Identification of RET fusions in a Chinese multicancer retrospective analysis by next-generation sequencing.

Fusion of RET with different partner genes has been detected in papillary thyroid, lung, colorectal, pancreatic, and breast cancer. Approval of selpercatinib for treatment of lung and thyroid cancer with RET gene mutations or fusions calls for studies to explore RET fusion partners and their eligibility for RET-based targeted therapy. In this study, RET fusion patterns in a large group of Chinese cancer patients covering several cancer types were identified using next-generation sequencing. A total of 44 fusion patterns were identified in the study cohort with KIF5B, CCDC6, and ERC1 being the most common RET fusion partners. Notably, 17 novel fusions were first reported in this study. Prevalence of functional RET fusions was 1.05% in lung cancer, 6.03% in thyroid cancer, 0.39% in colorectal cancer, and less than 0.1% in gastric cancer and hepatocellular carcinoma. Analysis showed a preference for fusion partners in different tumor types, with KIF5B being the common type in lung cancer, CCDC6 in thyroid cancer, and NCOA4 in colorectal cancer. Co-occurrence of EGFR mutations and RET fusions with rare partner genes (rather than KIF5B) in lung cancer patients was correlated with epidermal growth factor receptor-tyrosine kinase inhibitor resistance and could predict response to targeted therapies. Findings from this study provide a guide to clinicians in determining tumors with specific fusion patterns as candidates for RET targeted therapies.

Generation of mWasabi fluorescent protein-binding nanobodies.

mWasabi is a bright monomeric green fluorescent protein. It can be used as a fusion tag to monitor various biological events, e.g. protein localization. Here we report the selection of camelid-derived single-domain antibody fragments (nanobodies) against mWasabi. In this work, phage-display approach was employed to select the high affinity mWasabi-specific Nb (nanobodies). These nanobodies were able to recognize mWasabi or in a fused fashion with PD1. The interesting binding characteristics of these two mWasabi-specific nanobodies could be valuable for design new tools for cellular tracing or targeting based on the mWasabi-fusing protein in many different biological research fields.

Nanobody against PDL1.

Programmed death ligand 1 (PDL1, CD274, B7-H1) has been identified as the ligand for the immune inhibitory receptor programmed death 1 protein (PD1/PDCD1). PDL1 is a member of B7 family of immune molecules and this protein together with PDL2, are two ligands for PD1 expressed on activated lymphoid cells. By binding to PD1 on activated T cells, PDL1 may inhibit T cell responses by inducing apoptosis. Accordingly, it leads to the immune evasion of cancers and contribute to tumor growth, thus PDL1 is regarded as therapeutic target for malignant cancers. We selected PDL1 specific nanobodies from a high quality dromedary camel immune library by phage display technology, three anti-PDL1-VHHs were developed.

Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 promotes lung adenocarcinoma by directly interacting with specificity protein 1.

Metastasis-associated lung adenocarcinoma transcript 1 (malat1) is an oncogenic long non-coding RNA (lncRNA) which has been proven to be associated with various types of tumors. Transcription factor specificity protein 1 (SP1) is overexpressed in many types of cancers. Previously, we observed that malat1 expression level is regulated by SP1 in lung cancer. In the present study, we found that transfection of expression construct of malat1 5' end fragment M5 enhances stability and transcriptional activity of SP1. Various SP1 target genes are also upregulated following overexpression of malat1 M5 in lung adenocarcinoma cells. We also showed that malat1 M5 interacts with the C-terminal domain of SP1 by RNA immunoprecipitation (RIP) assay coupled with UV cross-linking. Malat1-SP1 association results in increase of SP1 stability. In turn, SP1 promotes malat1 transcription, thus forming a positive feedback loop. In conclusion, our data show that in lung adenocarcinoma cells, malat1 interacts with SP1 protein and promotes SP1-mediated transcriptional regulation of SP1 target genes.

Diffuse parenchymal pulmonary amyloidosis associated with multiple myeloma: a case report and systematic review of the literature.

