[New 2023 global definition of acute respiratory distress syndrome: progress and limitation].

Acute respiratory distress syndrome (ARDS) presents a challenge in clinical diagnosis as it lacks a definitive gold standard. Over the past 55 years, there have been several revisions to the definition of ARDS. With the progress of clinical practice and scientific research, the limitations of the "Berlin definition" have become increasingly evident. In response to these changes, the 2023 global definition of ARDS aims to address these issues by expanding the diagnostic targets, chest imaging, and methods for assessing hypoxia. Additionally, the new definition increases the diagnostic criteria to accommodate resource-constrained settings. The expansion facilitates early identification and treatment interventions for ARDS, thereby advancing epidemiological and clinically related research. Nevertheless, the broad nature of this revision may include patients who do not actually have ARDS, thus raising the risk of false-positive diagnoses. Therefore, additional verification is crucial to ascertain the validity and accuracy of the 2023 global definition of ARDS.

[Evaluation and clinical significance of gas exchange in patients with acute respiratory distress syndrome].

Gas exchange abnormalities is the pathophysiology characteristic of acute respiratory distress syndrome (ARDS). The severity of gas exchange abnormalities not only reflect the severity and outcome of the disease, but could also be an important index to guide individual mechanical ventilation settings and evaluate the therapeutic effects of inhaled vasodilator. The common techniques to measure gas exchange include multiple inert gas elimination technique, automatic lung parameter estimator, electrical impedance tomography, and single-photon emission CT. Nowadays, bedside techniques and measurements for improving gas exchange function in ARDS patients are still limited. Therefore, the improvement and promotion of bedside real-time gas exchange monitoring technology may achieve the goal of personalized medicine in ARDS. This article reviewed the common evaluation methods of gas exchange function in ARDS and their significance, in order to pay more attention to the evaluation of gas exchange function and further improve the prognosis of patients with ARDS.

[The effects of positive end-expiratory pressure on central venous pressure in patients with different chest wall elastic resistance].

Objective: To investigate the role of chest wall elastic resistance in determining the effects of positive end-expiratory pressure (PEEP) on central venous pressure (CVP) in patients with mechanical ventilation (MV). Methods: In this prospective study, according to the median of ratio of chest wall elastic resistance to respiratory system elastic resistance (Ers), patients were divided into high chest wall elastic resistance group (Ecw/Ers≥0.24) and low chest wall elastic resistance group [elastance of chest wall (Ecw)/Ers<0.24]. PEEP was set at 5, 10, 15 cmH2O (1 cmH2O=0.098 kPa) respectively. Clinical data including CVP, heart rate (HR), blood pressure (BP) and respiratory mechanics were recorded. Results: Seventy patients receiving MV were included from November 2017 to December 2018. Clinical characteristics including age, BP, HR, baseline PEEP, the ratio of arterial oxygen partial pressure to fractional inspired oxygen (P/F) and comorbidities were comparable in two groups. However, patients with high Ecw/Ers ratio presented higher body mass index (BMI) than those with low Ecw/Ers ratio[ (25.4±3.2) kg/m2 vs. (23.4±3.2) kg/m2, P=0.011]. As PEEP increased from 5 cmH2O to 10 cmH2O, CVP in high Ecw/Ers group increased significantly compared with that in low Ecw/Ers group [1.75(1.00, 2.13) mmHg (1 mmHg=0.133kPa) vs. 1.50(0.50, 2.00)mmHg,P=0.038], which was the same as PEEP increased from 10 cmH2O to 15 cmH2O [2.00(1.50, 3.00)mmHg vs. 1.50(1.00, 2.00)mmHg,P=0.041] or PEEP increased from 5 cmH2O to 15 cmH2O [ 3.75(3.00,4.63)mmHg vs. 3.00(1.63, 4.00)mmHg, P=0.012]. When PEEP increased from 5 cmH2O to 10 cmH2O, 10 cmH2O to 15 cmH2O and 10 cmH2O to 15 cmH2O, there were significant correlations between Ecw/Ers and CVP elevation (r=0.29, P=0.016; r=0.31, P=0.011; r=0.31, P=0.01 respectively). Conclusions: In patients receiving mechanical ventilation, elevation of PEEP leads to a synchronous change of CVP, which is corelated with patients' chest wall elastic resistances.

