The Role of Zuo Jin Wan in Modulating the Tumor Microenvironment of Colorectal Cancer.

INTRODUCTION: Traditional Chinese medicine (TCM) can modulate the immune function of tumor patients in various ways. Zuojin Wan (ZJW, a 6:1 ratio of Huanglian and Wuzhuyu) can modulate the microenvironment of ulcerative colitis, but its role in regulating the CRC microenvironment remains unclear. Exploring the role of ZJW in CRC immunomodulation may improve the antitumor effect of existing immunotherapeutic strategies. MATERIAL AND METHODS: The active compounds of each herb in ZJW were obtained from the HIT2.0 database with literature evidence. Single-cell RNA sequencing data of CRC were obtained from published studies (PMID: 32451460, 32103181, and 32561858). Pathway enrichment was analyzed using the reactome database, and intergenic correlation analysis was performed using the corrplot R software package. ZJW-regulated gene expression was verified by RT-qPCR. RESULTS: Huanglian and Wuzhu contain 19 and 4 compounds, respectively. Huang Lian targets 146 proteins, and Wu Zhu Yu targets 28 proteins based on evidence from the literature. ZJW regulates a range of biological processes associated with immune function, including cytokine signaling and Toll-Like Receptor 4 (TLR4) cascade. ZJW regulates malignant CRC cells, immune cells (including T-cells, B-cells, mast cells, NK/NKT cells, and myeloid cells), and other non-immune cells (including endothelial cells, enteric glial cells, and pericytes). We confirmed that ZJW significantly downregulated the expression of TIMP1 and MTDH. CONCLUSIONS: ZJW regulates a range of cells in the CRC microenvironment, including malignant CRC, immune cells, and stromal cells. In CRC cell lines, downregulation of TIMP1 and MTDH by ZJW may play an important role in the immunomodulation in CRC.

An investigation on the respiratory mechanics of mechanically ventilated patients during spontaneous breathing trials with enhanced low-level pressure support ventilation.

INTRODUCTION: Low-level pressure support ventilation (PSV) is most commonly adopted in spontaneous breathing trials (SBTs), and some have proposed setting the positive end-expiratory pressure (PEEP) to 0 cmH2 O in order to shorten the observation time of SBTs. This study aims to investigate the effects of two PSV protocols on the patients' respiratory mechanics. MATERIAL AND METHOD: A prospective randomized self-controlled crossover design was adopted in this study, which involved enrolling 30 difficult-to-wean patients who were admitted to the intensive care unit of the First Affiliated Hospital of Guangzhou Medical University between July 2019 and September 2021. Patients were subjected to the S group (pressure support: 8 cmH2 O, PEEP: 5 cmH2 O) and S1 group (PS: 8 cmH2 O, PEEP: 0 cmH2 O) for 30 min in a random order, and respiratory mechanics indices were dynamically monitored via a four-lumen multi-functional catheter with an integrated gastric tube. Among the 30 enrolled patients, 27 were successfully weaned. RESULT: The S group showed higher airway pressure (Paw), intragastric pressure (Pga) and airway pressure-time product (PTP) than the S1 group. The S group also showed a shorter inspiratory trigger delay, (93.80 ± 47.85) versus (137.33 ± 85.66) ms (P = 0.004); and fewer abnormal triggers, (0.97 ± 2.65) versus (2.67 ± 4.48) (P = 0.042) compared with the S1 group. Stratification based on the causes of mechanical ventilation revealed that under the S1 protocol, patients with chronic obstructive pulmonary disease (COPD) had a longer inspiratory trigger delay compared to both post-thoracic surgery (PTS) patients and patients with acute respiratory distress syndrome. Despite providing greater respiratory support, S group led to significant reductions in inspiratory trigger delay and less abnormal triggers compared to S1 group, especially among patients with chronic obstructive pulmonary disease. CONCLUSION: These findings suggest that the zero PEEP group was more likely to induce a higher number of patient-ventilator asynchronies in difficult-to-wean patients.

Short-term oral corticosteroids for initial treatment of moderate-to-severe persistent asthma: A double-blind, randomized, placebo-controlled trial.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate that on the basis of ICS-LABA treatment, whether or not adding on short course of oral corticosteroid could increase the rate of asthma control. METHODOLOGY: This was a double blind, randomized controlled study. Patients with moderate to severe persistent asthma who are maintenance treatment naïve were recruited from the out-patients clinic. All patients included in the study received ICS-LABA as initial treatment. Two weeks oral corticosteroid or placebo were added on at the beginning of treatment. All the subjects were followed-up by daily measurement of PEF and asthma diary for 12 week and spirometry at 4 weeks and 12 weeks. RESULTS: 13 cases were randomized to Corticosteroid group (M/F: 9/4, age: 45.0 ± 5.0 yrs), 11 to Placebo group (M/F: 4/7, age: 35.7 ± 9.6yrs). After treatment, significant improvement in ACT、ACQ、AQLQ、FEV1、FEV1% were observed in both groups as compared with baseline data (all P < 0.05). However, there were no significant difference between two groups in the improvement of ACT、ACQ、AQLQ、FEV1、FEV1% (all P > 0.05). After 4 weeks of treatment, total control was achieved in 3 (30.8%) in corticosteroid group and 2 (18.2%) in placebo group; Partial control was achieved in 7 (61.5%)in corticosteroid group and in 7 (63.6%) in placebo group. There was no significant difference in control rates between two groups (X2 = 0.919, P = 0.632). Similar findings were observed after 12 weeks of treatment. CONCLUSION: In maintenance treatment naïve moderate to severe persistent asthma, ICS-LABA therapy was adequate initial treatment for achieving asthma control in majority of the patients. Add on short course of oral corticosteroid provided no significant clinical benefit.