BACKGROUND: Pulmonary is an uncommon site of extramedullary involvement in multiple myeloma (MM). Diffuse parenchymal amyloidosis as pulmonary manifestation of MM is even rarer. We report a rare case of diffuse parenchymal pulmonary amyloidosis associated with MM diagnosed by video-assisted thoracoscopic lung biopsy (VATLB). CASE PRESENTATION: A 58-year-old woman complained of cough and shortness of breath. HRCT disclosed diffuse ground-glass opacifications with interlobular septal thickening in bilateral lungs. A lung-biopsy sample obtained by VATLB revealed Congo Red-positive amorphous eosinophilic deposits in the alveolar septa. Surgical biopsy of abdominal wall skin and subcutaneous fat was also performed, which showed the apple-green birefringence with polarized light on Congo red stain was demonstrated in dermis. The serum immunoelectrophoresis showed monoclonal lambda light chains. A bone marrow biopsy specimen comprised 11.5% plasma cells. She was therefore diagnosed with diffuse parenchymal pulmonary amyloidosis accompanied by MM. The patient was referred to the hematology department for further chemotherapy. CONCLUSIONS: It is important to recognize diffuse parenchymal pulmonary amyloidosis to avoid misdiagnosis.

Identification of novel driver mutations of the discoidin domain receptor 2 (DDR2) gene in squamous cell lung cancer of Chinese patients.

BACKGROUND: Although many of the recently approved genomically targeted therapies have improved outcomes for patients in non-small-cell lung cancer (NSCLC) with lung adenocarcinoma, little is known about the genomic alterations that drive lung squamous cell cancer (SCC) and development of effective targeted therapies in lung SCC is a promising area to be further investigated. Discoidin domain receptor 2 (DDR2), is a novel receptor tyrosine kinases that respond to several collagens and involved in tissue repair, primary and metastatic cancer progression. METHODS: Expression of DDR2 mRNA was analyzed in 54 lung SCC tissues by qRT-PCR. Over-expression approaches were used to investigate the biological functions of DDR2 and its' mutations in lung SCC cells. Conventional Sanger sequencing was used to investigate the mutations of DDR2 gene in 86 samples. The effect of DDR2 and its' mutations on proliferation was evaluated by MTT and colony formation assays; cell migration and invasion was evaluated by trasnwell assays. Lung SCC cells stably transfected with pEGFP-DDR2 WT, pEGFP-DDR2-S131C or empty vector were injection into nude mice to study the effect of DDR2 and its' mutation on tumorigenesis in vivo. Protein and mRNA expression levels of E-cadherin and MMP2 were determined by qRT-PCR and western blot analysis. Differences between groups were tested for significance using Student's t-test (two-tailed). RESULTS: In this study, we found that DDR2 mRNA levels were significantly decreased in 54 lung SCC tissues compared with normal lung tissues. Moreover, there were 3 novel DDR2 mutations (G531V, S131C, T681I) in 4 patients and provide the mutation rate of 4.6% in the 86 patients with lung SCC. The mutation of S131C in DDR2 could promote lung SCC cells proliferation, migration and invasion via inducing MMP-2, but reducing E-cadherin expression. CONCLUSIONS: These data indicated that the novel DDR2 mutation may contribute to the development and progression of lung SCC and this effect may be associated with increased proliferation and invasiveness, at least in part, via regulating E-cadherin expression.

Recent Advances in the Health Benefits and Application of Tangerine Peel (Citri Reticulatae Pericarpium): A Review.

