Primary Mediastinal Large B-Cell Lymphoma Achieved by Non-Cautery Assisted Transbronchial Mediastinal Cryobiopsy.

Transbronchial mediastinal cryobiopsy is a novel sampling strategy that shows improved diagnostic utility for mediastinal lesions, particularly in rare tumors and benign disorders, as compared to standard endobronchial ultrasound-guided transbronchial needle aspiration. During this procedure, electrocautery incision is frequently needed to advance the cryoprobe through the airway into the mediastinal lesion, which however results in increased operative difficulty and prolonged procedural time. Here we present a case of mediastinal large B-cell lymphoma successfully diagnosed by transbronchial mediastinal cryobiopsy without cautery-induced airway incision.

Mediastinal Nodular Lymphocyte Predominant Hodgkin Lymphoma Achieved by Endoscopic Transesophageal Cryobiopsy.

Guidelines have recommended endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine-needle aspiration biopsy as initial sampling approaches of mediastinal lymph nodes for lung cancer staging. However, the small sample volume might restrict the diagnostic utility of needle aspiration in certain mediastinal diseases. We have recently shown that transbronchial mediastinal cryobiopsy, which is capable of providing larger amounts of intact tissue, improves diagnostic yield in rare tumors and benign diseases compared to EBUS-TBNA. Here, we present a case of mediastinal nodular lymphocyte predominant Hodgkin lymphoma successfully diagnosed by endoscopic transesophageal cryobiopsy.

Endobronchial Ultrasound-Guided Transbronchial Incision and Drainage in the Treatment of Mediastinal Abscess.

Mediastinal abscess, mostly resulting from esophageal perforation or cardiothoracic surgery, is a serious condition carrying high morbidity and mortality. Antibiotic therapy alone normally did not achieve a satisfactory outcome, due to poor circulation of abscess that hampers drug delivery. Surgical intervention for debridement and drainage is recommended, but it poses a high risk in patients with poor health status and could lead to various complications. Recent studies proposed endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) as an effective alternative to surgery; however, repeated TBNA procedures are usually needed for complete clearance of the lesion, thus causing increased patient suffering and medical expenses. Here, we present the first case of successful application of EBUS-guided transbronchial incision and drainage, which provides a novel, safe, and effective treatment for patient with mediastinal abscess unwilling or unsuitable to undergo surgical intervention.

Transbronchial mediastinal cryobiopsy in the diagnosis of mediastinal lesions: a randomised trial.

BACKGROUND: Guidelines recommend endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) as an initial investigatory technique for mediastinal nodal staging in lung cancer. However, EBUS-TBNA can be limited by the inadequacy of intact tissues, which might restrict its diagnostic yield in mediastinal lesions of certain aetiologies. We have previously shown that EBUS-guided transbronchial mediastinal cryobiopsy can provide intact samples with greater volume. METHODS: This randomised study determined the diagnostic yield and safety of transbronchial mediastinal cryobiopsy monitored by endosonography for the diagnosis of mediastinal lesions. Patients with a mediastinal lesion of ≥1 cm in the short axis were recruited. Following identification of the mediastinal lesion by linear EBUS, fine-needle aspiration and cryobiopsy were sequentially performed in a randomised order. Primary end-points were diagnostic yield, defined as the percentage of patients for whom mediastinal biopsy provided a definite diagnosis, and procedure-related adverse events. RESULTS: In total, 197 patients were enrolled and randomly allocated. The overall diagnostic yield was 79.9% and 91.8% for TBNA and transbronchial mediastinal cryobiopsy, respectively (p=0.001). Diagnostic yields were similar for metastatic lymphadenopathy (94.1% versus 95.6%, p=0.58), while cryobiopsy was more sensitive than TBNA in uncommon tumours (91.7% versus 25.0%, p=0.001) and benign disorders (80.9% versus 53.2%, p=0.004). No significant differences in diagnostic yield were detected between "TBNA first" and "Cryobiopsy first" groups. We observed two cases of pneumothorax and one case of pneumomediastinum. CONCLUSIONS: Transbronchial cryobiopsy performed under EBUS guidance is a safe and useful approach that offers diagnostic histological samples of mediastinal lesions.

Transbronchial needle aspiration combined with cryobiopsy in the diagnosis of mediastinal diseases: a multicentre, open-label, randomised trial.

