[Clinicopathologic characteristics and prognostic analysis of testicular diffuse large B-cell lymphoma].

Objective: To analyze the clinicopathologic characteristics and prognosis of testicular diffuse large B-cell lymphoma (DLBCL) . Methods: A retrospective analysis was performed on 68 patients with testicular DLBCL admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2001 to April 2020. The gene mutation profile was evaluated by targeted sequencing (55 lymphoma-related genes) , and prognostic factors were analyzed. Results: A total of 68 patients were included, of whom 45 (66.2% ) had primary testicular DLBCL and 23 (33.8% ) had secondary testicular DLBCL. The proportion of secondary testicular DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ (P<0.001) , elevated LDH (P<0.001) , ECOG score ≥ 2 points (P=0.005) , and IPI score 3-5 points (P<0.001) is higher than that of primary testicular DLBCL patients. Sixty-two (91% ) patients received rituximab in combination with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) -based first-line regimen, whereas 54 cases (79% ) underwent orchiectomy prior to chemotherapy. Patients with secondary testicular DLBCL had a lower estimated 5-year progression-free survival (PFS) rate (16.5% vs 68.1% , P<0.001) and 5-year overall survival (OS) rate (63.4% vs 74.9% , P=0.008) than those with primary testicular DLBCL, and their complete remission rate (57% vs 91% , P=0.003) was also lower than that of primary testicular DLBCL. The ECOG scores of ≥2 (PFS: P=0.018; OS: P<0.001) , Ann Arbor stages Ⅲ-Ⅳ (PFS: P<0.001; OS: P=0.018) , increased LDH levels (PFS: P=0.015; OS: P=0.006) , and multiple extra-nodal involvements (PFS: P<0.001; OS: P=0.013) were poor prognostic factors in testicular DLBCL. Targeted sequencing data in 20 patients with testicular DLBCL showed that the mutation frequencies of ≥20% were PIM1 (12 cases, 60% ) , MYD88 (11 cases, 55% ) , CD79B (9 cases, 45% ) , CREBBP (5 cases, 25% ) , KMT2D (5 cases, 25% ) , ATM (4 cases, 20% ) , and BTG2 (4 cases, 20% ) . The frequency of mutations in KMT2D in patients with secondary testicular DLBCL was higher than that in patients with primary testicular DLBCL (66.7% vs 7.1% , P=0.014) and was associated with a lower 5-year PFS rate in patients with testicular DLBCL (P=0.019) . Conclusion: Patients with secondary testicular DLBCL had worse PFS and OS than those with primary testicular DLBCL. The ECOG scores of ≥2, Ann Arbor stages Ⅲ-Ⅳ, increased LDH levels, and multiple extra-nodal involvements were poor prognostic factors in testicular DLBCL. PIM1, MYD88, CD79B, CREBBP, KMT2D, ATM, and BTG2 were commonly mutated genes in testicular DLBCL, and the prognosis of patients with KMT2D mutations was poor.

Nonfood Probiotic, Prebiotic, and Synbiotic Use Reduces All-Cause and Cardiovascular Mortality Risk in Older Adults: A Population-Based Cohort Study.

OBJECTIVES: Pro-, pre-, and synbiotic supplements improve cardiovascular risk factors. However, the association between nonfood pro-, pre-, and synbiotics (NPPS) and long-term all-cause and cardiovascular mortality has not been studied. Thus, our objective was to determine the impact of nonfood pro-, pre-, and synbiotics on all-cause and cardiovascular mortality. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective, cohort study of 4837 nationally representative American participants aged 65 years or older with a median follow-up duration of 77 months. MEASUREMENTS: All-cause and cardiovascular mortality were measured. RESULTS: A total of 1556 participants died during the median 77-month follow-up, and 517 died from cardiovascular disease. Compared with participants without NPPS use, participants who used NPPS experienced a reduced risk of all-cause mortality by nearly 41% (hazard ratio 0.59, 95% CI 0.43 to 0.79) and cardiovascular mortality by 52% (HR 0.48, 95% CI 0.30 to 0.76). Such an effect persisted in most subgroup analyses and complete-case analyses. CONCLUSION AND RELEVANCE: In this study, we found a protective effect of NPPS against all-cause and cardiovascular mortality in Americans aged 65 years or older. Nonfood pro-, pre-, and synbiotics can be a novel, inexpensive, low-risk treatment addition for all-cause and cardiovascular mortality for older individuals.

[Development of parenting behavior scale for caregivers of children aged 2 to 6 years and analysis for its reliability and validity].