Citrus fruits, renowned for their abundant of phytochemicals and bioactive compounds, hold a prominent position as commercially grown fruits with health-promoting properties. In this context, tangerine peel (Citri Reticulatae Pericarpium, CRP) is garnering attention as a byproduct of citrus fruits. Within the framework of the circular economy, CRP has emerged as a focal point due to its potential health benefits. CRP, extracted from Citrus reticulata cv. and aged for over three years, has attracted increasing attention for its diverse health-promoting effects, including its anticancer, cardiovascular-protecting, gastrointestinal-modulating, antioxidant, anti-inflammatory, and neuroprotective properties. Moreover, CRP positively impacts skeletal health and various physiological functions. This review delves into the therapeutic effects and molecular mechanisms of CRP. The substantial therapeutic potential of CRP highlights the need for further research into its applications in both food and medicine. As a value-added functional ingredient, CRP and its constituents are extensively utilized in the development of food and health supplements, such as teas, porridges, and traditional medicinal formulations.

Recent Advances in the Distribution, Chemical Composition, Health Benefits, and Application of the Fruit of Siraitia grosvenorii.

The fruits of Siraitia grosvenorii (S. grosvenorii) have attracted a lot of scientific interest as part of the current healthy diet. S. grosvenorii has diverse health-promoting effects, including antioxidant, anti-inflammatory, antimicrobial, respiratory modulation, metabolic modulation, antitumor, and neuroprotective effects, as well as gastrointestinal function modulation. As a plant resource, S. grosvenorii has broad application prospects, which promotes the development of the horticultural industry. Moreover, Mogroside has attracted much attention as an important active ingredient of S. grosvenorii. This review provides an in-depth exploration of the distribution, chemical composition, health benefits, and application of S. grosvenorii, particularly Mogroside. This comprehensive exploration highlights the important therapeutic potential of S. grosvenorii, prompting further research into its applications. As value-added functional ingredients, S. grosvenorii and its constituents have significant potential for disease prevention and are widely used in the development of food and health supplements.

Ultrasound-Guided Rhomboid Block versus Paravertebral Block in Postoperative Analgesia for Video-Assisted Thoracoscopic Surgery: A Prospective Randomized Controlled Clinical Trial.

Introduction: The anesthetic efficacy of the ultrasound-guided rhomboid intercostal block (RIB) in alleviating postoperative pain has been well concerned. This study aims to compare the effectiveness between ultrasound-guided RIB and paravertebral block (PVB) in alleviating acute pain following video-assisted thoracic surgery. Methods: It was a prospective, randomized, double-blinded clinical trial involving 132 patients with video-assisted thoracic surgery divided into three groups: the general anesthesia (GA) group, RIB group, and PVB group on T5 vertebra, using 0.4% ropivacaine at 3 mg/kg, registered in the Chinese Clinical Trial Registry (ChiCTR2100054057, "https://www.chictr.org.cn"). The visual analogue scale (VAS) scores at rest and cough during 48 h postoperatively and the postoperative consumption of pain rescue were the primary outcomes, and the QoR15 score 48 h postoperatively, the usage of opioids during and after operation, and nerve block-related complications were the secondary outcomes. Demographic characteristics, surgery characteristics, and primary outcomes between the groups were compared. Results: A total of 120 eligible patients were recruited, including 40 in each group. Baseline and surgery characteristics between the groups were comparable (all p > 0.05). The PVB and RIB groups were better than the GA group in the primary and secondary outcomes (p < 0.05). The static VAS score, QoR15 score, and block-related complications within 48 hours after surgery were better in the RIB group than in the PVB group (p < 0.001). Conclusion: Both PVB and RIB can provide adequate analgesia and accelerate the recovery of patients. Compared with PVB, RIB has a better analgesic effect, especially to avoid paravertebral pain caused by block, and the operation of RIB is more straightforward and the safety is higher.

Ultrasound-guided serratus anterior plane block versus paravertebral block on postoperation analgesia and safety following the video-assisted thoracic surgery: A prospective, randomized, double-blinded non-inferiority clinical trial.