[Adherence to adjuvant with therapy imatinib in patients with gastrointestinal stromal tumor: a national multi-center cross-sectional study].

Objective: To analyze the current adherence to imatinib in patients with gastrointestinal stromal tumors (GIST) in China and its influencing factors. Methods: A cross-sectional survey was conducted. Study period: from October 1, 2020 to November 31, 2020. Study subjects: GIST patients taking imatinib who were diagnosed and treated in public tertiary level A general hospitals or oncology hospitals; those who had not been pathologically diagnosed, those who never received imatinib, or those who had taken imatinib in the past but stopped afterwards were excluded. The Questionnaire Star online surgery platform was used to design a questionnaire about the adherence to adjuvant imatinib therapy of Chinese GIST patients. The link of questionnaire was sent through WeChat. The questionnaire contained basic information of patients, medication status and Morisky Medication Adherence Scale. Results: A total of 2162 questionnaires from 31 provinces, autonomous regions, and municipalities were collected, of which 2005 were valid questionnaires, with an effective rate of 92.7%. The survey subjects included 1104 males and 901 females, with a median age of 56 (22-91) years old. Working status: 609 cases (30.4%) in the work unit, 729 cases (36.4%) of retirement, 667 cases of flexible employment or unemployment (33.3%). Education level: 477 cases (23.8%) with bachelor degree or above, 658 cases (32.8%) of high school, 782 cases (39.0%) of elementary or junior high school, 88 cases (4.4%) without education. Marital status: 1789 cases (89.2%) were married, 179 cases (8.9%) divorced or widowed, 37 cases (1.8%) unmarried. Two hundred and ninety-four patients (14.7%) had metastasis when they were first diagnosed, including 203 liver metastases, 52 peritoneal metastases, and 39 other metastases. One thousand eight hundred and sixty-nine patients underwent surgical treatment, of whom 1642 (81.9%) achieved complete resection. The median time of taking imatinib was 25 (1-200) months. Common adverse reactions of imatinib included 1701 cases (84.8%) of periorbital edema, 1031 cases (51.4%) of leukopenia, 948 cases (47.3%) of fatigue, 781 cases (39.0%) of nausea and vomiting, 709 cases (35.4%) of rash, and 670 cases (33.4%) of lower extremity edema. The score of the Morisky Medication Adherence Scale showed that 392 cases (19.6%) had poor adherence, 1023 cases (51.0%) had moderate adherence, and 590 cases (29.4%) had good adherence. Univariate analysis showed that gender, age, work status, economic income, residence, education level, marriage, the duration of taking medication and adverse reactions were associated with adherence to adjuvant imatinib therapy (all P<0.05). Multivariate analysis showed that female (OR=1.264, P=0.009), non-retirement (OR=1.454, P=0.001), monthly income ≤4000 yuan (OR=1.280, P=0.036), township residents (OR=1.332, P=0.005), unmarried or divorced or widowed (OR=1.362, P=0.026), the duration of imatinib medication >36 months (OR=1.478, P<0.001) and adverse reactions (OR=1.719, P=0.048) were independent risk factors for poor adherence to adjuvant imatinib. Among patients undergoing complete resection, 324 (19.7%) had poor adherence, 836 (50.9%) had moderate adherence, and 482 (29.4%) had good adherence. Meanwhile, 55 patients with good adherence (11.4%) developed recurrence after surgery, 121 patients with moderate adherence (14.5%) developed recurrence, 61 patients with poor adherence (18.8%) developed recurrence, and the difference was statistically significant (P=0.017). Conclusions: The adherence to adjuvant therapy with imatinib in Chinese GIST patients is relatively poor. Females, non-retirement, monthly income ≤4000 yuan, township residents, unmarried or divorced or widowed, the duration of imatinib medication >36 months, and adverse reactions are independently associated with poor adherence of GIST patients. Those with poor adherence have a higher risk of recurrence after surgery. Positive interventions based on the above risk factors are advocated to improve the prognosis of patients with GIST.

