of nitrogen fertilizer, and farmer's fertilizer application habits, the recommended nitrogen application depth was 20-23 cm, and nitrogen application amount was 120-150 kg·hm-2, which could further improve water productivity and nitrogen use efficiency of spring wheat in arid areas of central Gansu Province.

Janus Kinase Inhibitors in the Treatment of Type I Interferonopathies: A Case Series From a Single Center in China.

Objective: This study aimed to assess the efficacy and safety of 2 Janus kinase (JAK) inhibitors (jakinibs) tofacitinib and ruxolitinib in the treatment of type I interferonopathies patients including STING-associated vasculopathy with onset in infancy (SAVI), Aicardi-Goutières syndrome (AGS), and spondyloenchondrodysplasia with immune dysregulation (SPENCD). Methods: A total of 6 patients were considered in this study: 2 patients with SAVI, 1 patient with AGS1, 1 patient with AGS7, and 2 patients with SPENCD. Clinical manifestations, laboratory investigations, radiology examinations, treatment, and outcomes were collected between November 2017 and November 2021 in Peking Union Medical College Hospital. The disease score for patients with SAVI and AGS scale for patients with AGS were documented. The expression of 6 interferon-stimulated genes (ISGs) was assessed by real-time PCR. Results: Three patients (1 patient with SAVI, 2 patients with AGS) were treated with ruxolitinib and 3 patients (1 patient with SAVI, 2 patients with SPENCD) were treated with tofacitinib. The mean duration of the treatment was 2.5 years (1.25-4 years). Upon treatment, cutaneous lesions and febrile attacks subsided in all affected patients. Two patients discontinued the corticoid treatment. Two patients with SAVI showed an improvement in the disease scores (p < 0.05). The erythrocyte sedimentation rate normalized in 2 patients with AGS. The interferon score (IS) was remarkably decreased in 2 patients with SPENCD (p < 0.01). Catch-ups with growth and weight gain were observed in 3 and 2 patients, respectively. Lung lesions improved in 1 patient with SAVI and remained stable in 3 patients. Lymphopenia was found in 3 patients during the treatment without severe infections. Conclusion: The JAK inhibitors baricitinib and tofacitinib are promising therapeutic agents for patients with SAVI, AGS, and SPENCD, especially for the improvement of cutaneous lesions and febrile attacks. However, further cohort studies are needed to assess the efficacy and safety.

MTA1 Expression Can Stratify the Risk of Patients with Multifocal Non-Small Cell Lung Cancers ≤3 cm.

PURPOSE: Currently, there is no uniform standard to guide postoperative adjuvant chemotherapy for patients with multifocal non-small cell lung cancers (NSCLCs) ≤3 cm. Therefore, there is an urgent need to explore prognostic molecular markers to identify high-risk patients with multifocal NSCLCs ≤3 cm. We aimed to explore the potential value of metastasis-associated protein 1(MTA1) expression in risk stratification of patients with multifocal NSCLCs ≤3 cm. METHODS: We retrospectively analyzed the clinical data and postoperative survival data of patients with multifocal NSCLCs ≤3 cm. Paraffin-embedded tissue sections were used for immunohistochemistry. Semiquantitative immunoreactivity scoring (IRS) system was used to evaluate the nuclear expression of MTA1. SPSS software (version 23.0) was used to analyze the data. RESULTS: The IRS of MTA1 nuclear expression in 259 lesions of 119 patients ranged from 2.2 to 11.7 (median: 5.6). Our results showed that MTA1 expression was highest in high-risk pathological subtypes of lung adenocarcinoma. MTA1 expression in multiple primary lung cancers (MPLCs) was lower than that in intrapulmonary metastases (IPMs). The median follow-up duration was 25.97 months. The disease-free survival (DFS) of patients with MPLCs was significantly better than that of patients with IPMs, and the DFS of patients with high MTA1 expression was significantly worse than that of patients with low MTA1 expression. Multivariate Cox analysis showed that high MTA1 expression (hazard ratio: 7.937, 95% confidence interval: 2.433-25.64, p =0.001) was a statistically significant predictor of worse DFS in patients with multifocal NSCLCs ≤3 cm. CONCLUSION: MTA1 expression can stratify the risk in patients with multifocal NSCLCs ≤3 cm. Patients with MTA1 immunohistochemical score >5.6 are at a high risk of postoperative recurrence, and these patients may benefit from postoperative adjuvant chemotherapy.

