Diagnose and treatment for Type D congenital esophageal atresia with tracheoesophageal fistula.

Importance: Type D esophageal atresia (EA) with tracheoesophageal fistula (TEF) is characterized by EA with both proximal and distal TEFs. It is a rare congenital anomaly with a very low incidence. Objective: To investigate diagnostic and treatment strategies for this rare condition. Methods: We retrospectively reviewed the clinicopathological features of patients with EA/TEF treated at our institution between January 2007 and September 2021. Results: Among 386 patients with EA/TEF, 14 (3.6%) had type D EA/TEF. Only two patients were diagnosed with proximal TEF preoperatively. Seven patients were diagnosed intraoperatively. Five patients were missed for diagnosis during the initial surgery but was later confirmed by bronchoscopy. During the neonatal period, seven patients underwent a one-stage repair of proximal and distal TEF via thoracoscopy or thoracotomy. Due to missed diagnosis and other reasons, the other 7 patients underwent two-stage surgery for repair of the proximal TEF, including cervical incision and thoracoscopy. Ten of the 14 patients experienced postoperative complications including anastomotic leakage, pneumothorax, esophageal stricture, and recurrence. Patients who underwent one-stage repair of distal and proximal TEF during the neonatal period showed a higher incidence of anastomotic leak (4/7). In contrast, only one of seven patients with two-stage repair of the proximal TEF developed an anastomotic leak. Interpretation: Type D EA/TEF is a rare condition, and proximal TEFs are easily missed. Bronchoscopy may aim to diagnose and determine the correct surgical approach. A cervical approach may be more suitable for repairing the proximal TEF.

Blockade of V-domain immunoglobulin suppressor of T-cell activation reprograms tumour-associated macrophages and improves efficacy of PD-1 inhibitor in gastric cancer.

BACKGROUND AND AIMS: In gastric cancer, the response rate of programmed cell death protein-1 (PD-1) inhibitor is far from satisfactory, indicating additional nonredundant pathways might hamper antitumour immunity. V-domain immunoglobulin suppressor of T-cell activation (VISTA) has been reported in several malignancies as a novel immune-checkpoint. Nevertheless, the role of VISTA in gastric cancer still remains obscure. Our purpose is to explore the clinical significance and potential mechanism of VISTA in affecting gastric cancer patients' survival and immunotherapeutic responsiveness. METHODS: Our study recruited eight independent cohorts with a total of 1403 gastric cancer patients. Immunohistochemistry, multiplex immunofluorescence, flow cytometry or intracellular flow cytometry, quantitative polymerase chain reaction, western blotting, fluorescence-activated cell sorting, magnetic-activated cell sorting, smart-seq2, in vitro cell co-culture and ex vivo tumour inhibition assays were applied to investigate the clinical significance and potential mechanism of VISTA in gastric cancer. RESULTS: VISTA was predominantly expressed on tumour-associated macrophages (TAMs), and indicated poor clinical outcomes and inferior immunotherapeutic responsiveness. VISTA+ TAMs showed a mixed phenotype. Co-culture of TAMs and CD8+ T cells indicated that VISTA+ TAMs attenuated effective function of CD8+ T cells. Blockade of VISTA reprogrammed TAMs to a proinflammatory phenotype, reactivated CD8+ T cells and promoted apoptosis of tumour cells. Moreover, blockade of VISTA could also enhance the efficacy of PD-1 inhibitor, suggesting that blockade of VISTA might synergise with PD-1 inhibitor in gastric cancer. CONCLUSIONS: Our data revealed that VISTA was an immune-checkpoint associated with immunotherapeutic resistance. Blockade of VISTA reprogrammed TAMs, promoted T-cell-mediated antitumour immunity, and enhanced efficacy of PD-1 inhibitor, which might have implications in the treatment of gastric cancer.

Gaussian Boson Sampling with Pseudo-Photon-Number-Resolving Detectors and Quantum Computational Advantage.

We report new Gaussian boson sampling experiments with pseudo-photon-number-resolving detection, which register up to 255 photon-click events. We consider partial photon distinguishability and develop a more complete model for the characterization of the noisy Gaussian boson sampling. In the quantum computational advantage regime, we use Bayesian tests and correlation function analysis to validate the samples against all current classical spoofing mockups. Estimating with the best classical algorithms to date, generating a single ideal sample from the same distribution on the supercomputer Frontier would take ∼600 yr using exact methods, whereas our quantum computer, Jiǔzhang 3.0, takes only 1.27 µs to produce a sample. Generating the hardest sample from the experiment using an exact algorithm would take Frontier∼3.1×10^{10} yr.