Inhibition of p53/p21 by TWIST alleviates TNF-α induced nucleus pulposus cell senescence in vitro.

OBJECTIVE: This study aims to reveal the TWIST protein expression in the degenerated nucleus pulposus (NP), its effect on the TNF-α treated NP cells, and to explore its specific mechanism of anti-senescence. PATIENTS AND METHODS: NP tissues from spine fracture patients without intervertebral disc degeneration (IDD) and the IDD patients were collected to detect the TWIST1/2 protein expression by Western blot (WB). NP cells isolated from the healthy tissue was treated with TNF-α to induce senescence, and the TWIST1/2 protein expression was also analyzed. We transfected NP cells with the plasmid coding TWIST to upregulate its expression, which was also cultured in the TNF-α condition. Besides, the TNF-α pretreated NP cells were further stimulated with the recombinant human TWIST1/2 protein. The collagen II and senescent marker ß-galactosidase (ß-gal) were determined by immunofluorescence (IF); the MMP-13, TIMP-3, IL-10, IL-1ß mRNA expression level was detected by quantitative Real Time PCR; the cell proliferation was analyzed by CCK8 assay; the cell cycle was measured by flow cytometry. RESULTS: TWIST1/2 protein was decreased both in the degenerated NP tissue, and TNF-α treated NP cells. The overexpression of TWIST1/2 could prevent the p53, p21, ß-gal, MMP-13, and IL-1ß expression, moreover, it protected the collagen II, TIMP-3, and IL-10 expression in the TNF-α treated NP cells. Additionally, TWIST overexpression also promoted cell proliferation by ensuring the process of the cell cycle. Furthermore, the supplement of TWIST protein was functional to reverse these senescent phenotypes caused by TNF-α partly. CONCLUSIONS: TWIST alleviates the TNF-αinduced NP cells senescence via the inhibition of the p53/p21 pathway.

[Past and present of risk stratification of gastrointestinal stromal tumors and its clinical value].

Gastrointestinal stromal tumor (GIST) is the most common soft tissue sarcoma in the gastrointestinal tract. Biological behavior of GIST is varied. It is very important to accurately assess the risk of recurrence and metastasis after resection of primary tumor in order to guide adjuvant therapy and predict prognosis. With increasing understanding of the biological behavior of GIST, the risk stratification criterion has undergone continuous reform and improvement since its introduction. In the early stage, clinical parameters such as tumor size and mitotic rate were formulated as risk stages, and then tumor site, tumor rupture and other factors were included to form a more accurate AFIP standard and modified NIH risk stratification. Recently, more researches have used new statistical methods such as nomogram and contour maps, which more accurately predict risk of recurrence and better guide adjuvant treatment. Thus, individualized treatment of GIST becomes possible.

[Therapy of coronavirus disease 2019 induced acute respiratory distress syndrome is different from traditional acute respiratory distress syndrome].

Coronavirus disease 2019 (COVID-19) has become a global public health emergency threatening people's lives around the world. Although the acute respiratory distress syndrome (ARDS) induced by COVID-19 is similar to the ARDS caused by other diseases in terms of pathophysiological basis and clinical manifestations, they are also different in many aspects, which lead to different clinical therapies. Therefore, understanding the differences and similarities of ARDS induced by COVID-19 and other diseases currently are the basis for clinicians to make decisions for the treatment of COVID-19 induced ARDS.

[The keypoints in treatment of the critical coronavirus disease 2019 patient(2)].