To develop a caregiver parenting behavior scale for children aged 2 to 6 years, and to verify its reliability and validity. This study recruited 1 350 caregivers of children aged 2 to 6 years. The item discrimination analysis and exploratory factor analysis were used to analyze the structure, dimensions and items of the scale. Homogeneity reliability, split-half reliability and test-retest reliability were used to analyze the reliability of the scale. Content validity and construct validity were used to analyze the validity of the scale. The results showed that the final scale contained 7 dimensions and 45 items. Cronbach's α coefficient of the total scale was 0.945; the coefficient of split half was 0.899; the test-retest reliability analysis showed that the correlation coefficients between the two tests were 0.893 (total score), 0.854 (social), 0.832 (language), 0.871 (gross motor), 0.893 (fine motor), 0.862 (cognitive), 0.832 (self-care), and 0.872 (sensory). The content validity analysis was carried out by two rounds of expert argumentation using Delphi expert consultation method. The Kendall coefficient of the items score in two rounds of Delphi expert consultation was 0.813 (P<0.01). The structure validity analysis showed that there were significant correlations between each dimension and the total scale, also between each dimension of the scale, and the extracted average variance values of each dimension was greater than the correlation coefficients between this dimension and other dimensions. In conclusion, the reliability and validity of the scale are qualified. It can be used as a tool to evaluate and guide the parenting behavior of caregivers of children aged 2 to 6 years.

[Safety analysis of cesarean myomectomy in twin pregnancies with intramural myomas].

Objective: To estimate the safety of myomectomy in twin pregnant women with intramural myomas during cesarean section. Methods: The clinical data of 145 cases of twin pregnancies with intramural myomas who were delivered by cesarean section in Beijing Obstetrics and Gynecology Hospital, Capital Medical University from June 2013 to December 2021 were collected. Maternal demographics, fibroids' characteristics, maternal and fetal outcomes were compared between groups of cesarean section with myomectomy (myomectomy group, 49 cases) and cesarean section only (non-myomectomy group, 96 cases). Results: Compared with non-myomectomy group, myomectomy group had significantly prolonged operative time [50.0 minutes (37.5-57.5 minutes) vs 40.0 minutes (35.0-50.0 minutes), respectively; P=0.007] and significantly longer postoperative hospital stay [4.0 days (3.0-4.0 days) vs 3.0 days (3.0-4.0 days), respectively; P=0.047). Other maternal and fetal outcomes such as estimated blood loss, hemoglobin difference, postpartum hemorrhage, blood transfusion, B-Lynch structure, uterine artery ligation, postoperative fever and neonatal Apgar score showed no significant differences (all P>0.05). For intramural myomas <5 cm, there were no significant differences in maternal and fetal outcomes between myomectomy group and non-myomectomy group (all P>0.05). For intramural myomas ≥5 cm, operative time [55.0 minutes (40.0-60.0 minutes) vs 42.5 minutes (40.0-50.0 minutes), respectively; P=0.019] was significantly prolonged, postoperative hospital stay [4.0 days (4.0-5.0 days) vs 4.0 days (3.0-4.0 days), respectively; P=0.048] was significantly longer in myomectomy group than non-myomectomy group, but there were no significant differences in other maternal and fetal outcomes (all P>0.05). Conclusion: For twin pregnancies with intramural myomas, it is safe and feasible to remove intramural myomas during cesarean section by experienced obstetricians.

Effects of dezocine combined with dexmedetomidine on adverse reactions and inflammatory factors in patients undergoing HIPEC after intestinal surgery and its protective effect on the heart in the perioperative period.