BACKGROUND: Both the anesthetic efficacy of ultrasound-guided serrate anterior plane block (SAPB) and the ultrasound-guided paravertebral block (PVB) in alleviating postoperative pain have been well concerned. This study primarily aims to evaluate whether the ultrasound-guided SAPB and ultrasound-guided PVB can provide comparable analgesia for video-assisted thoracic surgery. Secondarily, the safety and clinical satisfaction of the two blocks are evaluated. METHODS: It was a prospective, randomized, double-blinded non-inferiority clinical trial involving 99 patients with lung nodules receiving video-assisted thoracic surgery with ultrasound-guided SAPB or PVB on T4 and T7 vertebra using 0.375% ropivacaine at 3 mg/kg. The Visual Analogue Scale (VAS) scores at rest and cough at 24 h/48 h postoperatively and the incidence and severity of chronic pain at 3 and 6 months postoperatively were the primary outcome. Secondary outcomes included the complications and block application time of two kinds of blocks, and consumption of sufentanil as an analgesic rescue. RESULTS: A total of 92 eligible patients were recruited, including 46 in the SAPB group and 46 in the PVB group. No significant differences in VAS scores at rest and cough at first 48 h, 3 months, and 6 months postoperatively between the SAPB group and PVB group were detected (all P > 0.05). The SAPB group had fewer complications and higher patient satisfaction(P＜0.05). CONCLUSION: The ultrasound-guided SAPB was not inferior to PVB in alleviating postoperative pain following the VATS with fewer complications and higher patient satisfaction.

FHL1 Overexpression as A Inhibitor of Lung Cancer Cell Invasion via Increasing RhoGDIß mRNA Expression.

Objective: Four and a half Lin-11, Isl-1, Mac-3 (LIM) protein 1 (FHL1) is one of the FHL protein family, which is regarded as a tumor suppressor in the multiple malignant tumors. In this study, we aimed to explore the regulatory effects and mechanisms of FHL1 on lung cancer cell invasion. Materials and Methods: In this experimental study, bioinformatics analysis of FHL1 transcripts in human lung adenocarcinomas of TCGA database was performed. Quantitative real-time polymerase chain reaction (PCR) was performed to detect FHL1 mRNA expression in 15 paired human lung cancer tissues and their adjacent normal lung tissues, or lung cancer cell lines (A549 and H1299) in comparison with human bronchial epithelial cell line (Beas- 2B). Moreover, western blot was used to analyze FHL1 and rho GDP-dissociation inhibitor beta (RhoGDIß) protein expression in the indicated cell lines. Also, transwell assays were employed to measure the migrated, and invaded of indicated cell lines. Results: FHL1 transcripts were downregulated in the human lung adenocarcinoma. The impaired FHL1 transcripts were positively correlated with advanced tumor node metastasis (TNM) stage. Moreover, as compared to the adjacent normal lung tissues, FHL1 mRNA was low expressed in 15 paired human lung cancer tissues than their adjacent normal lung tissues. Besides, FHL1 mRNA and protein expression were also reduced in H1299 and A549 cell lines in comparison with Beas-2B cell line. Overexpressed FHL1 protein inhibited the invasive ability of H1299 and A549 cell lines. Mechanically, FHL1 protein overexpression increased the RhoGDIß protein and mRNA abundance, while knockdown of RhoGDIß protein, completely restored the invasion ability of A549 (Flag-FHL1) cell line. Conclusion: Our findings indicated that as a key FHL1 downstream regulator, RhoGDIß is in charge of FHL1 inhibiting lung cancer cell invasion abilities, providing a critical insight into understanding the role of FHL1 for lung cancer development.

MALAT1 modulated FOXP3 ubiquitination then affected GINS1 transcription and drived NSCLC proliferation.

