Association between driving pressure-guided ventilation and postoperative pulmonary complications in surgical patients: a meta-analysis with trial sequential analysis.

BACKGROUND: Prior studies have reported inconsistent results regarding the association between driving pressure-guided ventilation and postoperative pulmonary complications (PPCs). We aimed to investigate whether driving pressure-guided ventilation is associated with a lower risk of PPCs. METHODS: We systematically searched electronic databases for RCTs comparing driving pressure-guided ventilation with conventional protective ventilation in adult surgical patients. The primary outcome was a composite of PPCs. Secondary outcomes were pneumonia, atelectasis, and acute respiratory distress syndrome (ARDS). Meta-analysis and subgroup analysis were conducted to calculate risk ratios (RRs) with 95% confidence intervals (CI). Trial sequential analysis (TSA) was used to assess the conclusiveness of evidence. RESULTS: Thirteen RCTs with 3401 subjects were included. Driving pressure-guided ventilation was associated with a lower risk of PPCs (RR 0.70, 95% CI 0.56-0.87, P=0.001), as indicated by TSA. Subgroup analysis (P for interaction=0.04) found that the association was observed in non-cardiothoracic surgery (nine RCTs, 1038 subjects, RR 0.61, 95% CI 0.48-0.77, P< 0.0001), with TSA suggesting sufficient evidence and conclusive result; however, it did not reach significance in cardiothoracic surgery (four RCTs, 2363 subjects, RR 0.86, 95% CI 0.67-1.10, P=0.23), with TSA indicating insufficient evidence and inconclusive result. Similarly, a lower risk of pneumonia was found in non-cardiothoracic surgery but not in cardiothoracic surgery (P for interaction=0.046). No significant differences were found in atelectasis and ARDS between the two ventilation strategies. CONCLUSIONS: Driving pressure-guided ventilation was associated with a lower risk of postoperative pulmonary complications in non-cardiothoracic surgery but not in cardiothoracic surgery. SYSTEMATIC REVIEW PROTOCOL: INPLASY 202410068.

Cannabinoid receptor 2 alleviates sepsis-associated acute lung injury by modulating maturation of dendritic cells.

BACKGROUND: Dendritic cells (DCs) play a key role in a variety of inflammatory lung diseases, but their role in sepsis-associated acute lung injury (SA-ALI) is currently not been illuminated. Cannabinoid receptor 2 (CNR2) has been reported to regulate the DCs maturation. However, whether the CNR2 in DCs contributes to therapeutic therapy for SA-ALI remain unclear. In current study, the role of CNR2 on DCs maturation and inflammatory during SA-ALI is to explored. METHODS: First, the CNR2 level was analyzed in isolated Peripheral Blood Mononuclear Cells (PBMCs) and Bronchoalveolar Lavage Fluid (BALF) from patient with SA-ALI by qRT-PCR and flow cytometry. Subsequently, HU308, a specific agonist of CNR2, and SR144528, a specific antagonist of CNR2, were introduced to explore the function of CNR2 on DCs maturation and inflammatory during SA-ALI. Finally, CNR2 conditional knockout mice were generated to further confirm the function of DCs maturation and Inflammation during SA-ALI. RESULTS: First, we found that the expression of CNR2 on DCs was decreased in patient with SA-ALI. Besides, the result showed HU308 could decrease the maturation of DCs and the level of inflammatory cytokines, simultaneously reduce pulmonary pathological injury after LPS-induced sepsis in mice. In contrast of HU308, SR144528 exhibits opposite function of DCs maturate, inflammatory cytokines and lung pathological injury. Furthermore, comparing with SR144528 treatment, similar results were obtained in DCs specific CNR2 knockout mice after LPS treatment. CONCLUSION: CNR2 could alleviate SA-ALI by modulating maturation of DCs and inflammatory factors levels. Targeting CNR2 signaling specifically in DCs has therapeutic potential for the treatment of SA-ALI.

Exosomal miR-127-5p from BMSCs alleviated sepsis-related acute lung injury by inhibiting neutrophil extracellular trap formation.

Neutrophil extracellular traps (NETs) play an important role in sepsis-related acute lung injury (ALI). Bone marrow mesenchymal stem cells (BMSCs)-derived exosomes and miRNA are becoming promising agents for the treatment of ALI. The current study aimed to elucidate the mechanism by BMSCs-derived exosomes carrying miR-127-5p inhibiting to the formation of NETs in sepsis-related ALI. We successfully isolated exosomes from BMSCs and confirmed that miR-127-5p was enriched in the exosomes. ALI mice treated with BMSCs-derived exosomes histologically improved, and the release of NETs and inflammatory factors in lung tissue and peripheral blood of mice also decreased compared with LPS group, while the protective effect of exosomes was attenuated after the knockdown of miR-127-5p. Using dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay, we identified CD64 as a direct target of miR-127-5p. Meanwhile, BMSCs-derived exosomes can synergize with anti-CD64 mab in ALI mice to reduce tissue damage, inhibit the release of inflammatory factors and NETs formation. The synergistic effect of exosomes was attenuated when miR-127-5p was down-regulated. These findings suggest that exosomal miR-127-5p derived from BMSCs is a potential therapeutic agent for treatment of sepsis-induced ALI through reducing NETs formation by targeting CD64.