OBJECTIVE: The aim of this study was to explore the effects of dezocine combined with dexmedetomidine on adverse reactions and inflammatory factors in patients undergoing hyperthermic intraperitoneal chemotherapy (HIPEC) after intestinal surgery and its protective effect on the heart in the perioperative period. PATIENTS AND METHODS: A total of 80 patients treated with HIPEC after intestinal surgery in our hospital from September 2018 to December 2019 were enrolled as research subjects. All patients were evenly divided into two groups using a random number table. As to analgesia and sedation during treatment, dezocine was injected intramuscularly at 30 min before treatment in the control group. Meanwhile, dezocine combined with dexmedetomidine was given in the same way in the observation group. Adverse reactions and changes in numeric rating scale (NRS) pain score during intervention were compared between the two groups. The changes in the levels of inflammatory and myocardial injury-related factors, and vascular endothelial function and regeneration ability among cardiovascular indicators at 12 h after intervention were compared as well. Additionally, the correlations of left ventricular mass index (LVMI) with the changes in the levels of inflammatory factor high-sensitivity C-reactive protein (hs-CRP), myocardial injury-related factor lactic dehydrogenase (LDH), vascular endothelial function indicator endothelin-1 (ET-1) and cardiovascular regeneration ability index vascular endothelial growth factor (VEGF) were analyzed. RESULTS: Compared with control group, the total prevalence rate of severe pain, respiratory depression, nausea and vomiting, diarrhea, and muscle rigidity during intervention was significantly reduced in the observation group (p<0.05). NRS pain score at 1, 4, 8 and 12 h after intervention decreased remarkably in the observation group compared with the control group (p<0.05). Meanwhile, the levels of inflammatory factors tumor necrosis factor-α (TNF-α) and hs-CRP, and myocardial injury-related factors LDH and creatine kinase MB (CKMB) as well as ET-1 at 12 h after intervention declined remarkably in observation group compared with control group (p<0.05). However, the levels of nitric oxide (NO), VEGF and basic fibroblast growth factor (bFGF) rose significantly in the observation group (p<0.05). Besides, LVMI was positively correlated with hs-CRP and LDH, whereas was negatively associated with ET-1 and VEGF (p<0.05). CONCLUSIONS: In HIPEC, dezocine combined with dexmedetomidine used for sedation and analgesia is able to effectively reduce adverse reactions and relieve inflammatory responses in vivo, exerting a cardio-protective effect.

Direct estimation and correction of residual aberrations in the reconstructed exit-wavefunction of a crystalline specimen.

Measuring residual aberrations up to second order using a crystalline specimen in transmission electron microscope is challenging. Here, we show by good examples of both experimental and simulated images that it is feasible to measure aberrations up to the second-order, using minimum amplitude contrast criterion for the exit wave function reconstructed. We propose a two-steps strategy for the task: (i) Firstly measuring defocus and two-fold astigmatism simultaneously to avoid error accumulation and to reduce the number of dimensions in parameters space. (ii) Then, with minimized misleading effects (or errors) in defocus and two-fold astigmatism, estimations of three-fold astigmatism and coma can be conducted more efficiently and effectively. Influences of other factors such as specimen structure, resolution and specimen thickness on the validity of the method are also discussed in detail. Our study provides a practical procedure for correcting residual aberrations in image wave using crystalline materials, which can then facilitate application of exit wave reconstruction technique to materials research.

[Bioinformatics analysis of differently expressed genes in osteoblastic sarcoma and screening of key genes].

Objective: To screen the different expressed genes between osteosarcoma and normal osteoblasts, and find the key genes for the occurrence and development of osteosarcoma. Methods: The gene expression dataset GSE33382 of normal osteoblasts and osteosarcoma was obtained from Gene Expression Omnibus (GEO) database. The different expressed genes between normal osteoblasts and osteosarcoma were screened by limma package of R language, and the different expressed genes were analyzed by Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. The protein interaction network was constructed by the String database, and the network modules in the interaction network were screened by the molecular complex detection (MCODE) plug-in of Cytoscape software. The different expressed genes contained in the first three main modules screened by MCODE were analyzed by gene ontology (GO) using the BiNGO module of Cytoscape software. The MCC algorithm was used to screen the top 10 key genes in the protein interaction network. The gene expression and survival dataset GSE39055 of osteosarcoma was obtained from GEO database, and the survival analysis was performed by Kaplan-Meier method. The data of 48 patients with osteosarcoma treated in the First Affiliated Hospital of Fujian Medical University from January 2005 to December 2015 were selected for verification. The expression of STC2 protein in osteosarcoma was detected by immunohistochemical method, and the survival analysis was carried out combined with the clinical data of the patients. Results: A total of 874 different expressed genes were identified from GSE33382 dataset, including 402 down-regulated genes and 472 up-regulated genes. KEGG enrichment analysis showed that different expressed genes were mainly related to p53 signal pathway, glutathione metabolism, extracellular matrix receptor interaction, cell adhesion molecules, folate tolerance, and cell senescence. The top 10 key genes in the interaction network were GAS6, IL6, RCN1, MXRA8, STC2, EVA1A, PNPLA2, CYR61, SPARCL1 and FSTL3. STC2 was related to the survival rate of patients with osteosarcoma (P<0.05). The results showed that the expression of STC2 protein was related to tumor size and Enneking stage in 48 cases of osteosarcoma. The median survival time of 25 cases with STC2 high expression was 21.4 months, and that of 23 cases with STC2 low expression was 65.4 months. The survival rate of patients with high expression of STC2 was lower than that of patients with low expression of STC2 (P<0.05). Conclusions: Bioinformatics analysis can effectively screen the different expressed genes between osteosarcoma and normal osteoblasts. STC2 is one of the important predictors for the prognosis of osteosarcoma.

