Mitochondria protective and anti-apoptotic effects of peripheral benzodiazepine receptor and its ligands on the treatment of asthma in vitro and vivo.

BACKGROUND: Asthma is a prevalent respiratory inflammatory disease. Abnormal apoptosis of bronchial epithelial cells is one of the major factors in the progression of asthma. Peripheral benzodiazepine receptors are highly expressed in bronchial epithelial cells, which act as a component of the mitochondrial permeability transition pore to regulate its opening and closing and apoptosis of bronchial epithelial cells. We aimed to investigate the mechanisms by which peripheral benzodiazepine receptor and its ligands, agonist 4'-Chlorodiazepam (Ro5-4864) and antagonist 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide (PK 11,195), modulate the mitochondrial function and cell apoptosis in the treatment of asthma. METHODS: In vitro study, Ro5-4864 and PK 11,195 were utilized to pretreat cells prior to the inflammatory injury induced by Lipopolysaccharide. The reactive oxygen species, the apoptosis of cell, the mitochondrial membrane potentials, the ultrastructures of the mitochondria and the expression levels of peripheral benzodiazepine receptors and apoptosis-related proteins and genes were detected. In vivo study, mice were administrated intraperitoneally with Ro5-4864 and PK 11,195 before sensitized and challenged by ovalbumin. Serum IgE and bronchoalveolar lavage fluid cytokines were detected, and lung tissues were underwent the histopathological examination. RESULTS: The ligands of peripheral benzodiazepine receptor counteracted the effects of the increase of reactive oxygen species, the elevated extent of apoptosis, the decrease of mitochondrial membrane potentials and the disruption of mitochondrial ultrastructures induced by Lipopolysaccharide. The ligands also promoted the expression of anti-apoptosis-related proteins and genes and inhibited the expression of pro-apoptosis-related proteins and genes. Besides, the ligands reduced the levels of serum IgE and bronchoalveolar lavage fluid cytokines in asthmatic mice and attenuated the histopathological damage of lungs. CONCLUSION: Peripheral benzodiazepine receptor serves as a potential therapeutic target for the treatment of asthma, with its ligands exerting mitochondrial protective and anti-apoptotic effects on bronchial epithelial cells.

Efficacy and safety of chinese herbal foot bath for hypertension: A systematic review and meta-analysis.

BACKGROUND: Hypertension is a prevalent condition with significant impacts on human health. Chinese herbal foot bath, a traditional Chinese medicine treatment, is believed to help manage hypertension. OBJECTIVE: This systematic review aims to assess the efficacy of combining Chinese herbal foot bath with conventional treatment for hypertension. METHODS: A thorough search across eight databases was conducted to identify relevant studies on Chinese herbal foot bath for hypertension. Randomized controlled trials examining the benefits and risks of using Chinese herbal foot bath combined with conventional treatment for hypertension were included. Blood pressure changes before and after the Chinese herbal foot bath were assessed, and outcomes were analyzed using Review Manager 5.3 software. The certainty of evidence was evaluated using the GRADE tool. RESULTS: Compared to conventional treatment, Chinese herbal foot bath combined with conventional treatment demonstrated greater effectiveness in reducing systolic blood pressure (MD 6.69, 95% CI: 5.86 to 7.53, p < 0.00001) and diastolic blood pressure (MD 5.83, 95% CI: 5.23 to 6.43, p < 0.00001), which reported fewer adverse effects.These studies commonly present issues such as inadequate randomization, lack of blinding, and absence of independent testing for the purity or potency of herbs. CONCLUSION: The meta-analysis suggests that Chinese herbal foot bath combined with conventional treatment may effectively manage hypertension, with few adverse effects. However, high-quality clinical trials are still needed to confirm these findings due to methodological weaknesses in randomization, blinding, long-term follow-up, and independent testing for the purity and potency of herbs.

Comparison of the efficacy and comfort of high-flow nasal cannula with different initial flow settings in patients with acute hypoxemic respiratory failure: a systematic review and network meta-analysis.