Redundant and scattered genetic determinants for coumarin biodegradation in Pseudomonas sp. strain NyZ480.

Coumarin (COU) is both a naturally derived phytotoxin and a synthetic pollutant which causes hepatotoxicity in susceptible humans. Microbes have potentials in COU biodegradation; however, its underlying genetic determinants remain unknown. Pseudomonas sp. strain NyZ480, a robust COU degrader, has been isolated and proven to grow on COU as its sole carbon source. In this study, five homologs of xenobiotic reductase A scattered throughout the chromosome of strain NyZ480 were identified, which catalyzed the conversion of COU to dihydrocoumarin (DHC) in vitro. Phylogenetic analysis indicated that these COU reductases belong to different subgroups of the old yellow enzyme family. Moreover, two hydrolases (CouB1 and CouB2) homologous to the 3,4-dihydrocoumarin hydrolase in the fluorene degradation were found to accelerate the generation of melilotic acid (MA) from DHC. CouC, a new member from the group A flavin monooxygenase, was heterologously expressed and purified, catalyzing the hydroxylation of MA to produce 3-(2,3-dihydroxyphenyl)propionate (DHPP). Gene deletion and complementation of couC indicated that couC played an essential role in the COU catabolism in strain NyZ480, considering that the genes involved in the downstream catabolism of DHPP have been characterized (Y. Xu and N. Y. Zhou, Appl Environ Microbiol 86:e02385-19, 2020) and homologous catabolic cluster exists in strain NyZ480. This study elucidated the genetic determinants for complete degradation of COU by Pseudomonas sp. strain NyZ480.IMPORTANCECoumarin (COU) is a phytochemical widely distributed in the plant kingdom and also artificially produced as an ingredient for personal care products. Hence, the environmental occurrence of COU has been reported in different places. Toxicologically, COU was proven hepatotoxic to individuals with mutations in the CYP2A6 gene and listed as a group 3 carcinogen by the International Agency for Research on Cancer and thus has raised increasing concerns. Until now, different physicochemical methods have been developed for the removal of COU, whereas their practical applications were hampered due to high cost and the risk of secondary contamination. In this study, genetic evidence and biochemical characterization of the COU degradation by Pseudomonas sp. strain NyZ480 are presented. With the gene and strain resources provided here, better managements of the hazards that humans face from COU could be achieved, and the possible microbiota-plant interaction mediated by the COU-utilizing rhizobacteria could also be investigated.

Clinical characteristics and prognosis of 69 cases of neonatal appendicitis.

Importance: Neonatal appendicitis (NA) is a rare and potentially fatal neonatal disease. However, misdiagnosis is common owing to atypical clinical manifestations and non-specific laboratory tests. Objective: The aim of this study was to summarize the clinical characteristics, treatments, and prognoses of infants with NA. Methods: This retrospective analysis included 69 patients diagnosed with NA admitted to Beijing Children's Hospital between 1980 and 2019. The patients were divided into surgical and non-surgical groups based on whether surgery was performed. Their clinical characteristics were analyzed using the chi-square test, t-test, or the Mann-Whitney U test. Results: The study included 47 males and 22 females with NA. The primary symptoms were abdominal distension (n = 36, 52.2%), fever (n = 19, 27.5%), refusal to feed or decreased feeding (n = 16, 23.2%), and vomiting (n = 15, 21.7%). Sixty-five patients underwent abdominal ultrasound examinations; 43 had definite appendiceal abnormalities, 10 had right lower abdominal adhesive masses, and 14 had neonatal enterocolitis manifestations. Twenty-nine and 40 patients were in the surgical and non-surgical groups, respectively. No statistically significant differences were observed between the groups regarding sex, age at onset, birth weight, admission weight, or hospitalization time. However, parenteral nutrition was prolonged in the surgical group (P = 0.001). Additionally, two patients (2.9%) died. Interpretation: NA is a rare neonatal disease with atypical clinical manifestations. Abdominal ultrasonography may aid in the diagnosis. Similarly, appropriate treatment can improve the prognosis.

