Lung ultrasound score evaluation of the effect of pressure-controlled ventilation volume-guaranteed on patients undergoing laparoscopic-assisted radical gastrectomy.

BACKGROUND: Laparoscopic-assisted radical gastrectomy (LARG) is the standard treatment for early-stage gastric carcinoma (GC). However, the negative impact of this procedure on respiratory function requires the optimized intraoperative management of patients in terms of ventilation. AIM: To investigate the influence of pressure-controlled ventilation volume-guaranteed (PCV-VG) and volume-controlled ventilation (VCV) on blood gas analysis and pulmonary ventilation in patients undergoing LARG for GC based on the lung ultrasound score (LUS). METHODS: The study included 103 patients with GC undergoing LARG from May 2020 to May 2023, with 52 cases undergoing PCV-VG (research group) and 51 cases undergoing VCV (control group). LUS were recorded at the time of entering the operating room (T0), 20 minutes after anesthesia with endotracheal intubation (T1), 30 minutes after artificial pneumoperitoneum (PP) establishment (T2), and 15 minutes after endotracheal tube removal (T5). For blood gas analysis, arterial partial pressure of oxygen (PaO2) and partial pressure of carbon dioxide (PaCO2) were observed. Peak airway pressure (Ppeak), plateau pressure (Pplat), mean airway pressure (Pmean), and dynamic pulmonary compliance (Cdyn) were recorded at T1 and T2, 1 hour after PP establishment (T3), and at the end of the operation (T4). Postoperative pulmonary complications (PPCs) were recorded. Pre- and postoperative serum interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay. RESULTS: Compared with those at T0, the whole, anterior, lateral, posterior, upper, lower, left, and right lung LUS of the research group were significantly reduced at T1, T2, and T5; in the control group, the LUS of the whole and partial lung regions (posterior, lower, and right lung) decreased significantly at T2, while at T5, the LUS of the whole and some regions (lateral, lower, and left lung) increased significantly. In comparison with the control group, the whole and regional LUS of the research group were reduced at T1, T2, and T5, with an increase in PaO2, decrease in PaCO2, reduction in Ppeak at T1 to T4, increase in Pmean and Cdyn, and decrease in Pplat at T4, all significant. The research group showed a significantly lower incidence of PPCs than the control group within 3 days postoperatively. Postoperative IL-1ß, IL-6, and TNF-α significantly increased in both groups, with even higher levels in the control group. CONCLUSION: LUS can indicate intraoperative non-uniformity and postural changes in pulmonary ventilation under PCV-VG and VCV. Under the lung protective ventilation strategy, the PCV-VG mode more significantly improved intraoperative lung ventilation in patients undergoing LARG for GC and reduced lung injury-related cytokine production, thereby alleviating lung injury.

Integrative network-based analysis on multiple Gene Expression Omnibus datasets identifies novel immune molecular markers implicated in non-alcoholic steatohepatitis.

Introduction: Non-alcoholic steatohepatitis (NASH), an advanced subtype of non-alcoholic fatty liver disease (NAFLD), has becoming the most important aetiology for end-stage liver disease, such as cirrhosis and hepatocellular carcinoma. This study were designed to explore novel genes associated with NASH. Methods: Here, five independent Gene Expression Omnibus (GEO) datasets were combined into a single cohort and analyzed using network biology approaches. Results: 11 modules identified by weighted gene co-expression network analysis (WGCNA) showed significant association with the status of NASH. Further characterization of four gene modules of interest demonstrated that molecular pathology of NASH involves the upregulation of hub genes related to immune response, cholesterol and lipid metabolic process, extracellular matrix organization, and the downregulation of hub genes related to cellular amino acid catabolic, respectively. After DEGs enrichment analysis and module preservation analysis, the Turquoise module associated with immune response displayed a remarkably correlation with NASH status. Hub genes with high degree of connectivity in the module, including CD53, LCP1, LAPTM5, NCKAP1L, C3AR1, PLEK, FCER1G, HLA-DRA and SRGN were further verified in clinical samples and mouse model of NASH. Moreover, single-cell RNA-seq analysis showed that those key genes were expressed by distinct immune cells such as microphages, natural killer, dendritic, T and B cells. Finally, the potential transcription factors of Turquoise module were characterized, including NFKB1, STAT3, RFX5, ILF3, ELF1, SPI1, ETS1 and CEBPA, the expression of which increased with NASH progression. Discussion: In conclusion, our integrative analysis will contribute to the understanding of NASH and may enable the development of potential biomarkers for NASH therapy.

The Chinese Thoracic Oncology Group (CTONG) therapeutic option scoring system: a multiple-parameter framework to assess the value of lung cancer treatment options.