An increasing number of studies have shown that long-noncoding RNAs (lncRNAs) are involved in the post-translational modifications (PTMs) of protein in a variety of tumors. However, little is known about the exact regulation mechanism of lncRNAs in regulating PTMs in non-small-cell lung carcinoma (NSCLC) proliferation. Metastasis-associated lung adenocarcinoma transcript1 (MALAT1) and GINS complex subunit 1(GINS1) both were upregulated and promoted proliferation progression in NSCLC. In this study, the clinicopathologic significance of MALAT1 and GINS1 in NSCLC was investigated, a positive correlation in their expression was found. The silencing of MALAT1 decreased GINS1 expression and inhibited NSCLC proliferation in vitro and in vivo. The upregulation of GINS1 reversed NSCLC proliferation inhibited by MALAT1 knockdown. FOXP3 (forkhead box protein 3) was identified as the critical transcription factor for GINS1 transcription. In addition, MALAT1 could stabilize FOXP3 by binding to zinc finger (ZF) domain and leucine zipper (LZ) domain of FOXP3. Interestingly, these two domains were also interaction domains for FOXP3 binding with E3 ligase STUB1 (STIP1 homology and U-box containing protein 1). In this way, MALAT1 masked the protein-interacting domain, and inhibited FOXP3 ubiquitination by STUB1. Together, our results identified a novel regulatory axis of MALAT1-FOXP3-GINS1, and demonstrated that MALAT1 played an important modulatory role in PTM of FOXP3 which affects GINS1 transcription and drives proliferation character in NSCLC.

Novel MET exon 14 skipping analogs characterized in non-small cell lung cancer patients: A case study.

MET exon 14 skipping (METex14) is a validated oncogenic driver in lung cancer and MET tyrosine kinase inhibitors are now available as effective clinical treatments. The majority of known METex14 alterations are typical donor/acceptor splicing or ubiquitination site mutations. Herein, two new METex14 variants were detected in two patients with lung adenocarcinoma by targeted next generation sequencing (NGS). Reverse transcription (RT)-based analysis confirmed that these mutations led to MET exon 14 skipping. Our analysis provided evidence for possible targeted therapy options for patients carrying these MET mutations or similar METex14 analogs.

Five-lncRNA signature in plasma exosomes serves as diagnostic biomarker for esophageal squamous cell carcinoma.

Changes in expression of long non-coding RNAs (lncRNAs) in plasma exosomes can be useful for diagnosis of cancer patients. Here, we conducted a four-stage study to identify plasma exosome lncRNAs with diagnostic potential in esophageal squamous cell carcinoma (ESCC). First, plasma exosome lncRNA expression profiles were examined in ESCC patients, esophagitis patients, and healthy controls using RNA sequencing. Differentially expressed plasma exosome lncRNAs from the lncRNA expression profile were then evaluated by qRT-PCR in a large cohort of ESCC patients, esophagitis patients, and healthy controls. Expression levels of the lncRNAs NR_039819, NR_036133, NR_003353, ENST00000442416.1, and ENST00000416100.1 were significantly higher in exosomes from ESCC patients than non-cancer controls. We also confirmed that levels of these five plasma exosome lncRNAs decreased markedly in ESCC patients after surgery. Our results suggest that these five exosome lncRNAs may serve as highly effective, noninvasive biomarkers for ESCC diagnosis.

Bioinformatics analysis to determine the prognostic value and prospective pathway signaling of miR-126 in non-small cell lung cancer.

BACKGROUND: MicroRNAs (miRNAs) have been demonstrated to play crucial roles in the initiation and development of non-small cell lung cancer (NSCLC). However, further investigation of the specific role of miR-126 in NSCLC is still required. METHODS: An analysis of miR-126 expression in NSCLC was carried out using the Gene Expression Omnibus (GEO) database, and a literature review was also performed. The differentially expressed genes (DEGs) in three mRNA datasets, GSE18842, GSE19804, and GSE101929, from GEO were identified. Following the prediction of hsa-miR-126-5p target genes by TargetScan, the overlap of miR-126 target genes with DEGs in NSCLC was examined. After that, Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed. Finally, an analysis to identify the impact of hub genes on the prognosis of NSCLC was carried out on the basis of a protein-protein interaction (PPI) network constructed using STRING and Cytoscape. RESULTS: The data in the literature review revealed a trend that miR126 was downregulated in NSCLC. The number of both NSCLC-related and miR-126-related DEGs was 187. Dozens of DEGs were significantly enriched in biological regulation, cell membrane binding, and signal receptor binding. In the PPI network analysis, 3 of 10 identified hub genes, namely NCAPG, MELK, and KIAA0101, were obviously related to poor prognosis in NSCLC; the survival rate was low among patients with high expression levels of these genes. Furthermore, through network analysis, TPX2, HMMR, and ANLN were identified as recessive miR-126-related genes that may be involved in NSCLC. CONCLUSIONS: MiR-126 plays an essential role in the biological processes of NSCLC through binding to target genes and influences the prognosis of patients with the disease.