Elucidation of the coumarin degradation by Pseudomonas sp. strain NyZ480.

As a phytotoxin and synthetic chemical, coumarin (COU) is known for its hepatotoxicity and carcinogenicity. However, no thorough characterization of its microbial degradation has been reported. Here, Pseudomonas sp. strain NyZ480 was isolated for its capability of utilizing COU as the sole carbon source. Studies on its growth and degradation efficiency of COU under various conditions suggested that strain NyZ480 performed the optimum degradation at 30 â„ƒ, pH 7, and 0.5 mM COU was completely removed within 4 h with 1% inoculum. HPLC and LC-MS analyses indicated that dihydrocoumarin (DHC), melilotic acid (MA) and 3-(2,3-dihydroxyphenyl)propionate (DHPP) were the upstream biotransformation intermediates of COU. Enzyme assay established that the initial reaction transforming COU to DHC required an NAD(P)H-dependent reductase, followed by the hydrolysis of DHC to generate MA, and the third reaction catalyzing the monooxygenation of MA to DHPP utilized a strict NADH-dependent hydroxylase. Combining genomics and transcriptomics, we proposed that the COU downstream degradation (from DHPP) was catalyzed by enzymes encoded by a gene cluster homologous to the mhp cluster for 3(3-hydroxyphenyl)propionate degradation via DHPP in E. coli. This study thoroughly identified the intermediates from the COU catabolism, providing essential insights into the molecular evidences of its biodegradation pathway.

Solving Graph Problems Using Gaussian Boson Sampling.

Gaussian boson sampling (GBS) is not only a feasible protocol for demonstrating quantum computational advantage, but also mathematically associated with certain graph-related and quantum chemistry problems. In particular, it is proposed that the generated samples from the GBS could be harnessed to enhance the classical stochastic algorithms in searching some graph features. Here, we use Jiǔzhang, a noisy intermediate-scale quantum computer, to solve graph problems. The samples are generated from a 144-mode fully connected photonic processor, with photon click up to 80 in the quantum computational advantage regime. We investigate the open question of whether the GBS enhancement over the classical stochastic algorithms persists-and how it scales-with an increasing system size on noisy quantum devices in the computationally interesting regime. We experimentally observe the presence of GBS enhancement with a large photon-click number and a robustness of the enhancement under certain noise. Our work is a step toward testing real-world problems using the existing noisy intermediate-scale quantum computers and hopes to stimulate the development of more efficient classical and quantum-inspired algorithms.

Microbial Diversity Biased Estimation Caused by Intragenomic Heterogeneity and Interspecific Conservation of 16S rRNA Genes.

The 16S rRNA gene has been extensively used as a molecular marker to explore evolutionary relationships and profile microbial composition throughout various environments. Despite its convenience and prevalence, limitations are inevitable. Variable copy numbers, intragenomic heterogeneity, and low taxonomic resolution have caused biases in estimating microbial diversity. Here, analysis of 24,248 complete prokaryotic genomes indicated that the 16S rRNA gene copy number ranged from 1 to 37 in bacteria and 1 to 5 in archaea, and intragenomic heterogeneity was observed in 60% of prokaryotic genomes, most of which were below 1%. The overestimation of microbial diversity caused by intragenomic variation and the underestimation introduced by interspecific conservation were calculated when using full-length or partial 16S rRNA genes. Results showed that, at the 100% threshold, microbial diversity could be overestimated by as much as 156.5% when using the full-length gene. The V4 to V5 region-based analyses introduced the lowest overestimation rate (4.4%) but exhibited slightly lower species resolution than other variable regions under the 97% threshold. For different variable regions, appropriate thresholds rather than the canonical value 97% were proposed for minimizing the risk of splitting a single genome into multiple clusters and lumping together different species into the same cluster. This study has not only updated the 16S rRNA gene copy number and intragenomic variation information for the currently available prokaryotic genomes, but also elucidated the biases in estimating prokaryotic diversity with quantitative data, providing references for choosing amplified regions and clustering thresholds in microbial community surveys. IMPORTANCE Microbial diversity is typically analyzed using marker gene-based methods, of which 16S rRNA gene sequencing is the most widely used approach. However, obtaining an accurate estimation of microbial diversity remains a challenge, due to the intragenomic variation and low taxonomic resolution of 16S rRNA genes. Comprehensive examination of the bias in estimating such prokaryotic diversity using 16S rRNA genes within ever-increasing prokaryotic genomes highlights the importance of the choice of sequencing regions and clustering thresholds based on the specific research objectives.