Pre-intensive care unit use of selective serotonin reuptake inhibitors and mortality in critically ill adults with mental disorders: analysis from the MIMIC-IV database.

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed drugs for mental disorders in critically ill patients. We performed a retrospective cohort study to investigate the association between pre-ICU use of SSRIs and mortality in critically ill adults with mental disorders. We identified critically ill adults with mental disorders based on the Medical Information Mart in Intensive Care-IV database. The exposure was the use of SSRIs during the period after hospital admission and before ICU admission. The outcome was in-hospital mortality. Time-dependent Cox proportional hazards regression models were used to estimate the adjusted hazard ratio (aHR) with 95% confidence interval (CI). To further test the robustness of the results, we performed propensity score matching and marginal structural Cox model estimated by inverse probability of treatment weighting. The original cohort identified 16601 patients. Of those, 2232 (13.4%) received pre-ICU SSRIs, and 14369 (86.6%) did not. Matched cohort obtained 4406 patients, with 2203 patients in each group (SSRIs users vs. non-users). In the original cohort, pre-ICU use of SSRIs was associated with a 24% increase in the hazard for in-hospital mortality (aHR, 1.24; 95% CI, 1.05-1.46; P = 0.010). The results were robust in the matched cohort (aHR, 1.26; 95% CI, 1.02-1.57; P = 0.032) and the weighted cohort (aHR, 1.43; 95% CI, 1.32-1.54; P < 0.001). Pre-ICU use of SSRIs is associated with an increase in the hazard for in-hospital mortality in critically ill adults with mental disorders.

[Mining and discovery for active components of "Coptidis Rhizome-Magnoliae Officinalis Cortex" based on network pharmacology].

To mine and discover the active components of " Coptidis Rhizome-Magnoliae Officinalis Cortex( C&M) " based on the network pharmacology,integrate and analyze the potential targets and mechanisms. The TCMSP database was used to screen active ingredients. TTD and Drug Bank databases were used to predict the potential targets by referring to relevant literature,and the pathway annotation technology was used to enrich and analyze the active ingredients and potential targets of " C&M". A total of 29 potential target active ingredients were screened from " C&M",including 12 alkaloids components such as( R)-canadine,berberine,coptisine,and palmatine; 3 lignans consisting of magnolol,honokiol and obovatol; 6 volatile oils consisting of α-eudesmol,ß-eudesmol,eucalyptol and so on,and flavonoids including quercetin and neohesperidin. Corresponding 199 predicted targets were screened out,mainly including PTGS2,PTGS1,NCOA2,Hsp90 AB1,and so on. 72 signaling pathways were involved,8 of which were related to cancer,such as prostate cancer,bladder cancer,and pancreatic cancer; 9 of which were related to endocrine,including oxytocin signaling pathway,insulin signaling pathway,thyroid hormone signaling pathway and so on,as well as inflammation-related pathway. This study has preliminarily mined and discovered the main active components and potential targets of " C&M",providing material source for the study on the preparation of structural components of traditional Chinese medicine.

[Expressions of cyclooxygenase-2 and basic fibroblast growth factor in nasopharyngeal carcinoma and their association with radiotherapy sensitivity].

OBJECTIVE: To detect the expressions of cyclooxygenase-2 (COX-2) and basic fibroblast growth factor (bFGF) and evaluate their value in predicting the radiotherapy sensitivity in nasopharyngeal carcinoma (NPC). METHODS: The expressions of COX-2 and bFGF were detected immunohistochemically in biopsy samples of NPC, and their relationship with the radiotherapy sensitivity of the tumors were analyzed. RESULTS: In 97 NPC cases, the positivity rates of COX-2 and bFGF were 71.1% (69/97) and 64.9% (63/97), respectively. Correlation analysis demonstrated that a positive COX-2 expression was positively correlated with an advanced T status and N status, and bFGF expression was positively associated with an advanced N status in NPCs. In radiotherapy-sensitive and radiotherapy-insensitive cases, the positive rate of COX-2 was 62.8% and 92.6%, and that of bFGF was 57.1% and 85.2%, respectively. The expression of COX-2 was positively correlated with that of bFGF (r=0.486, P<0.05). The radiotherapy sensitivity differed significantly among patients with different statuses of COX-2 and bFGF positivity. CONCLUSION: COX-2 and bFGF can be effective and sensitive biomarkers for predicting radiotherapy sensitivity in NPC.