The treatment of critically ill patients with coronavirus disease 2019(COVID-19) faces compelling challenges. In this issue, we'd like to share our first-line treatment experience in treating COVID-19. Hemodynamics need be closely monitored and different types of shock should be distinguished. Vasoconstrictor drugs should be used rationally and alerting of complications is of the same importance. The risk of venous thromboembolism (VTE) needs to be assessed, and effective prevention should be carried out for high-risk patients. It is necessary to consider the possibility of pulmonary thromboembolism (PTE) in patients with sudden onset of oxygenation deterioration, respiratory distress, reduced blood pressure. However, comprehensive analysis of disease state should be taken into the interpretation of abnormally elevated D-Dimer. Nutritional support is the basis of treatment. It's important to establish individual therapy regimens and to evaluate, monitor and adjust dynamically. Under the current epidemic situation, convalescent plasma can only be used empirically, indications need to be strictly screened, the blood transfusion process should be closely monitored and the curative effect should be dynamically evaluated.

The long non-coding RNA PVT1/miR-145-5p/ITGB8 axis regulates cell proliferation, apoptosis, migration and invasion in non-small cell lung cancer cells.

Lung cancer is one of the leading causes of death worldwide and non-small cell lung cancer (NSCLC) accounts for approximately 80% of lung cancer. Long noncoding RNAs (lncRNAs) are closely associated with the development and progression of various cancers, including lung cancer. The purpose of this study was to explore the potential role and molecular mechanism of lncRNA plasmacytoma variant translocation 1 (PVT1) in regulating the proliferation, apoptosis, migration, and invasion of NSCLC cells. The expressions of PVT1, integrin ß-8 (ITGB8), and miR-145-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of ITGB8, MEK, p-MEK, ERK, and p-ERK were measured by western blot analysis. Cell proliferation, apoptosis, migration, and invasion were determined by MTT assay, flow cytometry, and transwell assay, respectively. The potential binding sites between miR-145-5p and PVT1 or ITGB8 were predicted by online software and verified by luciferase reporter assay. A xenograft tumor model was established to confirm the effect of PVT1 on NSCLC in vivo. We found out that the expression levels of PVT1 and ITGB8 were upregulated in NSCLC tissues and cells. Knockdown of PVT1 or ITGB8 suppressed cell proliferation, migration, invasion and promoted apoptosis in NSCLC cells, which could be reversed by ITGB8 overexpression in NSCLC cells. Moreover, PVT1 could regulate ITGB8 expression via direct binding to miR-145-5p. Furthermore, PVT1 regulated the MEK/ERK pathway by affecting ITGB8 expression. In addition, knockdown of PVT1 inhibited tumor growth, ITGB8 expression, MEK/ERK signaling pathway, and increased miR-145-5p expression in vivo. In conclusion, the knockdown of PVT1 inhibited proliferation, migration, and invasion but induced apoptosis of NSCLC cells by regulating miR-145-5p/ITGB8 axis and inhibiting MEK/ERK signaling pathway, providing a novel avenue for the treatment of NSCLC.

[Pharmacotherapeutics for the new coronavirus pneumonia].

The new coronavirus pneumonia (NCP), also named as COVID-19 by WHO on Feb 11 2020, is now causing a severe public health emergency in China since. The number of diagnosed cases is more than 40,000 until the submission of this manuscript. Coronavirus has caused several epidemic situations world widely, but the present contagious disease caused by 2019 new coronavirus is unprecedentedly fulminating. The published cohorts of 2019 new coronavirus (n-Cov) are single-center studies, or retrospective studies. We here share the therapeutic experiences of NCP treatment with literature review. Combination of Ribavirin and interferon-α is recommended by the 5(th) edition National Health Commission's Regimen (Revised Edition) because of the effect on Middle East respiratory syndrome (MERS), and the effectiveness of Lopinavir/Ritonavir and Remdisivir needs to be confirmed by randomized controlled trial (RCT), given the situation of no specific antivirus drug on NCP is unavailable. Systemic glucocorticosteroid is recommended as a short term use (1~2 mg·kg(-1)·d(-1), 3~5 d) by the 5(th) edition National Health Commission's Regimen (Revised Edition) yet RCTs are expected to confirm the effectiveness. Inappropriate application of antibiotics should be avoided, especially the combination of broad-spectrum antibiotics, for the NCP is not often complicated with bacterial infection.