The expression of high-mobility group protein box 1 correlates with the progression of non-small cell lung cancer.

High-mobility group protein box 1 (HMGB1) released from dying tumor cells promotes tumor progression, on the other hand HMGB1 activates dendritic cells and triggers anti-neoplastic response of T-cells in chemotherapy and radiotherapy. HMGB1 expression is up-regulated in many kinds of tumors. To investigate HMGB1 expression in non-small cell lung cancer, 63 patients were enrolled and tumor tissues were collected with matched normal lung tissues. HMGB1 mRNA and protein levels were quantified with real-time PCR, Western blots and immunohistochemistry. The HMGB1 expression in tumor tissue was lower than in matched normal lung tissue at mRNA levels (Paired t-test, t<0.001) and the down-regulation in stage III-IV patients was also significantly greater than one in stage I-II (one-way ANOVA, p=0.005). At protein level, HMGB1 expression was also down-regulated. Low HMGB1 expression in non-small cell lung cancer may explain the poor therapeutical outcome during chemotherapy and radiotherapy.

Nanobody against the E7 oncoprotein of human papillomavirus 16.

The persistent infection of high-risk human papillomavirus (HPV) is one of the most common causes of cervical cancer. It is well documented that expression of two oncogenes (E6/E7) plays a key role in tumor progression. HPV16E7 -targeting via nanobody (Nb) therefore could be beneficial for HPV16-associated cancer diagnosis and therapy. In this work, phage-display approach was employed to select the high affinity HPV16E7-specific Nb. Firstly; a high-quality immune library was constructed. After three round of biopanning, high-affinity HPV16 E7-specific nanobodies were retrieved. By phage ELISA and sequencing, four different sequences of anti- HPV16E7 nanobodies were selected. Then recombinant nanobody Nb2 was cloned and expressed in E. coli, and the specificity and thermal stability of purified Nb2 was evaluated. To examine the potential of Nb2 as an inhibitor of E7 function, Nb2 was expressed within HPV16 positive cells. Proliferation assay showed that the intracellular expressed Nb2 as an intrabody can decrease the growth of HPV16-positive cells. The results indicate that Nb2 as an intracellular antibody directed towards HPV oncoprotein E7 has great promise in applications for the therapy of HPV16-associated disease.

[Impact of gastric tube diameter on quality of life of esophagus cancer patient after Ivor-Lewis esophagectomy].