BACKGROUND: High-flow nasal cannula (HFNC) has been proven effective in improving patients with acute hypoxemic respiratory failure (AHRF), but a discussion of its use for initial flow settings still need to be provided. We aimed to compare the effectiveness and comfort evaluation of HFNC with different initial flow settings in patients with AHRF. METHODS: Studies published by October 10, 2022, were searched exhaustively in PubMed, Embase, Web of Science, Cochrane Library (CENTRAL), and the China National Knowledge Infrastructure (CNKI) database. Network meta-analysis (NMA) was performed with STATA 17.0 and R software (version 4.2.1). A Bayesian framework was applied for this NMA. Comparisons of competing models based on the deviance information criterion (DIC) were used to select the best model for NMA. The primary outcome is the intubation at day 28. Secondary outcomes included short-term and long-term mortality, comfort score, length of ICU or hospital stay, and 24-h PaO2/FiO2. RESULTS: This NMA included 23 randomized controlled trials (RCTs) with 5774 patients. With NIV as the control, the HFNC_high group was significantly associated with lower intubation rates (odds ratio [OR] 0.72 95% credible interval [CrI] 0.56 to 0.93; moderate quality evidence) and short-term mortality (OR 0.81 95% CrI 0.69 to 0.96; moderate quality evidence). Using HFNC_Moderate (Mod) group (mean difference [MD] - 1.98 95% CrI -3.98 to 0.01; very low quality evidence) as a comparator, the HFNC_Low group had a slight advantage in comfort scores but no statistically significant difference. Of all possible interventions, the HFNC_High group had the highest probability of being the best in reducing intubation rates (73.04%), short-term (82.74%) and long-term mortality (67.08%). While surface under the cumulative ranking curve value (SUCRA) indicated that the HFNC_Low group had the highest probability of being the best in terms of comfort scores. CONCLUSIONS: The high initial flow settings (50-60 L/min) performed better in decreasing the occurrence of intubation and mortality, albeit with poor comfort scores. Treatment of HFNC for AHRF patients ought to be initiated from moderate flow rates (30-40 L/min), and individualized flow settings can make HFNC more sensible in clinical practice.

The effects of anesthesia methods and anesthetics on postoperative delirium in the elderly patients: A systematic review and network meta-analysis.

Study objective: Postoperative delirium (POD) is one of the serious postoperative complications in elderly patients, which is always related to long-term mortality. Anesthesia is often considered a risk factor for POD. This systematic review and network meta-analysis (NMA) aimed to assess the impact of different anesthesia methods and anesthetics on POD. Measurements: We searched for studies published in PubMed, Embase, Web of Science, Scopus, and Cochrane Library (CENTRAL) from inception to 18 March 2022. RevMan 5.3 and CINeMA 2.0.0 were used to assess the risk of bias and confidence. Data analysis using STATA 17.0 and R 4.1.2. STATA 17.0 was used to calculate the surface under the cumulative ranking curve (SUCRA) and provide network plots with CINeMA 2.0.0. NMA was performed with R 4.1.2 software gemtc packages in RStudio. Main results: This NMA included 19 RCTs with 5,406 patients. In the pairwise meta-analysis results, only regional anesthesia (RA) with general anesthesia (GA) vs. GA (Log OR: -1.08; 95% CI: -1.54, -0.63) were statistically different in POD incidence. In the NMA results, there was no statistical difference between anesthesia methods, and psoas compartment block (PCB) with bupivacaine was superior to the desflurane, propofol, sevoflurane, and spinal anesthesia with bupivacaine of POD occurrence. Conclusion: Our study indicated that RA and GA had no significant effect on POD, and there was no difference between anesthesia methods. Pairwise meta-analysis showed that, except for RA with GA vs. GA, the rest of the results were not statistically different. Besides, PCB with bupivacaine may benefit to reduce POD incidence. Systematic review registration: https://www.crd.york.ac.uk/prospero/dis play_record.php?ID=CRD42022319499, identifier PROSPERO 2022 CRD42022319499.

A necroptosis-related prognostic model for predicting prognosis, immune landscape, and drug sensitivity in hepatocellular carcinoma based on single-cell sequencing analysis and weighted co-expression network.