BACKGROUND: Currently, there is no standard context that conforms to the Chinese national framework for evaluating medical decisions regarding the treatment of lung cancer. METHODS: This draft was formulated after a systematic review and a focus group discussion among 20 experts, who were senior physicians with extensive clinical experience from the Chinese Thoracic Oncology Group (CTONG) task force. Subsequently, a draft and a five-point Likert scale were sent to 300 CTONG working group members. These were modified according to feedback from a four-round modified Delphi approach. Hence, the first version of the 'Therapeutic option of lung cancer: CTONG scoring system' was formulated. Afterward, a corresponding questionnaire was designed to collect opinions on the weight allocation of various indicators. This was issued through the WeChat platform, "Oncology News" application and e-mails from October 23, 2020, to November 25, 2020. Participants from numerous occupations in cancer-related fields from various regions of China were included in the study. Overall and subgroup analyses regarding weight allocations were performed. The differences between participant-allocated and reference weights were considered to adjust the framework. RESULTS: The framework contained four aspects and six indicators, including efficacy [progression-free survival (PFS)/overall survival (OS) and subsequent treatment], safety [treatment-related severe adverse event (SAE), dose adjustment], quality of life (Qol), and compensation. The reference weights were 50%, 5%, 10%, 5%, 10%, and 20% for each indicator. By November 25, 2020, 1,043 valid questionnaires had been obtained. The majority of the questionnaires were completed by physicians (86.5%). Subgroup analysis among the various groups showed an overall consistent trend. Besides, significant differences between the participant-allocated and reference weights were found among PFS/OS (difference: -11.5%), compensation (difference: -10.1%), and subsequent treatment (difference: 9.7%) indicators. After discussion, the final weight allocations were set at 45%, 10%, 15%, 5%, 10%, and 15% for PFS/OS, subsequent treatment, treatment-related SAE, dose adjustment, Qol, and compensation, respectively. CONCLUSIONS: The CTONG scoring system, as an objective evaluation model that involves multiple parameters, is a breakthrough method for evaluating the therapeutic value of lung cancer treatment options in China, which is worthy of further verification in future clinical practice.

The changing landscape of clinical trial and approval processes in China.

In the past decade, the standards of clinical trials in China have moved closer to international standards, thus encouraging the development of innovative drugs. However, a large backlog of pending applications for both drug approval and clinical trial registration has arisen owing to the complexity of the approval process, the volume of applications and a lack of staff available to process these applications, among other reasons. To improve the drug approval process, a 'four-colour-light' strategy was introduced. Different drugs are classified into redefined categories of innovative and generic drugs, with priority being given to approval decisions concerning innovative drugs. Other improvement strategies are now also being implemented, including the development of a new clinical trial approval system and several measures designed to encourage greater participation of Chinese researchers and research centres in international clinical trials. In this Perspective, the changing landscape of clinical approval in China is described, including the difficulties that drug approval authorities face in this rapidly developing nation and the novel strategies that are being used to find solutions.

Synthesis, Fungicidal Activity, and Structure Activity Relationship of ß-Acylaminocycloalkylsulfonamides against Botrytis cinerea.

In order to discover new antifungal agrochemicals that could have highly active and novel motifs, thirty-six new 2-acylaminocycloalkylsulfonamides (IV) were synthesized. Their structures were characterized and confirmed by 1H NMR, 13C NMR, IR, MS, elemental analysis and X-ray single crystal diffraction. In vitro and in vivo activities against various Botrytis cinerea strains were evaluated. Bioassay results revealed that most of the title compounds exhibited excellent in vitro fungicidal activity, in which compound IV-26 showed the highest activity against sensitive, low-resistant, moderate-resistant and high-resistant strains of B. cinerea compared with the positive fungicide procymidone. Meanwhile in vivo fungicidal activity of compound IV-31 was better than the commercial fungicides procymidone and chesulfamide in greenhouse trial. The structure activity relationship (SAR) was also discussed and the results were of importance to the structural optimization and development of more potent sulfonamides antifungal agents.

The efficacy and safety of arsenic trioxide with or without all-trans retinoic acid for the treatment of acute promyelocytic leukemia: a meta-analysis.

Arsenic trioxide (ATO) and all-trans-retinoic acid (ATRA) could induce apoptosis and differentiation in acute promyelocytic leukemia (APL) cells, respectively, thus the possibility of synergism between them was raised. This meta-analysis assessed the effectiveness and safety of ATO combined with ATRA in the treatment of APL. Compared with ATO alone, induction therapy with ATO/ATRA significantly increased the complete remission (CR) rate (RR: 1.08, 95% CI: 1.00-1.17, P=0.04), shortened the time to achieve CR (WMD: -6.51, 95% CI: -11.32 to -1.70, P=0.008), and improved the molecular remission rate after consolidation therapy (RR: 1.74, 95% CI: 1.14-2.66, P=0.01) and the 1-year disease-free survival rate (RR: 1.22, 95% CI: 1.00-1.50, P=0.05). There were no statistically significant differences between two treatments in terms of early death and main adverse events. These results suggested that ATO/ATRA could synergistically improve the overall outcome of newly diagnosed and relapsed APL patients, supporting the use of ATO/ATRA as an effective treatment for all APL patients previously untreated with ATO.