A novel MAGED2 variant in a Chinese preterm newborn with transient antenatal Bartter's syndrome with 4 years follow-up.

BACKGROUND: Transient antenatal Bartter's syndrome caused by MAGED2 mutation is a rare X-linked recessive renal tubular disorder. Cases reported are mostly infants, and the long-term prognosis of the disease is still under investigation. CASE PRESENTATION: We encountered a preterm male infant with polyhydramnios, polyuria, salt loss, hypercalciuria, nephrocalcinosis and alkalosis. Antenatal Bartter's syndrome was suspected, but these clinical symptoms surprisingly disappeared after about 2 months. This led to the clinical diagnosis of transient antenatal Bartter's syndrome. Gene analysis in this patient disclosed a novel variant (c.1598C > T, p.Ala533Val) in exon 12 of MAGED2 gene, and his mother was a heterozygous carrier. This patient was followed up in clinic for 4 years without recurrence of imbalance of potassium, sodium and chloride. His height and weight were in normal range, and all laboratory examinations and nephrotic ultrasound were also normal. CONCLUSIONS: We reported the first Chinese case of transient antenatal Bartter's syndrome caused by MAGED2 mutation. The 4-year follow-up of our case further demonstrates the benign prognosis of the disease and indicates that early recognition of this phenotype could avoid unnecessary treatments.

The D-dimer level predicts the prognosis in patients with lung cancer: a systematic review and meta-analysis.

OBJECTIVE: Although the significance of increased plasma D-dimer levels in activating coagulation and fibrinolysis has been reported, it is still controversial whether it can be used to predict the prognosis of lung cancer patients. This meta-analysis was performed to explore the beneficial role of plasma D-dimer as a prognostic factor in lung cancer patients according to a larger sample capacity. MATERIALS AND METHODS: MEDLINE, EMBASE, and Cochrane Central databases were searched from inception to January 2021. The data are mainly hazard ratio(HR) with 95% confidence interval (CI) and Kaplan-Meier survival curves. The publication bias was examined by Egger's test. RESULTS: Finally, a total of 28 studies, enrolling 8452 patients were included in the current meta-analysis. Our results showed that the OS (HR = 1.742, 95%CI:1.542-1.969, P < 0.001) and PFS (HR = 1.385, 95%CI:1.169-1.641, P = 0.003) in the high D-dimer group were significantly lower than those in the low D-dimer group. Subgroup analysis suggested that localization, detection methods and disease stage had an important effect on the prognosis. CONCLUSION: This meta-analysis revealed that the high plasma D-dimer level leads to lower survival than in the low D-dimer level, which might provide an important clue for high plasma D-dimer level as an independent factor of poor prognosis in patients with lung cancer.

The concept of broad exposure facilitates uniportal video-assisted thoracoscopic mediastinal lymph nodes dissection.

