The impact of delayed tracheostomy on critically ill patients receiving mechanical ventilation: a retrospective cohort study in a chinese tertiary hospital.

OBJECTIVES: The timing of tracheostomy for critically ill patients on mechanical ventilation (MV) is a topic of controversy. Our objective was to determine the most suitable timing for tracheostomy in patients undergoing MV. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: One thousand eight hundred eighty-four hospitalisations received tracheostomy from January 2011 to December 2020 in a Chinese tertiary hospital. METHODS: Tracheostomy timing was divided into three groups: early tracheostomy (ET), intermediate tracheostomy (IMT), and late tracheostomy (LT), based on the duration from tracheal intubation to tracheostomy. We established two criteria to classify the timing of tracheostomy for data analysis: Criteria I (ET ≤ 5 days, 5 days < IMT ≤ 10 days, LT > 10 days) and Criteria II (ET ≤ 7 days, 7 days < IMT ≤ 14 days, LT > 14 days). Parameters such as length of ICU stay, length of hospital stay, and duration of MV were used to evaluate outcomes. Additionally, the outcomes were categorized as good prognosis, poor prognosis, and death based on the manner of hospital discharge. Student's t-test, analysis of variance (ANOVA), Mann-Whitney U test, Kruskal-Wallis test, Chi-square test, and Fisher's exact test were employed as appropriate to assess differences in demographic data and individual characteristics among the ET, IMT, and LT groups. Univariate Cox regression model and multivariable Cox proportional hazards regression model were utilized to determine whether delaying tracheostomy would increase the risk of death. RESULTS: In both of two criterion, patients with delayed tracheostomies had longer hospital stays (p < 0.001), ICU stays (p < 0.001), total time receiving MV (p < 0.001), time receiving MV before tracheostomy (p < 0.001), time receiving MV after tracheostomy (p < 0.001), and sedation durations. Similar results were also found in sub-population diagnosed as trauma, neurogenic or digestive disorders. Multinomial Logistic regression identified LT was independently associated with poor prognosis, whereas ET conferred no clinical benefits compared with IMT. CONCLUSIONS: In a mixed ICU population, delayed tracheostomy prolonged ICU and hospital stays, sedation durations, and time receiving MV. Multinomial logistic regression analysis identified delayed tracheostomies as independently correlated with worse outcomes. TRIAL REGISTRATION: ChiCTR2100043905. Registered 05 March 2021. http://www.chictr.org.cn/listbycreater.aspx.

Targeting TFH cells is a novel approach for donor-specific antibody desensitization of allograft candidates: an in vitro and in vivo study.

The presence of donor-specific antibodies (DSA) are associated with graft failure either following human leukocyte antigen (HLA)-mismatched allogeneic stem cell transplantation or after organ transplantation. Although targeting B cells and plasma cells have been used for desensitization, there have been reports of failure. T-follicular helper (Tfh) cells assist B cells in differentiating into antibody-secreting plasma cells. We used haploidentical allograft as a platform to investigate the possibility of targeting Tfh cells to desensitize DSA. The quantities of circulating Tfh (cTfh) cell subsets in allograft candidates were abnormal, and these cells, including the cTfh2 and cTfhem cell subsets, were positively related to the production of anti-HLA antibodies. Ex vivo experiments showed that the cTfh cells of anti-HLA antibody-positive allograft candidates could induce B cells to differentiate into DSA-producing plasmablasts. The immune synapse could be involved in the assistance of cTfh cells to B cells in antibody production. In vitro experiments and in vivo clinical pilot studies indicated that targeting cTfh cells with sirolimus can inhibit their auxiliary function in assisting B cells. Ex vivo and in vivo studies demonstrated the effect of sirolimus and rituximab on DSA desensitization compared with either sirolimus or rituximab alone (60%, 43.75%, and 30%, respectively). Our findings provide new insight into the role of Tfh cells in the pathogenesis of DSA production in HLA-mismatched transplant candidates. Our data also indicate that targeting Tfh cells is a novel strategy for DSA desensitization and combination of sirolimus and rituximab might be a potential therapy. The prospective cohort of this study is registered at http://www.chictr.org.cn as #ChiCTR-OPC-15006672.