Potential biomarkers and lncRNA-mRNA regulatory networks in invasive growth hormone-secreting pituitary adenomas.

PURPOSE: Growth hormone-secreting pituitary adenomas (GH-PAs) are common subtypes of functional PAs. Invasive GH-PAs play a key role in restricting poor outcomes. The transcriptional changes in GH-PAs were evaluated. METHODS: In this study, the transcriptome analysis of six different GH-PA samples was performed. The functional roles, co-regulatory network, and chromosome location of differentially expressed (DE) genes in invasive GH-PAs were explored. RESULTS: Bioinformatic analysis revealed 101 DE mRNAs and 70 DE long non-coding RNAs (lncRNAs) between invasive and non-invasive GH-PAs. Functional enrichment analysis showed that epithelial cell differentiation and development pathways were suppressed in invasive GH-PAs, whereas the pathways of olfactory transduction, retinol metabolism, drug metabolism-cytochrome P450, and metabolism of xenobiotics by cytochrome P450 had an active trend. In the protein-protein interaction network, 11 main communities were characterized by cell- adhesion, -motility, and -cycle; transport process; phosphorus and hormone metabolic processes. The SGK1 gene was suggested to play a role in the invasiveness of GH-PAs. Furthermore, the up-regulated genes OR51B6, OR52E4, OR52E8, OR52E6, OR52N2, MAGEA6, MAGEC1, ST8SIA6-AS1, and the down-regulated genes GAD1-AS1 and SPINT1-AS1 were identified in the competing endogenous RNA network. The RT-qPCR results further supported the aberrant expression of those genes. Finally, the enrichment of DE genes in chromosome 11p15 and 12p13 regions were detected. CONCLUSION: Our findings provide a new perspective for studies evaluating the underlying mechanism of invasive GH-PAs.

[Differential analysis of gene expression profiles in hepatocellular carcinoma patients with high and low levels of alpha-fetoprotein].

Objective: To investigate the differential gene expression profiles of alpha-fetoprotein (AFP) high- and low-expressing hepatocellular carcinoma (HCC), and to provide a theoretical basis for the molecular mechanism and prognosis analysis of HCC. Methods: The transcriptome data and related clinical information from 368 HCC cases were obtained from the Cancer Gene Atlas (TCGA) public database. The samples were divided into AFP high expression (AFP(high)) group and low expression (AFP(low)) group according to the quartile of AFP mRNA expression, with 92 cases in each group. The differential gene analysis was carried out using the DEseq2 package in the R software. The functional and KEGG pathway enrichment analysis of the differential genes was performed using ClusterProfiler package. The protein-protein interaction network was constructed to screen hub genes using the String database and Cytoscape software. The single-sample GSEA analysis was performed to enrich and score signature gene sets using the GSVA package. And then RNAseq data and real-time quantitative polymerase chain reaction (RT-qPCR) were used for independent dataset validation and tissue validation. Results: The clinical analysis showed that high expression of AFP was significantly associated with poor pathological differentiation and ethnicity (P<0.05 for both). A total of 1 382 differential genes were obtained by bioinformatics analysis, of which 931 genes were up-regulated and 451 genes were down-regulated in AFP(high) group. GO enrichment analysis showed that the highly expressed genes were mainly correlated with the processes of appendage development, limb development, and skeletal system development, while lowly expressed genes were related to metabolic-related processes such as xenobiotic metabolism, steroid metabolism, and cellular response to xenobiotic stimuli. KEGG pathway enrichment analysis revealed that highly expressed genes were mainly involved in primary immunodeficiency, neuroactive ligand-receptor interaction, and cytokine-cytokine receptor interaction, while lowly expressed genes were mainly involved in retinol metabolism, chemical carcinogenesis, steroid hormone biosynthesis and other pathways. A prognostic related gene set that was consisted of AURKB, TTK, CENPA, UBE2C, HJURP, and KIF15 was identified. And the high expression of this gene set was related to the shorter recurrence-free survival and overall survival time in HCC patients, and its enrichment score was positively correlated with AFP expression (r=0.475, P<0.001). The validation results of RNAseq data were basically consistent with the TCGA data. The RT-qPCR results showed that AURKB, KIF15, and UBE2C were significantly overexpressed in HCC tissues with high AFP expression. Although the expression of AURKB, TTK, KIF15, and UBE2C was not related to recurrence-free survival and overall survival of HCC patients, there was a tendency that the patients with high AFP levels showed relatively shorter recurrence-free survival time and overall survival time. Conclusions: There is a large difference in gene expression profiles between AFP(high) and AFP(low) HCC. The prognostic signature may cooperate with AFP to promote the initiation and development of HCC. It also may explain the tumorigenesis in HCC with different AFP levels, and provide new clues for the prognosis of HCC.