Surgical management strategy of alimentary tract duplication involving the rectum in children.

PURPOSE: Alimentary tract duplication involving the rectum (ATD-R) is rare. The purpose of the study was to describe the features of pediatric ATD-R patients and propose a surgical management strategy. METHODS: Nine consecutive children operated on for ATD-R at a tertiary center for pediatrics from January 2010 to June 2021 were retrospectively reviewed and followed up. Eighty-six children with the same diagnosis from the literature were reviewed to assist the investigation. Classifications of ATD-R consisted of cystic, tubular, and diverticular. RESULTS: Surgical treatment and histopathological examination identified six females and three males with ATD-R. Initial clinical symptoms included perianal lesions, abnormal discharge, and anorectal malformation (ARM). Apart from one tubular ATD-R patient with cloaca malformation, the other eight patients had normal-developed anorectum. Complete or partial lesion resection maintaining the integrity of the proper colorectum was a principle of surgery. Six patients were followed up for a median time of 71 (range 12-121) months with good prognoses. A surgical management strategy of ATD-R in children was proposed. CONCLUSIONS: ATD-R commonly occurred concurrently with normal-developed anorectum, seldom combined with ARM. ATD-R should be considered as a differential diagnosis in anorectal symptoms. The timely and appropriate operation was curative.

The Chinese Mandarin Version of the Esophageal-Atresia-Quality-of-Life Questionnaires for Children and Adolescents: Evaluation of Linguistic and Content Validity.

BACKGROUND: After repair of esophageal atresia (EA), children risk digestive and respiratory morbidity, but knowledge of their health-related quality of life (HRQOL) in China is lacking. The EA-QOL questionnaires were developed in Sweden and Germany to evaluate condition-specific HRQOL in children with EA aged 2-7 and 8-17. This study aimed to evaluate the linguistic and content validity of the Chinese Mandarin version of the EA-QOL questionnaires. METHODS: The procedure was conducted in compliance with international standards, including a forward-backward translation procedure, expert reviews, and cognitive debriefing interviews with 14 Chinese families of children with EA (parents of 8 children aged 2-7/6 children aged 8-17 and their parents). RESULTS: Following forward-backward translation, minor issues were identified and solved. In interviews, all participants rated all EA-QOL items easy to understand, none expressed negative emotions about them and most described them comprehensive and relevant for EA. Leading from cognitive debriefing, three EA-QOL items in the questionnaire version for children aged 2-7 and three EA-QOL items in the questionnaire version for children aged 8-17 were modified in the Chinese language to improve cultural appropriateness and/or clarity. CONCLUSION: The Chinese Mandarin version of the EA-QOL questionnaires achieved satisfactory linguistic and content validity. This can help increase focus of HRQOL in research and clinical practice of children with EA in China.

Comprehensive Analysis of Gut Microbiota and Fecal Bile Acid Profiles in Children With Biliary Atresia.

Background: Biliary atresia (BA) is the most common cholestatic liver disease in neonates. Herein, we aimed at characterizing the gut microbiota and fecal bile acid profiles of BA patients, defining the correlations between them, and evaluating the relationship between the clinical pathogenesis and changes in the gut microbiota and bile acid profiles. Methods: A total of 84 fecal samples from BA patients (n = 46) and matched healthy controls (HCs, n = 38) were subjected to sequencing by 16S rRNA gene amplification, and fecal bile acid were analyzed by targeted metabolomics. Findings: Compared with the controls, a structural separation of the intestinal flora of BA patients was uncovered, which was accompanied by changes in the composition of fecal bile acids. In the BA group, Actinobacillus, Monoglobus, and Agathobacter were enriched in patients without cholangitis (p < 0.05). Selenomonadaceae and Megamonas were more abundant in patients without recurrent cholangitis episodes (p < 0.05), while Lachnospiraceae and Ruminococcaceae were enriched in patients with multiple recurrences of cholangitis (p < 0.05). Postoperative jaundice clearance was associated with Campylobacter and Rikenellaceae (p < 0.05), and tauroursodeoxycholic acid was associated with jaundice clearance (p < 0.001). Conclusion: BA patients are characterized by different compositions of gut microbiota and bile acids, and their interaction is involved in the process of liver damage in BA, which may be closely related to the occurrence of postoperative cholangitis and jaundice clearance.