BACKGROUND: Transbronchial mediastinal cryobiopsy is a novel sampling technique for mediastinal disease. Despite the possibility of lung cancer misdiagnosis, the improved diagnostic yield of this approach for non-lung-cancer lesions compared with standard endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) highlights its diagnostic potential as a complementary technique to conventional biopsy. We aimed to evaluate the safety profile and added value of the combined use of transbronchial mediastinal cryobiopsy and standard EBUS-TBNA for the diagnosis of mediastinal diseases. METHODS: We conducted an open-label, randomised trial at three hospital sites in Europe and Asia. Eligible patients were aged 15 years or older, with at least one mediastinal lesion of 1 cm or longer in the short axis that required diagnostic bronchoscopy. Participants were randomly assigned (1:1) using a block randomisation scheme generated by a computer (block size of four participants based on a random table from an independent statistician) to the combined use of EBUS-TBNA and transbronchial mediastinal cryobiopsy (combined group) or EBUS-TBNA alone (control group). Because of the nature of the intervention, neither participants nor investigators were masked to group assignment. The coprimary outcomes were differences in procedure-related complications and diagnostic yield (defined as the proportion of participants for whom mediastinal biopsy led to a definitive diagnosis), assessed in the full analysis set, including all the patients who met the eligibility criteria and had a biopsy. A fully paired, intraindividual diagnostic analysis in participants who had both needle aspiration and mediastinal cryobiopsy was conducted, in addition to interindividual comparisons. This trial is now complete and is registered with ClinicalTrials.gov, NCT04572984. FINDINGS: Between Oct 12, 2020, and Sept 9, 2021, 297 consecutive patients were assessed for eligibility and 271 were enrolled and randomly assigned to the combined group (n=136) or the control group (n=135). The addition of cryobiopsy to standard sampling significantly increased the overall diagnostic yield for mediastinal lesions, as shown by both interindividual (126 [93%] of 136 participants in the combined group vs 109 [81%] of 135 in the control group; risk ratio [RR] 1·15 [95% CI 1·04-1·26]; p=0·0039) and intraindividual (126 [94%] of 134 vs 110 [82%] of 134; RR 1·15 [95% CI 1·05-1·25]; p=0·0026) analyses. In subgroup analyses in the intraindividual population, diagnostic yields were similar for mediastinal metastasis (68 [99%] of 69 participants in the combined group vs 68 [99%] of 69 in the control group; RR 1·00 [95% CI 0·96-1·04]; p=1·00), whereas the combined approach was more sensitive than standard needle aspiration in benign disorders (45 [94%] of 48 vs 32 [67%] of 48; RR 1·41 [95% CI 1·14-1·74]; p=0·0009). The combined approach also resulted in an improved suitability of tissue samples for molecular and immunological analyses of non-small-cell lung cancer. The incidence of adverse events related to the biopsy procedure did not differ between trial groups, as grade 3-4 airway bleeding occurred in three (2%) patients in the combined group and two (1%) in the control group (RR 0·67 [95% CI 0·11-3·96]; p=1·00). There were no severe complications causing death or disability. INTERPRETATION: The addition of mediastinal cryobiopsy to standard EBUS-TBNA resulted in a significant improvement in diagnostic yield for mediastinal lesions, with a good safety profile. These data suggest that this combined approach is a valid first-line diagnostic tool for mediastinal diseases. FUNDING: National Natural Science Foundation of China.

TWIST1 induces phenotypic switching of vascular smooth muscle cells by downregulating p68 and microRNA-143/145.

TWIST1 is an important basic helix-loop-helix protein linked to multiple physiological and pathological processes. Although TWIST1 is believed to be involved in vascular pathogenesis, its effects on homeostasis of smooth muscle cells (SMCs) remain poorly understood. Here, we show that TWIST1 protein levels were significantly elevated during SMC phenotypic switching in vivo and in vitro. TWIST1 overexpression promoted phenotypic switching of SMCs, while siRNA targeting of TWIST1 prevented cell transition. Mechanistically, TWIST1 decreased the level of microRNA-143/145, which governs smooth muscle marker gene transcription. In addition, TWIST1 repressed p68 mRNA and protein expression, a crucial modulator of SMC behavior and microRNA biogenesis. Our co-immunoprecipitation assay demonstrated a previously unrecognized molecular interaction between TWIST1 and p68 protein. Finally, we found that TWIST1 triggered SMC phenotypic switching and suppressed microRNA-143/145 expression by promoting the proteasomal degradation of p68. These data suggest a novel role of TWIST1 in the regulation of SMC homeostasis by modulating p68/microRNA-143/145 axis.