OBJECTIVE: To explore the impact of the gastric tube diameter on quality of life of esophagus cancer patients after Ivor-Lewis esophagectomy. METHODS: Clinical and follow-up data of 188 esophageal cancer patients who underwent Ivor-Lewis esophagectomy at Department of Cardio-Thoracic Surgery, Drum Tower Clinical Medicine College, Nanjing Medical University from January 2015 to June 2016 were retrospectively analyzed. Inclusion criteria included age <75 years old, good foundation health situation, no distant metastasis, complete follow-up data for one-year after surgery, and middle-lower esophageal squamous cell carcinoma (ESCC). According to the diameter of gastric tube formed during operation, 92 patients were assigned to narrow gastric tube group (NGT group, ≥2 cm to <4 cm), which were further divided into narrower group (≥2 cm to <3 cm, n=44) and medium narrow group (≥3 cm to <4 cm, n=48); 96 patients were assigned to wide gastric tube group(WGT group, ≥4 cm), which were further divided into medium wide group(≥4 cm to <5 cm, n=50) and wider group(≥5 cm, n=46). Postoperative patients were followed up by telephone or outpatient service for one year and then re-hospitalized to receive associated examinations, including lung function test, esophageal pressure measurement, 24-hour esophageal dynamic pH monitoring (total number of pH<4, number of pH<4 lasting more than 5 minutes, maximum duration of pH<4 and time percentage of pH<4) and dilatation measurement of gastric tube (the diameter measured by CT minus the diameter measured in surgery). During follow-up, postoperative quality of life(QoL) was assessed by questionnaire. These contents were compared and plotted as a chart. RESULTS: There were no statistically significant differences between NGT group and WGT group regard to preoperative baseline information, postoperative pathology and postoperative complications (residual gastric leakage, anastomotic leakage, anastomotic stenosis, pulmonary complications, atrial fibrillation and chylothorax) (all P>0.05). Compared with WGT group, the NGT group had better postoperative lung function, including percentage of vital capacity [(76.4±6.8)% vs. (73.2±7.7)%, t=2.168, P=0.033], percentage of maximal voluntary ventilation [(72.7±6.4)% vs. (69.3±6.8)%, t=2.409, P=0.018] and percentage of forced expiratory volume in the first second [(69.2±5.0)% vs. (66.7±6.2)%, t=2.033, P=0.045], higher plane pressure of anastomotic stoma [(5.4±3.1) mmHg vs. (4.2±2.4) mmHg, t=2.083, P=0.038], greater dilatation of gastric tube [(1.0±0.4) cm vs. (0.5±0.3) cm, t=5.888, P=0.000], milder gastroesophageal reflux according to the indices of 24-hour esophageal dynamic pH monitoring, including the total number of pH<4 (228.3±65.3 vs. 280.8±103.9, t=-2.920,P=0.004), the number of pH<4 lasting more than 5 minutes (19.9±8.5 vs. 30.6±15.6, t=-4.127,P=0.000), the maximum duration of pH<4[(32.5±9.4) minutes vs. (37.9±13.6) minutes, t=-2.232,P=0.028] and the time percentage of pH<4 [(23.4±10.2)% vs. (28.4±10.6)%, t=-2.303, P=0.024]. However, no significant difference was found in the scores of postoperative QoL between the two groups(P=0.051). According to the pairwise comparisons among the four subgroups, narrower group showed better performance on postoperative lung function, plane pressure of anastomotic stoma, the dilatation of gastric tube, indices of 24-hour esophageal dynamic pH monitoring and scores of postoperative QoL as compared to wider group (all P<0.05). There were no statistically significant differences among medium narrow group, medium wide group and wider group. Line charts showed that the larger of the gastric tube diameter, the worse of the postoperative lung function, the more severe of gastroesophageal reflux and the smaller degree of gastric tube dilatation. CONCLUSION: Narrow gastric tube with a diameter of 2-4 cm can improve the postoperative QoL of esophagus cancer patients after Ivor-Lewis esophagectomy without increasing the risk of postoperative complications.

Novel heterozygous NOTCH3 pathogenic variant found in two Chinese patients with CADASIL.

NOTCH3 mutations have been described to cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Here, we report 2 CADASIL patients from a Chinese family. Whole genome sequencing was performed on the two CADASIL patients. The novel variant c.128G>C in exon 2 of NOTCH3 was identified and confirmed through PCR-Sanger sequencing (Human Genome Variation Society nomenclature: HGVS: NOTCH3 c.128G>C; p.Cys43Ser). The heterozygous NOTCH3 variant cause a cysteine to serine substitution at codon 43. According to the variant interpretation guideline of American College of Medical Genetics and Genomics (ACMG), this variant was classified as "pathogenic". Other variants in HTRA1, COL4A1 and COL4A2 were also found, they were classified as "benign".