Identification of the CD200R1 promoter and the association of its polymorphisms with the risk of Parkinson's disease.

BACKGROUND AND PURPOSE: Neuroinflammation is known to be involved in the pathogenesis of Parkinson's disease (PD). Abnormal activation of microglia plays a key role in this pathological process. CD200R1 is a membrane glycoprotein that is expressed primarily on myeloid cells including microglia and is involved in the maintenance of microglia in a stationary state. Our previous study reported that the regulation of CD200R1 expression is altered in PD patients. Such alteration will lead to neuroinflammation and is related to the pathogenesis of PD. The possible role of promoter polymorphisms for abnormal CD200R1 expression in PD was examined in this study. METHOD: The UCSC database and dual-luciferase assays were used to confirm the promoter region of CD200R1. The promoter of CD200R1 was sequenced in 457 PD patients and 520 matched healthy controls from the Chinese Han population. Dual-luciferase assays were conducted to examine the promoter activity of CD200R1. RESULTS: It was confirmed that the promoter of CD200R1 is located in the region 876-146 bp upstream of the coding DNA sequence. The frequencies of rs144721913 (P = 0.001) and rs72952157 (P = 0.022) in the promoter were significantly different between the PD group and control group. rs144721913 increases the risk of PD by approximately 14-fold and rs72952157 by 2.6-fold. The dual-luciferase assay indicated that the rs144721913 T allele and the rs72952157 G allele reduced the transcriptional activity of the CD200R1 promoter. CONCLUSIONS: For the first time the promoter region of CD200R1 has been defined and two potential risk polymorphisms (rs144721913 and rs72952157) in the region for PD in Chinese Han populations have been reported.

[Feasibility and safety of magnetically guided capsule endoscopy in minors].

Objective: To clarify the feasibility and safety of magnetically guided capsule endoscopy (MGCE) in minors. Methods: A descriptive cohort study was carried out to retrospectively collect the data of minors (<18 years) who underwent MGCE in Ruijin Hospital from April 2015 to October 2018. Exclusion criteria: patients with dysphagia, obvious gastrointestinal bleeding, diagnosed or suspected gastrointestinal obstruction, or congenital gastrointestinal malformations or intestinal fistula; patients with previous bowel surgery, or in poor general condition; patients with implants; pregnant patients; patients with incomplete data or without data. A total of 218 patients, including 122 males and 96 females, with mean age of (12.0±3.1) (5-17) years and 236 times of examination were included. The capsule size of the Ankon MGCE system was 11.8 mm×27 mm, taking two pictures per second, with a viewing angle of 140 degrees. Data of gastric visualization (0% to 100%), gastric cleanliness (satisfactory cleanliness was defined as a clear display of the gastric mucosa; the effect of bubbles or mucus on the visual field was negligible, or the gastric mucosa was slightly blurred; a small amount of air bubbles or mucus affected slightly the field of view), gastric or small bowel examination time, lesion detection rate, etc. were recorded. All the patients were followed up for 2 weeks to confirm capsule excretion and to record adverse events. Results: A total of 202 patients (217 times) completed gastric examination and 112 patients (125 times) completed small bowel examination. The median gastric visualization of cardia, fundus, body, angulus, antrum and pylorus was 100%, 90% (75%,100%), 100% (80%,100%), 100%, 100%, and 100%, respectively. The cleanliness of the gastric cardia, fundus, body, angle, antrum, and pylorus was assessed to be satisfactory in 100.0%, 76.5% (153/200), 92.5% (185/200), 97.5% (195/200), 99.5% (199/200), and 100.0% of patients, respectively. In 202 patients undergoing gastric examination, the median gastric exanimation time was 10.5 (7.3, 13.9) minutes. In 112 patients undergoing small bowel examination, the median gastric transit time was 51.5 (20.6, 112.0) minutes and the median small bowel transit time was 232.4 (181.8, 321.6) minutes. The small bowel transit rate was 91.1% (102/112). The lesion detection rates of stomach, duodenum and jejunoileum were 18.8% (38/202), 8.1% (10/124) and 26.8% (30/112) respectively. No complications or adverse events occurred. Conclusion: MGCE is feasible and safe to detect both gastric cavity and small bowel in minors.

Feasible atomic-resolution electron tomography for general crystal surfaces by quantitative reconstruction from a high-resolution image.