[An experiment study of protection and treatment of Kudan granule on rats of pulmonary fibrosis induced by pinyangmycin].

OBJECTIVE: To explore the protection and treatment effects of Kudan granule on rats of pulmonary fibrosis induced by pinyangmycin. METHOD: In asepsis condition, rat was anaesthetized by 3.5% chloral hydrate, inserted the needle above the bifurcation of trachea and injecting 5 mg x kg(-1) pinyangmycin normal saline solution. RESULT: For model-group rats, after injecting pinyangmycin at 7, 14, 28, 56 days, there were mass inflammation cell infiltration at pulmonary alveoli and interstitial, the pulmonary alveolar wall and interstitial thickened obviously, and the pulmonary interval broadened distinctly. The structure of collagen fiber was destroyed, and the pulmonary alveoli disappeared. By Masson dyeing, there were hunk collagen fiber and the consolidation of lung had come into being. Compared with the model group, the rats of Kudan granule big-dose group, at 7, 14, 28, 56 days after injecting pinyangmycin, there were still much inflammation cell infiltration at pulmonary alveoli and interstitial, pulmonary interstitial edema and spotty necrosis, thickened alveolar wall, broadened pulmonary interval, and much collagen fiber in pulmonary interstitial, but there was not bunk the consolidation of lung. The curative effect of Kudan granule small-dose group was not better than that of Kudan granule big-dose group, because there were still bunk collagen fiber and the consolidation of lung in pulmonary interstitial. Although the destroyed area was more than 50%, it was better than that of the model-group. CONCLUSION: The big-dose Kudan granule show the better function of protection and treatment for pulmonary fibrosis of rats induced by pinyangmycin.

[Effect and mechanism of bishudiwan(BSDW) against allergy].

OBJECTIVE: To investigate the effect and mechanism of BSDW on the model of allergic rhinitis and the model of guinea pigs by histamine shocking in guinea pigs. METHOD: Using the model of allergic rhinitis in guinea pigs caused by 10% TDI, we observed the effect of BSDW on physiological and pathological symptoms of allergic rhinitis in guinea pigs, the effect of the levels of serum IgE and serum and nasal histamine. Using the model of guinea pigs by histamine shocking, we observed the effect of BSDW on physiological symptoms in guinea pigs. RESULT: BSDW significantly relieved the pathological symptoms of allergic rhinitis in guinea pigs, alleviated the hyperplasia of columnar epithelium, decreased the number of monocyte and eosinocyte compared with the model group. It also reduced the levels of serum IgE, and decreased the release of serum and nasal histamine. BSDW significantly prolonged the occurent time of gasping, eclampsia and death caused by shock, reduced the times of gasping in the model of guinea pigs by histamine shocking. CONCLUSION: BSDW has significant effect against allergy. The mechanism relates to its effects of decreasing the levels of serum IgE and inhibiting the release of serum and nasal histamine.

Effect of jianpiyiwei capsule on gastric precancerous lesions in rats.

AIM: To evaluate the therapeutic effect of compound Chinese drugs, Jianpiyiwei capsule (JPYW) on gastric precancerous lesions in rats and to explore its mechanism of action. METHODS: Model of gastric precancerous lesions was constructed in male Wistar rats: a metal spring was inserted and fixed through pyloric sphincter. One week after recovery, each rat was given 50-60 degrees hot paste containing 150 g/L NaCl 2 mL orally, twice a week for 15 weeks. Then 10 normal and 11 model rats were anaesthetized, after the measurement of gastric mucosa blood flow (GMBF), the rats were killed and the mucosal hexosamines and malonic dialdehyde (MDA) were measured. The morphological changes of gastric mucosa were observed macroscopically and microscopically, and by an automatic imaging analysis system. Other rats were treated with JPYW 1.5 g/kg.d(-1) or 4.5 g/kg.d(-1), or distilled water as negative control respectively (n=10 in each group). After 12 weeks, all the rats were examined as above. RESULTS: The gastric mucosa of model rats showed chronic atrophic gastritis with dysplasia and intestinal metaplasia (IM), GMBF and hexosamine content were reduced significantly and MDA was increased as compared to the normal group (P<0.01). After 12 weeks treatment, the pathological changes of the negative control group became worsened, while in JPYW treated groups the changes were modified with significant increase of GMBF and reduction of MDA, although the hexosamine concentration increased only mildly. CONCLUSION: JPYW increases GMBF and reduces MDA content in gastric mucosa and has therapeutic effects on gastric precancerous lesions.