Evaluation of carbon dioxide rebreathing during exercise assisted by noninvasive ventilation with plateau exhalation valve.

Noninvasive ventilation with a plateau exhalation valve (PEV) is often used as an adjunct to exercise to achieve a physiologic training effect in severe chronic obstructive pulmonary disease (COPD) patients. However, during exercise, with the increase of exhalation flow and respiratory rate and limited capability of PEV to exhale gases out of the circuit, it is still unknown whether CO2 rebreathing occurs in COPD patients ventilated during exercise assisted by single-limb circuit with a PEV. A maximal symptom-limited cycle exercise test was performed while ventilated on pressure support (inspiratory:expiratory pressure 14:4 cmH2O) in 18 male patients with stable severe COPD (mean ± standard deviation, forced expiratory volume in 1 s: 29.5%±6.9% predicted). At rest and during exercise, breathing pattern, mean expiratory flow, mean expiratory flow of PEV, and the mean inspiratory fraction of CO2 (tidal fractional concentration of inspired CO2 [FiCO2]) reinsufflated from the circuit was measured for each breath. In comparison with rest, with the significant increase of mean expiratory flow (0.39±0.15 vs 0.82±0.27 L/s), fractional concentration of end-tidal CO2 (2.6%±0.7% vs 5.5%±0.6%), and the significant decrease of mean expiratory flow of PEV (0.41±0.02 vs 0.39±0.03 L/s), tidal FiCO2 significantly increased at peak exercise (0.48%±0.19% vs 1.8%±0.6%) in patients with stable severe COPD. The inflection point of obvious CO2 rebreathing was 0.67±0.09 L/s (95% confidence interval 0.60-0.73 L/s). Ventilated by a single-limb tubing with PEV caused CO2 rebreathing to COPD patients during exercise. Patients with mean expiratory flow >0.60-0.73 L/s may be predisposed to a higher risk of CO2 rebreathing.

Functional residual capacity in beagle dogs with and without acute respiratory distress syndrome.

BACKGROUND: Traditionally, the choice of tidal volume for mechanical ventilation was based on body weight (BW) and usually, predicted BW was used to correct actual BW inter-individual variations in obesity and muscle weight. The method of selecting tidal volume depended on the fact that normal lung volumes, especially functional residual capacity (FRC), were mainly determined by height (indirectly by predicted BW), sex and age in healthy persons. However, FRCs in patients with acute respiratory distress syndrome (ARDS) might not abide by the same rule and be significantly different from each other in patients with the same height and sex. We hypothesized that FRC was determined by body length (surrogate for predicted BW) and age in healthy male beagle dogs but not in lung injured ones. METHODS: A total of 24 dogs were recruited and ARDS model was induced by intravenous injection of oleic acid. FRC was measured by chest computer tomography. Blood gas analysis, extra vascular lung water and respiratory system mechanics were tested at baseline and post-lung injury. Age, body length and actual BW were also recorded before experiments. RESULTS: After lung injury, FRC decreased sharply from baseline (414±84) to (214±70) mL. For healthy lungs, FRC could be estimated by the following formula: FRC =21.86 × age (months) + 20.55 × body length (cm) - 1,337.98 (P<0.05), while for injured lungs, the formula of multiple linear regression was invalid (P=0.305). CONCLUSIONS: FRC was linearly related to body length in healthy dogs but not in lung injured ones. The traditional view of setting tidal volume based on predicted BW should be challenged cautiously.

Use of twitch mouth pressure to assess diaphragm strength in patients with chronic obstructive pulmonary disease.

This study was undertaken to determine whether twitch mouth pressure (TwPmo) can reliably assess diaphragm strength in patients with chronic obstructive pulmonary disease (COPD) using fully automatic trigger techniques. Fifteen patients with COPD were recruited. TwPmo, twitch oesophageal pressure (TwPes) and twitch transdiaphragmtic pressure (TwPdi) were generated by phrenic nerve stimulation and were measured using an inspiratory flow trigger (40 ml/s, Experiment 1) using an inspiratory pressure trigger (-5 cmH2O, Experiment 2) and using no trigger at functional residual capacity (Experiment 3). The correlation between TwPmo and TwPes was as follows: r=0.832; P<0.0001 (Experiment 1), r=0.900; P<0.0001 (Experiment 2); there was no significant correlation in Experiment 3. A Bland-Altman plot of the difference between TwPmo and TwPes showed the limits of agreement in Experiment (1) bias (range) 0.18 cmH2O (-2.05 to 2.41) and Experiment (2) bias (range) 0.32 cmH2O (-1.69 to 2.32). Measuring TwPmo using a fully automatic technique is a simple and convenient method for assessing diaphragm strength.