Anti-inflammatory effects of acupuncture in the treatment of chronic obstructive pulmonary disease.

Numerous randomised controlled trials have suggested the positive effects of acupuncture on chronic obstructive pulmonary disease (COPD). However, the underlying therapeutic mechanisms of acupuncture for COPD have not been clearly summarized yet. Inflammation is central to the development of COPD. In this review, we elucidate the effects and underlying mechanisms of acupuncture from an anti-inflammatory perspective based on animal studies. Cigarette smoke combined with lipopolysaccharide is often used to establish animal models of COPD. Electroacupuncture can be an effective intervention to improve inflammation in COPD, and Feishu (BL13) and Zusanli (ST36) can be used as basic acupoints in COPD animal models. Different acupuncture types can regulate different types of inflammatory cytokines; meanwhile, different acupuncture types and acupoint options have similar effects on modulating the level of inflammatory cytokines. In particular, acupuncture exerts anti-inflammatory effects by inhibiting the release of inflammatory cells, inflammasomes and inflammatory cytokines. The main underlying mechanism through which acupuncture improves inflammation in COPD is the modulation of relevant signalling pathways: nuclear factor-κB (NF-κB) (e.g., myeloid differentiation primary response 88/NF-κB, toll-like receptor-4/NF-κB, silent information regulator transcript-1/NF-κB), mitogen-activated protein kinase signalling pathways (extracellular signal-regulated kinase 1/2, p38 and c-Jun NH2-terminal kinase), cholinergic anti-inflammatory pathway, and dopamine D2 receptor pathway. The current synthesis will be beneficial for further research on the effect of acupuncture on COPD inflammation. Please cite this article as: Jiang LH, Li PJ, Wang YQ, Jiang ML, Han XY, Bao YD, Deng XL, Wu WB, Liu XD. Anti-inflammatory effects of acupuncture in the treatment of chronic obstructive pulmonary disease. J Integr Med. 2023; 21(6): 518-527.

Correction: miR-1260b, mediated by YY1, activates KIT signaling by targeting SOCS6 to regulate cell proliferation and apoptosis in NSCLC.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

miR-1260b, mediated by YY1, activates KIT signaling by targeting SOCS6 to regulate cell proliferation and apoptosis in NSCLC.

Non-small cell lung cancer (NSCLC) is one of the most common aggressive malignancies. miRNAs have been identified as important biomarkers and regulators of NSCLC. However, the functional contributions of miR-1260b to NSCLC cell proliferation and apoptosis have not been studied. In this study, miR-1260b was upregulated in NSCLC plasma, tissues, and cell lines, and its high expression was correlated with tumor size and progression. Functionally, miR-1260b overexpression promoted cell proliferation and cell cycle, conversely inhibited cell apoptosis and senescence. Mechanically, miR-1260b negatively regulated SOCS6 by directly binding to its 3'-UTR. Furthermore, miR-1260b-mediated suppression of SOCS6 activated KIT signaling. Moreover, YY1 was an upstream regulator of miR-1260b. This study is the first to illustrate that miR-1260b, mediated by YY1, activates KIT signaling by targeting SOCS6 to regulate NSCLC cell proliferation and apoptosis, and is a potential biomarker and therapeutic target for NSCLC. In sum, our work provides new insights into the molecular mechanisms of NSCLC involved in cell proliferation and apoptosis.

Three-dimensional navigation-guided thoracoscopic combined subsegmentectomy for intersegmental pulmonary nodules.