Whether or not the 3-dimensional surface morphologies of a crystal sample can be reconstructed at atomic-scale from a single 2-dimensional image becomes an interesting issue in high-resolution transmission electron microscopy, after the work by Jia et al. [1]. Here we propose an improved and self-validated algorithm to enhance such an electron tomography method and to make it applicable to more general crystal surfaces even with thin amorphous layers. Our study shows that a resolution in the beam (z) direction and a confidence level have to be defined and estimated after performing tomographic reconstruction in order to evaluate the quality and the reliability of its result. Applying the proposed procedure to the Si[110] image to recover the surface morphologies of a silicon crystal with amorphous contamination, the obtained results show that an atomic-resolution of 0.384 nm in the z-direction and a high confidence level of 95% are achieved for imaging the Si-surface structures, quantitatively described by tomographic parameters, i.e., the height (defocus) and the thickness (atom number) of Si-atomic columns.

Pharmacological Signatures of the Exenatide Nanoparticles Against Hepatic Ischemia/Reperfusion-induced Pancreatic Injury.

BACKGROUND: Hepatic ischemia/reperfusion-induced pancreatic injury (HI/RPI) is an important pathophysiological phenomenon in clinics. Exenatide is found to have hepatopancreatic protection; however, the half-life of exenatide is extremely short, which limits its clinical application. In the present study, we described an exenatide nanocarrier based on poly(L-lysine)-poly(ethylene glycol)-poly(L-lysine) (PLL-PEG-PLL) and aimed to investigate the protective effects of exenatide/PLL-PEG-PLL on HI/RPI. METHODS: PLL-PEG-PLL was synthesized and estimated by being applied as a nanocarrier for lengthening delivery of exenatide. Exenatide was loaded into PLL-PEG-PLL by electrostatic interactions at pH 7.4. The loading and release of exenatide from PLL-PEG-PLL were characterized in vitro. The pancreatic protection of exenatide/PLL-PEG-PLL was assessed using the animal model, histopathological examination, blood biochemical indices detection, antioxidant activity, and anti-inflammatory evaluation in vivo. RESULTS: Exenatide/PLL-PEG-PLL displayed efficient loading and sustained release. Exenatide/PLL-PEG-PLL complex moderated HI/RPI and enlarged islet functionality compared to free exenatide. CONCLUSION: We propose that the nanocarrier PLL-PEG-PLL may function as a potent exenatide nanocarrier for augmenting anti-HI/RPI pharmacotherapy with unprecedented clinical benefits.

Ultra-deep next-generation sequencing of plasma cell-free DNA in patients with advanced lung cancers: results from the Actionable Genome Consortium.

BACKGROUND: Noninvasive genotyping using plasma cell-free DNA (cfDNA) has the potential to obviate the need for some invasive biopsies in cancer patients while also elucidating disease heterogeneity. We sought to develop an ultra-deep plasma next-generation sequencing (NGS) assay for patients with non-small-cell lung cancers (NSCLC) that could detect targetable oncogenic drivers and resistance mutations in patients where tissue biopsy failed to identify an actionable alteration. PATIENTS AND METHODS: Plasma was prospectively collected from patients with advanced, progressive NSCLC. We carried out ultra-deep NGS using cfDNA extracted from plasma and matched white blood cells using a hybrid capture panel covering 37 lung cancer-related genes sequenced to 50 000× raw target coverage filtering somatic mutations attributable to clonal hematopoiesis. Clinical sensitivity and specificity for plasma detection of known oncogenic drivers were calculated and compared with tissue genotyping results. Orthogonal ddPCR validation was carried out in a subset of cases. RESULTS: In 127 assessable patients, plasma NGS detected driver mutations with variant allele fractions ranging from 0.14% to 52%. Plasma ddPCR for EGFR or KRAS mutations revealed findings nearly identical to those of plasma NGS in 21 of 22 patients, with high concordance of variant allele fraction (r = 0.98). Blinded to tissue genotype, plasma NGS sensitivity for de novo plasma detection of known oncogenic drivers was 75% (68/91). Specificity of plasma NGS in those who were driver-negative by tissue NGS was 100% (19/19). In 17 patients with tumor tissue deemed insufficient for genotyping, plasma NGS identified four KRAS mutations. In 23 EGFR mutant cases with acquired resistance to targeted therapy, plasma NGS detected potential resistance mechanisms, including EGFR T790M and C797S mutations and ERBB2 amplification. CONCLUSIONS: Ultra-deep plasma NGS with clonal hematopoiesis filtering resulted in de novo detection of targetable oncogenic drivers and resistance mechanisms in patients with NSCLC, including when tissue biopsy was inadequate for genotyping.

[Tear film stability after trabeculectomy and its relationship with bleb morphology].