Background: Hepatocellular carcinoma (HCC) is a highly lethal cancer and is the second leading cause of cancer-related deaths worldwide. Unlike apoptosis, necroptosis (NCPS) triggers an immune response by releasing damage-related molecular factors. However, the clinical prognostic features of necroptosis-associated genes in HCC are still not fully explored. Methods: We analyzed the single-cell datasets GSE125449 and GSE151530 from the GEO database and performed weighted co-expression network analysis on the TCGA data to identify the necroptosis genes. A prognostic model was built using COX and Lasso regression. In addition, we performed an analysis of survival, immunity microenvironment, and mutation. Furthermore, the hub genes and pathways associated with HCC were localized within the single-cell atlas. Results: Patients with HCC in the TCGA and ICGC cohorts were classified using a necroptosis-related model with significant differences in survival times between high- and low-NCPS groups (p < 0.05). High-NCPS patients expressed more immune checkpoint-related genes, suggesting immunotherapy and some chemotherapies might prove beneficial to them. In addition, a single-cell sequencing approach was conducted to investigate the expression of hub genes and associated signaling pathways in different cell types. Conclusion: Through the analysis of single-cell and bulk multi-omics sequencing data, we constructed a prognostic model related to necroptosis and explored the relationship between high- and low-NCPS groups and immune cell infiltration in HCC. This provides a new reference for further understanding the role of necroptosis in HCC.

High-flow nasal cannula versus noninvasive ventilation in patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: During the novel coronavirus disease 2019 (COVID-19) pandemic raging around the world, the effectiveness of respiratory support treatment has dominated people's field of vision. This study aimed to compare the effectiveness and value of high-flow nasal cannula (HFNC) with noninvasive ventilation (NIV) for COVID-19 patients. METHODS: A comprehensive systematic review via PubMed, Web of Science, Cochrane, Scopus, WHO database, China Biology Medicine Disc (SINOMED), and China National Knowledge Infrastructure (CNKI) databases was conducted, followed by meta-analysis. RevMan 5.4 was used to analyze the results and risk of bias. The primary outcome is the number of deaths at day 28. The secondary outcomes are the occurrence of invasive mechanical ventilation (IMV), the number of deaths (no time-limited), length of intensive care unit (ICU) and hospital stay, ventilator-free days, and oxygenation index [partial pressure of arterial oxygen (PaO2)/fraction of inhaled oxygen (FiO2)] at 24 h. RESULTS: In total, nine studies [one randomized controlled trial (RCT), seven retrospective studies, and one prospective study] totaling 1582 patients were enrolled in the meta-analysis. The results showed that the incidence of IMV, number of deaths (no time-limited), and length of ICU stay were not statistically significant in the HFNC group compared with the NIV group (ps = 0.71, 0.31, and 0.33, respectively). Whereas the HFNC group performed significant advantages in terms of the number of deaths at day 28, length of hospital stay and oxygenation index (p < 0.05). Only in the ventilator-free days did NIV show advantages over the HFNC group (p < 0.0001). CONCLUSION: For COVID-19 patients, the use of HFNC therapy is associated with the reduction of the number of deaths at day 28 and length of hospital stay, and can significantly improve oxygenation index (PaO2/FiO2) at 24 h. However, there was no favorable between the HFNC and NIV groups in the occurrence of IMV. NIV group was superior only in terms of ventilator-free days.

Prophylactic hyperthermic intraperitoneal chemotherapy may benefit the long-term survival of patients after radical gastric cancer surgery.

Hyperthermic intraperitoneal chemotherapy (HIPEC) has been proven to improve the survival rate of gastric cancer and reduce peritoneal recurrence. We aimed to evaluate the effectiveness and safety of prophylactic HIPEC after radical gastric cancer surgery in this study. Researchers searched for studies published in PubMed, Embase, Web of science, Scopus, Cochrane, Clinical key databases and Microsoft Academic databases to identify studies that examine the impact of prophylactic HIPEC on the survival, recurrence and adverse events of patients undergoing radical gastric cancer surgery. RevMan 5.3 was used to analyze the results and risk of bias. The PROSERO registration number is CRD42021262016. This meta-analysis included 22 studies with a total of 2097 patients, 12 of which are RCTs. The results showed that the 1-, 3- and 5-year overall survival rate was significantly favorable to HIPEC (OR 5.10, 2.07, 1.96 respectively). Compared with the control group, the overall recurrence rate and peritoneal recurrence rate of the HIPEC group were significantly lower (OR 0.41, 0.24 respectively). Significantly favorable to the control group in terms of renal dysfunction and pulmonary dysfunction complications (OR 2.44, 6.03 respectively). Regarding the causes of death due to postoperative recurrence: liver recurrence, lymph node and local recurrence and peritoneal recurrence, the overall effect is not significantly different (OR 0.81, 1.19, 0.37 respectively). 1-, 3- and 5-year overall survival follow-up may be incremented by the prophylactic HIPEC, and which reduce the overall recurrence rate and peritoneal recurrence rate. HIPEC may have high-risk of pulmonary dysfunction and renal dysfunction complications. No difference has been found in the deaths due to recurrence after surgery.