Erratum: MiR-206 suppresses the deterioration of intrahepatic cholangiocarcinoma and promotes sensitivity to chemotherapy by inhibiting interactions with stromal CAFs: Erratum.

[This corrects the article DOI: 10.7150/ijbs.62602.].

Growth assessments for children with recurrent tracheoesophageal fistulas.

PURPOSE: To assess the growth status of children with recurrent tracheoesophageal fistula (rTEF), and determine the possible risk factors of growth retardation (GR). METHODS: The medical records of 83 patients with rTEF who underwent surgical repair were retrospectively analyzed. The patients were retrospectively divided into two groups according to whether they had GR. The clinical variables were compared between the GR and non-GR groups. Univariate and multivariable logistic regression analysis were performed to identify the risk factors for GR. RESULTS: Eighty-three children diagnosed with rTEF were included in this study. After a median follow-up of 31.4 (19.8, 48.7) months, GR occurred in 28 patients (33.7%). Among them, six patients with only weight for age Z score (WAZ) < -2SD, five patients with only height for age Z score (HAZ) < -2SD, and six patients with only BMI for age Z score (BAZ) < -2SD, while seven patients with both WAZ and HAZ < -2SD and four patients with both WAZ, HAZ and BAZ < -2SD. Multivariate logistic regression analysis showed that birth weight, anastomotic stricture and dysphagia after rTEF repair were independent risk factors with OR of 0.325 (0.119, 0.891), 4.396 (1.451, 13.324) and 5.341 (1.153, 24.752) for GR, respectively. CONCLUSIONS: GR is a common complication after rTEF repair. Birth weight, anastomotic stricture and dysphagia after rTEF repair are independent risk factors affecting growth.

Esophageal elongation by bougienage and delayed primary thoracoscopic anastomosis for pure esophageal atresia without tracheoesophageal fistula.

PURPOSE: We aim to share our experience of esophageal elongation by bougienage and delayed primary thoracoscopic anastomosis for pure esophageal atresia (EA) without tracheoesophageal fistula (TEF). METHODS: Fifteen patients with pure EA treated with delayed primary thoracoscopic anastomosis combined with or without esophageal elongation by bougienage were retrospectively analyzed. RESULTS: Four patients were managed without bougienage, and their surgical repair was performed thoracoscopically after natural esophageal growth. Among the remaining 11 patients, the average tension-free distance before elongation was 5 (4.5-6) vertebral bodies, and the mean age at the start and end of the bougienage period was 123 (63-280) days and 173 (106-350) days, respectively, with an average duration of 50 (29-82) days. The average age at the definitive operation in this series was 184 (107-385) days, with a mean operative duration of 186 (95-300) min. Neither anastomotic leakage nor TEF occurred, and oral feeding was partially or completely established in 13 patients during hospitalization. Among all patients, one was lost to follow-up, and others were followed up with an average duration of 47.7 (9.8-97.1) months. All patients had different degrees of anastomosis stricture, and 8 patients had gastroesophageal reflux. Oral feeding was completely established in 12 patients; however, tube feeding was required in 2 patients. CONCLUSIONS: The management of pure EA is complicated and inconclusive. Esophageal elongation by bougienage and delayed primary thoracoscopic anastomosis for long-gap pure EA without TEF is safe and effective.

Indocyanine green localization for laparoscopic duodenal web excision.