Objective: To investigate the tear film stability after trabeculectomy and its relationship with bleb morphology using Optical Quality Analysis System Ⅱ (OQAS Ⅱ). Methods: A cross-sectional study. Glaucoma patients undergoing trabeculectomy in the Eye Hospital of Wenzhou Medical University from November 2011 to November 2016 were invited by telephone to perform optical quality, bleb photography, and break-up time examinations, and history of surgeries and medications was collected. Bleb morphology was graded according to the Indiana bleb appearance grading scale. The tear film stability was the average objective scatter index value measured using OQAS Ⅱ for 10 seconds after blinking minus the baseline objective scatter index. The higher the tear film stability value, the worse the stability. The difference in the tear film stability between the surgical eyes and non-surgical eyes was compared by the Mann-Whitney U test, and the relationships between the optical quality, bleb height, extent and vascularity were compared by the Kruskal-Wallis H test. Results: Sixty-three patients (76 eyes) were enrolled in the study, including 55 surgical eyes and 21 non-surgical eyes. The mean follow-up time was (39.6±26.2) months.In the surgical and non-surgical eyes, the M(Q(R)) of tear film stability was 0.46 (0.86) and 0.23 (0.41), respectively. The tear film stability in the surgical eyes was reduced compared to the non-surgical eyes (P=0.044). The trabeculectomy group was divided into three subgroups according to the height of the filtering bleb: H0 (17 eyes), H1 (24 eyes) and H2-3 (14 eyes). The M(Q(R)) of tear film stability in the three subgroups was 0.40(0.68), 0.70(1.02) and 0.40(1.24), respectively, with no statistically significant difference detected (P=0.481). According to the bleb extent, the surgical group was divided into two subgroups: E0-1 (36 eyes) and E2-3 (19 eyes). The M(Q(R)) of optical quality in the two subgroups was 0.63 (0.78) and 0.26(1.17), respectively, with no significant difference detected (P=0.261). According to the degree of bleb vascularity, the surgical group was divided into three subgroups: V0 (25 eyes), V1 (14 eyes), and V2-3 (16 eyes). The M(Q(R)) of optical quality in the three subgroups was 0.39 (0.69), 0.55 (1.18) and 0.63 (1.24), respectively, with no significant difference (P=0.401). Conclusion: Although tear film stability decrease after trabeculectomy, the decrease is not associated with the bleb morphology. (Chin J Ophthalmol, 2019, 55:214-219).

Quantum Oscillations of the Positive Longitudinal Magnetoconductivity: A Fingerprint for Identifying Weyl Semimetals.

Weyl semimetals (WSMs) host charged Weyl fermions as emergent quasiparticles. We develop a unified analytical theory for the anomalous positive longitudinal magnetoconductivity (LMC) in a WSM, which bridges the gap between the classical and ultraquantum approaches. More interestingly, the LMC is found to exhibit periodic-in-1/B quantum oscillations, originating from the oscillations of the nonequilibrium chiral chemical potential. The quantum oscillations, superposed on the positive LMC, are a remarkable fingerprint of a WSM phase with a chiral anomaly, whose observation is a valid criteria for identifying a WSM material. In fact, such quantum oscillations were already observed by several experiments.

Magnetic resonance spectroscopy may serve as a presurgical predictor of somatostatin analog therapy response in patients with growth hormone-secreting pituitary macroadenomas.

PURPOSE: Somatostatin analogs (SSAs) are considered one of the most effective medical treatments for patients with growth hormone-secreting pituitary adenomas (GH-PAs). The postoperative electron microscopy (EM) pathological subtype and SSTR2 expression in the tumor are the most established predictors of patient response to SSA therapy. The aim of this study was to evaluate how will magnetic resonance spectroscopy (MRS) measurements before surgery predict the EM pathological subtypes and SSTR2 expression of tumors, and thereby serve as an indicator for the therapeutic sensitivity to SSAs of patients with GH-PAs. METHODS: Eighteen patients with GH pituitary macroadenomas who underwent transsphenoidal surgery were included in this retrospective study. The preoperative MRS data and T2 signal intensity were obtained from patients by 1.5 T MR spectroscopy of the sellar mass. The EM pathological subtypes of tumors were determined after surgery through examination of cell granulations. The expressions of somatostatin receptor 2 (SSTR2), SSTR5, P21, P27, and Ki-67 were evaluated by immunohistochemistry. RESULTS: The MRS parameters that were found to significantly predict the EM pathological subtypes of tumors, as calculated by the receiver operating characteristic curve, were the choline (Ch) value at 3140.5 MR units (sensitivity 69.2%, specificity 100%) and the choline/creatine (Ch/Cr) ratio at 1.27 (sensitivity 92.3%, specificity 100%). Further, the Ch/Cr ratio, but not other MRS data, was shown to negatively correlate with the expression of SSTR2 (P = 0.02). The Ch/Cr ratio was also found to positively correlate with the Ki-67 value (P < 0.05) and T2 signal (P < 0.05), but not with other factors that were examined in this study. Moreover, the Ch/Cr ratio could predict the EM pathological subtypes of tumors with an accuracy of 83.3% (5/6) for patients with an isointense T2 signal. CONCLUSION: The Ch/Cr ratio by MRS could effectively predict the tumor subtype and was significantly correlated with the expression of SSTR2, which was consistent with other predictors. It was also able to distinguish the patients with isointense T2 signals. Our results provide a potentially new and non-invasive method to predict the response to SSAs in patients with GH pituitary macroadenomas.