BACKGROUND: Extended or combined segmentectomies are usually adapted for intersegmental pulmonary nodules. This study explored precise combined subsegmentectomy (CSS) under the guidance of three-dimensional computed tomography bronchography and angiography (3D-CTBA). METHODS: The definition of a pulmonary intersegmental nodule was based on a minimum distance between the nodule and the involved intersegmental veins in the preoperative 3D-CTBA being less than the size of the nodule. Centering on the involved intersegmental vein, two adjacent subsegments belonging to the different segments were combined as a resected unit. RESULTS: We retrospectively reviewed the records of 47 patients (mean age 53.6 ± 12.3, range: 26-81 years) who underwent CSS. Thirty-nine (83.0%) nodules were involved in most intersegmental locations of the upper lobes; the remainder in the lower lobes. The mean nodule size was 0.86 ± 0.32 cm; the mean margin width was 2.20 ± 0.38 cm. Pathological stages included: Tis (8 cases), T1mi (16), IA1 (T1aN0M0, 13), and IA2 (T1bN0M0, 5). Pathological diagnoses included: invasive adenocarcinoma (18 cases), minimally invasive adenocarcinoma (16), adenocarcinoma in situ (8), atypical adenomatous hyperplasia (3), and benign (2). The average operative duration was 190.8 ± 54.9 minutes; operative hemorrhage was 42.7 ± 23.0 mL; 5.8 ± 2.8 lymph nodes dissected had not metastasized; the duration of postoperative chest tube drainage was 3.0 ± 1.8 days; and the postoperative hospital stay was 5.3 ± 2.4 days. CONCLUSIONS: Under 3D navigation, thoracoscopic CSS is a safe technique for intersegmental nodules, sparing more pulmonary parenchyma and ensuring safe margins to achieve anatomical resection.

Video-mediastinoscopy assisted fish bone extraction and superior Medistinal abscess debridement.

BACKGROUND: Mediastinum abscess caused by sharp esophageal foreign body perforation usually needs surgical treatment, and the surgical procedures vary according to size of perforation and scope of abscess, etc. For special case with small esophageal mucosal crevasse and focal abscess confined to mediastinum, minimally invasive surgery with guidance of video-mediastinoscopy would be an alternative method, however, application of video-mediastinoscopy in this life-threatening situation was rarely reported. CASE PRESENTATION: One patient with detention of fish bone stuck in the esophagus developed systemic inflammatory response syndrome. Computed tomography results revealed that two high-density foreign bodies migrated extraluminally and caused abscess confined in the mediastinum. Multidisplinary collaborative efforts of anesthesiology, gastroenterology and thoracic surgery were made to optimize the therapeutic process. By taking advantages of wide working channel and better exposure of video-mediastinoscopy, two sharp fish bones were removed with minimal risk of injuring adjacent important tissues, furthermore, complete debridement of the abscess and precise drainage tube indwelling was achieved simultaneously. Postoperative comprehensive therapy including anti-infection and nutrition support guaranteed a smooth transition of perioperative period. CONCLUSION: This is the first report on application of video-mediastinoscopy in removing two fish bones that migrated extraluminally and debridement of the abscess caused by esophagus perforation with minimal injury risk, which offer a safe and effective minimal invasive method for specific cases.

Placenta-specific protein 1 promotes cell proliferation and invasion in non-small cell lung cancer.

Pulmonary carcinoma-associated proteins have emerged as crucial players in governing fundamental biological processes such as cell proliferation, apoptosis and metastasis in human cancers. Placenta-specific protein 1 (PLAC1) is a cancer-related protein, which is activated and upregulated in a variety of malignant tissues, including prostate cancer, gastric adenocarcinoma, colorectal, epithelial ovarian and breast cancer. However, its biological role and clinical significance in non-small cell lung cancer (NSCLC) development and progression are still unknown. In the present study, we found that PLAC1 was significantly upregulated in NSCLC tissues, and its expression level was associated with advanced pathological stage and it was also correlated with shorter progression-free survival of lung cancer patients. Furthermore, knockdown of PLAC1 expression by siRNA inhibited cell proliferation, induced apoptosis and impaired invasive ability in NSCLC cells partly via regulation of epithelial-mesenchymal transition (EMT)-related protein expression. Our findings present that increased PLAC1 could be identified as a negative prognostic biomarker in NSCLC and regulate cell proliferation and invasion. Thus, we conclusively demonstrated that PLAC1 plays a key role in NSCLC development and progression, which may provide novel insights on the function of tumor-related gene-driven tumorigenesis.