BACKGROUND: A duodenal web refers to partial or complete obstruction of the duodenum due to a membranous web. When looking at the serosal side of the intestine during duodenal web excision, especially during laparoscopic surgery, determining the web origin might be challenging. This study aimed to determine the efficacy of intraduodenum indocyanine green injection and near-infrared light during laparoscopic surgery in enhancing the ability to identify duodenal web localization. METHODS: We used intraduodenum indocyanine green injection to unequivocally recognize the duodenal web and facilitate laparoscopic excision. The clinical analysis was based on a male neonatal case with duodenal web admitted to our hospital. After the patient was placed in the supine position, 5 mL of ICG was injected via a 6-Fr nasogastric tube. The fluorescence was visualized in the white light and near-infrared light dual-mode of the camera system, localizing the duodenal precisely and in real-time. RESULTS: Laparoscopically, the duodenal web was accurately identified and removed with intraduodenum indocyanine green visualization under near-infrared light. The procedure was completed successfully, and the patient showed good postoperative outcomes. CONCLUSIONS: Intraduodenum indocyanine green injection during laparoscopic surgery is a feasible adjuvant for duodenal web localization, showing improvements in terms of outcomes compared to previous methods of determining the duodenal web location.

The largest report on thoracoscopic surgery for recurrent tracheoesophageal fistula after esophageal atresia repair.

BACKGROUND: Although thoracoscopic surgery has become the routine surgical method for esophageal atresia/tracheoesophageal fistula (EA/TEF), thoracoscopic treatment for recurrent tracheoesophageal fistula (rTEF) is far from popularized. OBJECTIVES: We aimed to explore the safety and efficacy of thoracoscopic treatment for rTEF with a large-cohort study. METHODS: We retrospectively analyzed the clinical characteristics and outcomes of 103 consecutive patients who underwent thoracoscopic surgery for rTEF by one surgeon after EA/TEF repair at two different institutions in China from 2014 to 2021. RESULTS: One hundred and three pediatric patients (67 boys) were enrolled and the primary operations were performed via thoracoscopic (n = 75, 72.82%) or open surgery (n = 28, 27.18%). The median age at rTEF diagnosis was 5 (3, 10) months after the primary repair. Patients were diagnosed with recurrent fistula to the trachea (n = 97, 94.17%), bronchi (n = 4, 3.88%), and lung parenchyma (n = 2, 1.94%), and all of them underwent thoracoscopic surgery at a median age of 7 (5, 14) months with a median weight of 6200 (4870, 7650) g. After the repair of rTEF, the incidence of esophageal leakage, esophageal stricture, and TEF recurrence were 12.8%, 33.4%, and 10.8%, respectively. After the follow-up, 87 patients survived, 6 died, and 10 were lost to follow-up. CONCLUSIONS: The results of thoracoscopic surgery for rTEF were comparable with previously reported thoracotomy surgery. Owing to the clear field during the operation, rapid patient recovery and esthetic results, the thoracoscopic approach could be a better choice for experienced pediatric surgeons. LEVEL OF EVIDENCE: LEVEL IV.

MGP promotes CD8+ T cell exhaustion by activating the NF-κB pathway leading to liver metastasis of colorectal cancer.

Matrix Gla protein (MGP) was originally reported as a physiological suppressor of ectopia calcification and has also been reported to be associated with cancer. However, the relation between the biological functions of MGP and the immune response in colorectal cancer (CRC) remains unclear. Here, we investigated the regulatory role of MGP in the immune microenvironment of CRC. MGP expression in CRC samples was assessed by single-cell RNA sequencing and the Gene Expression Omnibus (GEO) database, and confirmed by quantitative real-time Polymerase Chain Reaction (qRT-PCR) and immunohistochemistry analysis of human CRC samples. The effect of MGP on proliferation and invasion of CRC cells was evaluated by in vitro assays involving MGP knockdown and overexpression. Luciferase reporter assay and chromatin immunoprecipitation (ChIP)-qPCR assay were performed to identify transcriptional regulatory sites of the nuclear factor kappa-B (NF-κB) and programmed cell death ligand 1 (PD-L1). In vivo experiments were performed in mouse model of CRC liver metastasis established via spleen injection. The results revealed that MGP was significantly upregulated in cancer cell clusters from the primary CRC or liver metastases, compared with that in the corresponding paracancerous tissues via single-cell RNA sequencing. MGP enriched intracellular free Ca2+ levels and promoted NF-κB phosphorylation, thereby activated PD-L1 expression to promote CD8+ T cell exhaustion in CRC. The luciferase reporter assay and ChIP-qPCR assay indicated that the transcriptional regulation of NF-κB upregulated PD-L1 expression. In vivo, MGP inhibition significantly decreased the rate of CRC liver metastasis, which was further reduced after combined therapy with αPD1 (anti-PD1). In conclusions, this study revealed that MGP can facilitate CD8+ T cell exhaustion by activating the NF-κB pathway, leading to liver metastasis of CRC. The combination of MGP knockdown and αPD1 can synergistically resist liver metastasis of CRC.