[Comparisons of clinical characteristics and prognosis between patients with primary and secondary thyroid lymphoma].

Objective: To compare clinical characteristics and prognosis between patients with primary (PTL) and secondary thyroid lymphoma (STL) . Methods: A retrospective analysis was performed on 46 patients with thyroid lymphoma (PTL 19, STL 27) from January 2002 to October 2018. Results: ①PTL group included 4 males and 15 females, with a median age of 57 years. The STL group included 10 males and 17 females, with a median age of 61 years. Diffuse large B-cell lymphoma (DLBCL) was the main pathological subtype in both PTL and STL groups, with 14 cases (73.7%) and 20 cases (74.1%) respectively. In terms of clinical manifestations, goiter was the most common symptom in PTL patients 100.0% (19/19) , while 29.6% (8/27) STL had goiter (P<0.001) . The incidences of increased thyroglobulin antibody (TRAb) /thyroid peroxidase antibody (TPO) were 81.3% (13/16) in PTL group and 43.8% (7/16) in STL group (P=0.028) respectively. Concerning the clinical features of patients, only two PTL patients (10.5%) with advanced Ann Arbor stage (Ⅲ/Ⅳ) , while 21 (77.8%) STL experienced advanced Ann Arbor stage (P<0.001) . Elevated serum ß(2)-MG were appeared in 1 (7.1%) PTL and 9 (47.4%) STL patients (P=0.013) , and advanced IPI score (3-5) was more common in STL than PTL (59.3% vs 5.3%, P<0.001) . ②Among the 17 PTL patients who received treatments, 15 (88.2%) achieved remission; as for STL patients received treatments, 23/25 (92.0%) were in remission. The 5-year overall survival (OS) rates of PTL (n=17) and STL groups (n=25) were (87.4±8.4) % and (70.0±13.1) % (P=0.433) respectively. ③The 5-year OS rate in 41 patients with B-cell thyroid lymphoma was (81.1±7.5) %. Univariate analysis showed that IPI score of 3-5 (P=0.040) and high level of serum IL-8 (P=0.022) were significantly associated with poor outcome. Conclusion: DLBCL was the most common subtype in both PTL and STL, and goiter was the major symptom in PTL. IPI score of 3-5 and high level of serum IL-8 were unfavorable prognostic factors for patients with B-cell thyroid lymphoma.

[Epidemiologic survey on the prevalence and distribution of infants' common gastrointestinal symptoms in 7 cities in China: a population-based study].

Objective: Regurgitation, infantile colic, and functional constipation are common gastrointestinal symptoms in childhood, the aim of this study was to explore the prevalence and distribution of these symptoms in China. Methods: A screening program in infants aged 0 to 3 years selected through stratified cluster random sampling was carried out in 7 cities in China. Questionnaires were filled, and then diagnosis were made according to Rome Ⅳ criteria. Areas, (urban-rural), age and gender distribution of prevalence of childhood common gastrointestinal symptoms were analyzed. Results: Totally, 20 932 effective questionnaires were returned. The total number of infants aged 0 to 1 years was 10 193. Regurgitation was diagnosed in 1 960 infants, with the prevalence of 19.2%, among infants aged 0 to 3 months that had highest prevalence (29.8%). The prevalence decreased with age, and differences among different age groups showed significant. For infantile colic, 4 470 infants aged 0 to 5 months were analyzed and the prevalence of infantile colic was 7.3%. The prevalence of infantile colic was the highest in infants aged 1 to 2 months (10.0%). Age specific difference was significant. Of all the infants, functional constipation was diagnosed in 1 755 infants with the prevalence of 8.4%, and the lowest prevalence was found in infants aged 0 to 3 months (6.2%), and the highest prevalence was in infants aged 30 to 36 months (10.0%). The differences in different age group were significant. Conclusion: Symptoms of regurgitation, infantile colic, and functional constipation are common in infants in China, with age specific difference in prevalence of the symptoms.