Thoracoscopic Pulmonary Sub-Subsegmentectomy Based on Three-Dimensional Images.

Thoracoscopic anatomic pulmonary segmentectomy and subsegmentectomy have become sophisticated surgical solutions for complex pulmonary diseases. The rapid development of three-dimensional computed tomographic angiography (3DCTA) has made it possible to provide more refined individualized anatomic details and has consequently enabled subsubsegmentectomy (SSS). In this study, we report two successful thoracoscopic anatomic SSSs of the left S1+2aii and S3aii under the guidance of 3DCTA reconstructed images. To the best of our knowledge, these are the first two cases of SSSs ever detailed reported. The nomenclature of subsubsegments is adopted according to the Japanese Committee on the Nomenclature for Bronchial Branching.

Three-dimensional computed tomography bronchography and angiography in the preoperative evaluation of thoracoscopic segmentectomy and subsegmentectomy.

Thoracoscopic pulmonary segmentectomy is technically meticulous due to the complicated anatomical variations of segmental bronchus and vessels. Currently three dimensional-computed tomography angiography (3D-CTA) could only meet the simple requirements of segmentectomy. Our center developed a software for reconstruction, "deepinsight", which could effectively solve some key technical problems. Preoperative three-dimensional computed tomography bronchography and angiography (3D-CTBA) could reveal the anatomical structures and improve the accuracy of operation. Preoperative simulation on the three-dimensional image is helpful for surgery planning, which includes nodule location, identification of the targeted vessels, bronchus and surgical margin, revealing of anatomical variations, and planning of surgical approach. With the assistance of 3D navigation, during the surgical procedure all the targeted structures could be divided accurately, the intersegmental veins could be preserved, the targeted parenchyma could be en bloc removed, and the surgical margin could be ensured. Our center has developed a method to separate pulmonary segments from the lobe based on cone-shaped principle, and we named it "Cone-shaped Segmentectomy". This technique covers precise identification and dissection of segmental bronchus, vessels and intersegmental demarcation, which ultimately achieve a completely anatomical segmentectomy.

Thoracoscopic right posterior segmentectomy of a patient with anomalous bronchus and pulmonary vein.

A 39-year-old woman was admitted to our hospital for a pure ground-glass opacity that had been detected in the right lung during a regular examination. A computed tomography scan showed a pure ground-glass opacity beneath the pleura of the right upper lobe of the lung that had enlarged over time. As a consequence, a lung adenocarcinoma was suspected. Meanwhile, three-dimensional computed tomography scans revealed a tracheal bronchus originating directly from the lateral wall of the trachea. The patient consequently underwent posterior segmental resection and mediastinal lymph node sampling by video-assisted thoracic surgery. During surgery, in addition to the tracheal bronchus, a variable central vein was found entering the left atrium dorsal to the right pulmonary artery trunk. We submit that, to the best of our knowledge, this is the first case of its kind ever reported.

Efficacy of 3 years of adefovir monotherapy in chronic hepatitis B patients with lamivudine resistance.