Is gabapentin effective and safe in the treatment of chronic pelvic pain in women: a systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: Chronic pelvic pain (CPP) affects 2.1-24% of women, causing physical and psychological damage to women around the world. Based on the efficacy of gabapentin in the treatment of chronic pain, we conducted this study to evaluate the efficacy and safety of gabapentin in reducing pain in women with CPP. METHODS: Systematic searches were performed in the electronic databases of PubMed, Embase, Web of Science, Scopus, Cochrane, and Clinicalkey databases. Studies focused on comparing the efficacy of gabapentin and placebo in the treatment of female CPP patients were included. RevMan 5.4 was used to analyze the results and risk of bias. Two investigators independently selected eligible studies and extracted related pain scores and side effects for meta-analysis. RESULTS: In total, 4 RCTs were enrolled in the meta-analysis, totaling 425 patients. Among patients receiving gabapentin, the average pain scores in 3 and 6 months were significantly lower than those in the placebo group(p < 0.00001). The results showed that there was no statistical difference between gabapentin and placebo in the reduction of pain scores from baseline(p = 0.41). The incidence of side effects in the gabapentin group was significantly higher than that in the placebo group (p < 0.00001). CONCLUSION: This systematic review and meta-analysis demonstrated that for women with CPP, gabapentin was significantly different from placebo in average pain scores at 3 and 6 months. However, the two drugs did not differ in the reduction in pain scores from baseline. Gabapentin can bring more significant side effects, whether they are common side effects or serious side effects.

Anionic Redox Processes in Maricite- and Triphylite-NaFePO4 of Sodium-Ion Batteries.

In recent years, NaFePO4 has been regarded as one of the most promising cathode materials for next-generation rechargeable sodium-ion batteries. There is significant interest in the redox processes of rechargeable batteries for high capacity applications. In this paper, the redox processes of triphylite-NaFePO4 and maricite-NaFePO4 materials have been analyzed based on first-principles calculations and analysis of Bader charges. Different from LiFePO4, anionic (O2-) redox reactions are evidently visible in NaFePO4. Electronic structures and density of states are calculated to elaborate the charge transfer and redox reactions during the desodiation processes. Furthermore, we also calculate the formation energies of sodium extraction, convex hull, average voltage plateaus, and volume changes of Na1-x/12FePO4 with different sodium compositions. Deformation charge density plots and magnetization for NaFePO4 are also calculated to help understand the redox reaction processes.

Comparative study on the electronic structures and redox reactions in LiCrX2 and NaCrX2 (X = O and S).

LiCrO2 and NaCrO2 have been well-studied as cathode materials in lithium and sodium ion batteries, while the studies on LiCrS2 and NaCrS2 are relatively rare. In this work, a comparative study on the electronic structures and redox reactions in oxides (LiCrO2, NaCrO2) and sulfides (LiCrS2, NaCrS2) is performed. A first-principles method has been used to calculate the Bader charge transfer, the electronic structures and the magnetic moments during the entire delithiation or desodiation process. The Bader charge analysis suggests that all the S, O and Cr ions in LiCrX2 and NaCrX2 participate in the redox reactions, where the loss of electrons of S ions is clearly larger than that of O ions. Besides, the redox processes of Cr ions are of much less significance. It is noted that, in the sulfides, Cr ions even gain a small portion of electrons rather than losing electrons during the extraction of Li/Na ions. All the charge transfer happens between the S-3p/O-2p and the Cr-3d bands. The redox reactions of O or S ions originate from the energy levels of O/S being pushed towards/across the Fermi surface due to the strong p-d hybridization.