BACKGROUND: Systematic lymph node dissection is an important part of radical resection for lung cancer. Insufficient incision of the mediastinal pleura results in a tapered or tunnel-like operation surface, which increases the difficulty of uniportal video-assisted thoracoscopic mediastinal lymph node dissection. The objective of this study was to report our concept of broad exposure and investigate the efficacy and safety of this concept in uniportal video-assisted thoracoscopic mediastinal lymph nodes dissection. METHODS: We retrospectively analyzed the clinical data of the 204 non-small cell lung cancer patients who underwent uniportal video-assisted thoracoscopic surgery for anatomical lobectomy and systematic lymph node dissection following the concept of broad exposure. SPSS 23.0 software was used for statistical analysis. RESULTS: All operations were completed under uniportal video-assisted thoracoscopic surgery following the concept of broad exposure. The median surgery time was 102 (range, 76-285) minutes and the median blood loss was 50 (range, 20-900) milliliters. The median chest tube duration time was 2 (range, 1-6) days, the median postoperative hospital duration time was 5 (range, 4-10) days. The median number of dissected lymph node stations and dissected lymph nodes were 8 (range,6-9) and 15(range,12-19), respectively. The median number of dissected mediastinal lymph nodes stations and dissected mediastinal lymph nodes were 5(range,3-6) and 11(range,10-15), respectively. The up-staging rate of N staging was 6.86%. The postoperative complication rate was 10.29% and there was no perioperative death. CONCLUSIONS: According to our results, it's effective and safe to perform uniportal video-assisted thoracoscopic mediastinal lymph nodes dissection following the concept of broad exposure. This new concept not only emphasizes sufficient exposure, but also focuses on protection of important tissues.

Wireless Microfluidic Sensor for Metal Ion Detection in Water.

In the present work, a wireless microfluidic sensor based on low-temperature cofired ceramic (LTCC) technology for real-time detection of metal ions in water is proposed. The wireless sensor is composed of a planar spiral inductor and parallel plate capacitor (LC) resonant antenna, which integrates with the microchannel in the LTCC substrate between the capacitor plates. Aqueous solutions of Pb(NO3)2, Cd(NO3)2, Mg(NO3)2, Ca(NO3)2, NaNO3, and KNO3 with concentrations of 0-100 mM were tested with the sensors. The metal ion and its concentration in water can be tested by the amplitude of the reflection coefficient (S 11) and the resonance frequency (f r) of the wireless microfluidic sensor. The metal ion species can be distinguished from the wireless response behavior of the sensor. The detection limit of the sensor for the selected metal ionic solutions could reach as low as 5 µM. The normalized sensitivity of the sensor is 0.47%, which is higher than that of the reported liquid microfluidic sensors based on microwave resonators. The wireless microfluidic sensor of this study is promising for rapid and convenient detection of heavy metal ion pollutants in the industrial wastewater.

Structure and Microwave Dielectric Properties of Gillespite-Type ACuSi4O10 (A = Ca, Sr, Ba) Ceramics and Quantitative Prediction of the Q × f Value via Machine Learning.

Structure and dielectric properties of gillespite-type ceramics ACuSi4O10 (A = Ca, Sr, Ba) were investigated by crystal structure refinement, far-infrared reflectivity spectroscopy, and microwave dielectric measurements. A series of (CaxSr1-x)CuSi4O10 (0 < x < 1) ceramics with relative permittivities of 5.70-5.82, Q × f values of 20391-48794 GHz (@ ∼ 13.5 GHz), and τf of -46.3 to -38.9 ppm/°C were synthesized. By Ca2+ substitution for Sr2+ at the A-site, the rigid double-layered copper silicate framework remains stable, resulting in the nearly unchanged relative permittivity, while the [(Ca,Sr)O8] dodecahedron undergoes shrinkage and distortion, which is correlated to the changes in the Q × f and τf values. The normalized bond valence sums indicate that almost all ions are rattling, weakening the bond strengths and enlarging the molecular dielectric polarizability. The fitting of far-infrared reflectivity spectra reveals that the local structure changes suppress the intermediate and low-frequency vibrational modes significantly and improves the contribution from electronic polarization to permittivity. Symmetry breaking of the [(Ca,Sr)O8] dodecahedron conforms to the elevated restoring forces acting on the ions and improves the τf value. The large span in Q × f value may have intricate correlations to local structure changes and defects. Machine learning methods were introduced to explore the decisive structural factors for the Q × f value. A Q × f value prediction model correlated with the A-O2 bond length and the variance of A-O bond lengths was established. The Q × f values of isostructural (BaySr1-y)CuSi4O10 ceramics were predicted and verified by experiments.