AIM: To study the effect of rescue monotherapy with adefovir (ADV) in patients with chronic hepatitis B (CHB) who developed drug resistance to lamivudine (LAM). METHODS: A total of 76 treated CHB patients with resistance to LAM were enrolled in the present study. The patients' baseline characteristics, such as age, gender, blood tests and hepatitis B virus (HBV) DNA were collected; therapy duration and the response of each patient were also recorded. ADV monotherapy was set as the observation group A. Twenty-four patients with LAM resistance, who were set as group B, accepted combined therapy with LAM + ADV. Patients were followed up at 0, 12, 24, 52, 104 and 156 wk. Hepatitis B surface antigen status, hepatitis B e antigen (HBeAg)/anti-HBe status, HBV DNA level and biochemical indexes were monitored. Sequencer of HBV polymerase gene was performed on the ABI 3730 automated sequencer. If no desired effects had been achieved during the course of treatment, patients' choices were also taken into account. The control group was tested at the same time. RESULTS: In the two groups, 27 cases developed viral breakthrough after LAM treatment response. The remaining 49 cases underwent biochemical rebound accompanied by rtM204I/V or rtL180M mutation. In group A, 52 cases finished 156 wk of ADV monotherapy; of whom, 36 cases were HBeAg positive and 16 HBeAg negative. In patients whose baseline HBV DNAs were 10(3)-10(5) copies/mL, 88.8% of patients' HBV DNAs were lower than the lower test limit (10(3) copies/mL) after 12 to 156 wk of ADV treatment. In patients whose baseline HBV DNAs were ≥ 10(6) copies/mL, 41.1%-47.0% of patients' HBV DNAs were lower than the lower test limit after the same course of ADV therapy (χ(2) were 4.35-5.4, 41.1%-47.0% vs 88.8% group 10(3)-10(5) copies/mL, P < 0.01). In group A, seroconversion of HBeAg developed in 8 of 36 cases (22.2%). In group B, 24 cases finished 156 wk of LAM + ADV; of whom, 17 cases were HBeAg positive and 7 HBeAg negative. In patients whose baseline HBV DNAs were 10(3)-10(5) copies /mL, 81.8% of patients' HBV DNAs were lower than the lower test limit (10(3) copies/mL) after 12 to 156 wk of treatment. In the patients whose baseline HBV DNAs were ≥ 10(6) copies/mL, 46.1%-53.8% of patients' HBV DNAs were lower than the lower test limit after the same course of LAM + ADV therapy (χ(2) were 4.1-5.0, 46.1%-53.8% vs 81.8% group 10(3)-10(5) copies/mL, P < 0.05-0.01). In group B, 4 of 17 cases (23.5%) developed seroconversion of HBeAg. Treatment outcomes in groups A and B were comparable. CONCLUSION: In both group A and B, the ratios of virological response have similar efficacy in patients with lower baseline HBV DNAs.

Degradable nanogels as a nanoreactor for growing silica colloids.

Degradable nanogels with cleavable disulfide bonds were designed and used as a catalytic template, providing an alkali microenvironment. Well-defined hybrid silica colloids could be obtained by hydrolyzing tetraethyl orthosilicate (TEOS) in the nanogels. The size of silica colloids was found to be dependent on the size of the nanogels. After the removal of nanogels through reduction with 1,4-dithiothreitol (DTT), mesoporous silica colloids with a rough surface were obtained. The mesoporous structure of the colloids after reduction was characterized by transmission electron microscopy (TEM), surface area analysis, and X-ray diffraction (XRD). This work also provides an effective route for the preparation of mesoporous silica nanostructures, which may find wide applications as catalyst templates and drug carriers.

1-Benzyl-2,3-dihydro-quinolin-4(1H)-one.

In the title compound, C(16)H(15)NO, the two aromatic rings are approximately perpendicular; the carbonyl group is twisted out of the adjacent benzene ring by 14.8 (2)°. In the heterocyclic ring, the C atom linked to the carbonyl group and the C atom linked to the N atom have opposite deviations of 0.467 (5) and 0.184 (4) Å, respectively, from the plane of the benzene ring. The N atom lies approximately in the plane of the phenyl ring. There are no conventional hydrogen bonds; the packing of mol-ecules in the crystal structure is stabilized by van der Waals forces.

[Stress analysis of separators with different specifications].

OBJECTIVE: To evaluate the shape and structure of different separators affecting the mechanical behavior. METHODS: The stress of different separators was analyzed by ANSYS software. Various separators were meshed into one-dimensional solid elements and the material character parameters were inputted. The loads were added gradually. RESULTS: The stress was related to the arm of force and the point of force application. CONCLUSIONS: The force applied can be controlled by selecting different separators.