[Pharmacotherapeutics for the New Coronavirus Pneumonia].

The New Coronavirus Pneumonia (NCP, also named as COVID-19 by WHO on Feb 11 2020, is now causing a severe public health emergency in China since. The number of diagnosed cases is more than 40,000 until the submission of this manuscript. Coronavirus has caused several epidemic situations world widely, but the present contagious disease caused by 2019 new Coronavirus is unprecedentedly fulminating. The published cohorts of 2019 new Coronavirus (n-Cov) are single-center studies, or retrospective studies. We here share the therapeutic experiences of NCP treatment with literature review. Combination of Ribavirin and Interferon-α is recommended by the 5(th) edition National Health Commission's Regimen (Revised Edition) because of the effect on MERS (Middle East Respiratory Syndrome), and the effectiveness of Lopinavir/Ritonavir and Remdisivir needs to be confirmed by randomized controlled trial (RCT), given the situation of no specific antivirus drug on NCP is unavailable. Systemic glucocorticosteroid is recommended as a short term use (1~2 mg.kg(-1).d(-1), 3~5d ) by the 5(th) edition National Health Commission's Regimen (Revised Edition) yet RCTs are expected to confirm the effectiveness. Inappropriate application of antibiotics should be avoided, especially the combination of broad-spectrum antibiotics, for the NCP is not often complicated with bacterial infection.

[The keypoints in treatment of the critical coronavirus disease 2019 patient(1)].

COVID-19 has been prevalent in Wuhan and spread rapidly to all of our country. Some cases can develop into ARDS, or even death. We will share the treatment experience of severe COVID-19 with the first-line treatment experience. The best respiratory support mode should be selected, but the timing of intubation and protection during intubation are two difficulties; patients with high level peep and poor effect in prone position can be given ECMO support. For COVID-19 patients with mechanical ventilation, reasonable sedation and analgesia strategies should be formulated; delirium should not be ignored. In addition, there is up regulation of inflammatory factors in patients with severe COVID-19, but the effect of renal replacement therapy needs to be further confirmed by clinical research.

Downregulation of long non-coding RNA XIST inhibits cell proliferation, migration, invasion and EMT by regulating miR-212-3p/CBLL1 axis in non-small cell lung cancer cells.

OBJECTIVE: Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors in the world and its 5-year survival rate is very low. Long non-coding RNA X-inactive specific transcript (lncRNA XIST) has been demonstrated to play vital roles in NSCLC, but the exact molecular mechanisms underlying NSCLC still need to be further explored. PATIENTS AND METHODS: Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) was performed to detect the expression of XIST, miR-212-3p and Casitas B-lineage proto-oncogene like 1 (CBLL1). Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to analyze the relationship among XIST, miR-212-3p and CBLL1. Cell Counting Kit-8 (CCK-8) assay and transwell invasion assay were carried out to evaluate cell proliferation, migration and invasion, respectively. Western blot analysis was conducted to examine the protein expression of CBLL1, E-cadherin, N-cadherin and Vimentin. Murine xenograft assay was conducted to explore the role of XIST in vivo. RESULTS: Expression levels of XIST and CBLL1 were markedly upregulated, while the miR-212-3p level was markedly downregulated in NSCLC tissues and cells. MiR-212-3p was identified as a direct target of XIST, and miR-212-3p was predicted to target CBLL1. XIST knockdown repressed NSCLC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in vitro, and suppressed tumor growth in vivo, while miR-212-3p inhibition restored the effects. Furthermore, CBLL1 overexpression could abolish the effects of miR-212-3p overexpression on NSCLC cell proliferation, migration, invasion and EMT in vitro. CONCLUSIONS: XIST was significantly decreased in NSCLC tissues and cells, and XIST knockdown suppressed the proliferation, migration, invasion and EMT of NSCLC cells by miR-212-3p/CBLL1 axis. These findings facilitated our understanding of lncRNA regulation in NSCLC.