Thoracoscopic repair for esophageal pulmonary fistula after esophageal atresia repair.

BACKGROUND: Esophageal pulmonary fistula is a special type of acquired tracheoesophageal fistula that occurs after esophageal atresia/tracheoesophageal fistula repair. Thoracotomy is the surgical repair method currently in use, but postoperative outcomes are unclear. Therefore, we aimed to explore the preliminary safety, effectiveness, and feasibility of thoracoscopic surgical repair of esophageal pulmonary fistula. METHODS: We retrospectively collected data from all patients with esophageal atresia/tracheoesophageal fistula at Beijing Children's Hospital from January 2017 to October 2021, and the clinical characteristics of patients with esophageal pulmonary fistula were analyzed. Clinical information was recorded, and follow-up was performed. RESULTS: Seven patients (five boys and two girls) were diagnosed as esophageal pulmonary fistula. All patients underwent multiple esophageal surgeries and had esophageal strictures before surgical repair. Clinical manifestations included cough, expectoration, and recurrent pneumonia. Esophagography indicated the location of the fistula with a 100% positive rate, while the positive rate of flexible bronchoscopy and chest computed tomography was 57% (4/7) and 43% (3/7), respectively. Surgical repair was achieved using thoracoscopy with an average operation time of 172 min. All patients developed esophageal strictures, four of which had refractory esophageal strictures and underwent esophageal dilations ranged from 5 to 56 times before this surgery, but anastomotic leakage or acquired esophageal pulmonary fistulas were absent post-surgery. After a median follow-up of 22 months, all patients survived, and the symptoms were well controlled. CONCLUSIONS: Esophageal pulmonary fistula is a rare complication of atresia/tracheoesophageal fistula repair. Thoracoscopic surgery is still possible even after previous multiple surgeries in the chest with significant complications and satisfactory results can be achieved in the short term. LEVEL OF EVIDENCE: Level III.

MiR-206 suppresses the deterioration of intrahepatic cholangiocarcinoma and promotes sensitivity to chemotherapy by inhibiting interactions with stromal CAFs.

Background: Intrahepatic cholangiocarcinoma (iCCA) is a highly malignant subtype of cholangiocarcinoma (CCA) with poor prognosis. In iCCA, the interplay between the stroma and tumor cells results in resistance to adjuvant chemotherapy. Increasing evidence indicates that miR-206 participates in tumor progression, but its role in iCCA is still unclear. The aim of this study was to identify dysregulated miR-206 expression in iCCA and to further explore the underlying mechanism. Methods: MiR-206 expression was proven to be downregulated in iCCA tissues by qPCR, and its correlation with clinical characteristics and prognosis was investigated. iCCA-derived cancer-associated fibroblast cells (CAFs) and normal fibroblast cells (NFs) were isolated and identified. MiR-206 was knocked in or down in CAFs and CCA cells, respectively, to explore the role of miR-206, and coculture of these treated CCAs and CAFs was conducted to explore the effects of miR-206 on their mutual promoting effects. Exosomes carrying miR-206 and an orthotopic mouse model were used to determine the inhibitory effects of miR-206 on iCCA deterioration in vivo. Results: We confirmed that miR-206 is a suppressor of iCCA. Overexpressing miR-206 in CCA cells inhibited cell proliferation, migration and invasion. When cocultured with CCA cells, NFs downregulated miR-206 expression, and NFs were susceptible to transforming into CAFs. Moreover, CAFs promoted CCA cell malignant behaviors and gemcitabine resistance. Overexpressing miR-206 in CAFs or CCA cells inhibited this mutual promoting effect. Additionally, when delivered by exosomes, miR-206 suppressed tumor deterioration. And combined with gemcitabine, this treatment resulted in a longer survival time. Conclusion: Our study explained that the interaction between CCA cells and CAFs promoted iCCA deterioration. As a suppressive factor, miR-206 inhibited aggressive characteristics and gemcitabine resistance by interfering with this mutual promoting effect. This research elucidated the molecular mechanism underlying the unfavorable chemotherapeutic response of patients with iCCA, which provided a promising target for iCCA treatment.