[Semi-synthesis of derivatives with C-3' and C-4' trans-configuration from (+)-praeruptorin A].

AIM: In order to compare the calcium antagonist activity between the derivatives of (+)-praeruptorin A with C-3' and C-4' cis-configuration and trans-configuration, and to look for new active compounds, some derivatives with C-3', C-4' trans-configuration of (+)-praeruptorin A were semi-synthsized. METHODS: (+)-Praeruptorin A was isolated from the root of Peucedanum praeruptorum. Basic hydrolysis of (+)-praeruptorin A was carried out. From the alkaline hydrolysis product (2), eight new products (5-12) with C-3', C-4' trans-configuration were semi-synthsized whose C-3' was linked to angeloyloxy and C-4' was linked to various acyloxy, using respective acids as acylating agents, DCC as a dehydrant, DMAP as catalyst. From the alkaline hydrolysis product (4), five new products (13-17) with C-3', C-4' trans-configuration were obtained whose C-3', C-4' is linked to various same acyloxys, using respective acids as acylating agents, DCC as dehydrant, DMAP as catalyst. Also from the alkaline hydrolysis product (4), using respective acyl chlorides as acylating agents, anhydrous dichloromethane containing minor pyridine as a solvent, the improved Schotten-Baumann reactions were carried out, two new products (18, 20) with C-3', C-4' trans-configuration were obtained whose only C-3' linked to acyloxy and two other new products (19, 21) with C-3', C-4' trans-configuration were obtained whose C-3' and C-4' linked two acyloxys. The structures of all the products were elucidated by spectral analyses including IR, 1HNMR and EIMS. The calcium antagonist activity of all of the products were tested by inhibition of the systole of rat artery ring. RESULTS: Seventeen compounds with C-3', C-4' trans-configuration were semi-synthesized from (+)-praeruptorin A for the first time and their calcium antagonist activity were evaluated. CONCLUSION: All of the derivatives were new compounds. Bioactivity assay indicated that some new compounds with C-3', C-4' trans-configuration showed obvious calcium antagonist activity, but they are not as strong as (+)-praeruptorin A. The activity of some products was shown to be similar to that of the derivatives with C-3', C-4' cis-configuration for the first time.

[Studies on structure modification of (+)-praeruptorin A].

AIM: In order to look for new active compounds, the structure of (+)-praeruptorin A is modified. METHODS: (+)-Praeruptorin A was isolated from the root of Peucedanum praeruptorum, basic hydrolysis of (+)-praeruptorin A and acyled reactions of hydrolysis product of (+)-praeruptorin A were carried out. RESULTS: Eighteen compounds were semi-synthesized from (+)-praeruptorin A. CONCLUSION: Fourteen compounds (5-18) among them are new compounds. Preliminary bioactivity assay indicated that the new compounds show calcium antagonist activity, but they are not as strong as (+)-praeruptorin A.

Two compounds from Peucedanum dissolutum.

A new compound, 3'(R)-O-beta-D-glucopyranosyl-3',4'-dihydroxanthyletin (1), and a known compound, prim-O-glucosylcimifugin (2), were isolated from the roots of Peucedanum dissolutum. The structure of 1 was elucidated by spectral evidence and chemical reaction. The NMR signals of carbons and protons of 2 were assigned for the first time by analysis of (1)H-(1)H COSY, HMQC and HMBC spectra.

Cytotoxic diterpenoids from Euphorbia pekinensis.

A new diterpenoid, named euphpekinensin, along with three known diterpenoids, was isolated from the roots of Euphorbia pekinensis for the first time and the structures were elucidated by spectral analysis. The 2D-NMR techniques such as 1H-1H COSY, HMQC, HMBC and NOESY spectra were mainly applied to determine the structure of the new diterpenoid. The four diterpenoids showed cytotoxic activity against human KB cells in vitro.