Single-cell transcriptomics reveals writers of RNA modification-mediated immune microenvironment and cardiac resident Macro-MYL2 macrophages in heart failure.

BACKGROUND: Heart failure (HF), which is caused by cardiac overload and injury, is linked to significant mortality. Writers of RNA modification (WRMs) play a crucial role in the regulation of epigenetic processes involved in immune response and cardiovascular disease. However, the potential roles of these writers in the immunological milieu of HF remain unknown. METHODS: We comprehensively characterized the expressions of 28 WRMs using datasets GSE145154 and GSE141910 to map the cardiac immunological microenvironment in HF patients. Based on the expression of WRMs, the immunological cells in the datasets were scored. RESULTS: Single-cell transcriptomics analysis (GSE145154) revealed immunological dysregulation in HF as well as differential expression of WRMs in immunological cells from HF and non-HF (NHF) samples. WRM-scored immunological cells were positively correlated with the immunological response, and the high WRM score group exhibited elevated immunological cell infiltration. WRMs are involved in the differentiation of T cells and myeloid cells. WRM scores of T cell and myeloid cell subtypes were significantly reduced in the HF group compared to the NHF group. We identified a myogenesis-related resident macrophage population in the heart, Macro-MYL2, that was characterized by an increased expression of cardiomyocyte structural genes (MYL2, TNNI3, TNNC1, TCAP, and TNNT2) and was regulated by TRMT10C. Based on the WRM expression pattern, the transcriptomics data (GSE141910) identified two distinct clusters of HF samples, each with distinct functional enrichments and immunological characteristics. CONCLUSION: Our study demonstrated a significant relationship between the WRMs and immunological microenvironment in HF, as well as a novel resident macrophage population, Macro-MYL2, characterized by myogenesis. These results provide a novel perspective on the underlying mechanisms and therapeutic targets for HF. Further experiments are required to validate the regulation of WRMs and Macro-MYL2 macrophage subtype in the cardiac immunological milieu.

The risk of all-cause death with dapagliflozin versus placebo: a systematic review and meta-analysis of phase III randomized controlled trials.

BACKGROUND: Dapagliflozin has proven cardioprotective and nephroprotective effects. However, the risk of all-cause death with dapagliflozin remains unclear. RESEARCH DESIGN AND METHODS: We performed a meta-analysis of phase III randomized controlled trials (RCTs) for the risk of all-cause death and safety events with dapagliflozin compared to placebo. PubMed and EMBASE were searched from inception to 20 September 2022. RESULTS: Five trials were included in the final analysis. Compared with the placebo, dapagliflozin demonstrated an 11.2% reduction in the risk of all-cause death (OR 0.88, 95% CI 0.81-0.94). No statistically significant difference in urinary tract infection (OR: 0.95, 95% CI: 0.78 to 1.17), bone fracture (OR: 1.06, 95% CI: 0.94 to 1.20), and amputation (OR: 1.01, 95% CI: 0.82 to 1.23) was observed between patients treated with dapagliflozin and placebo. Compared with placebo, dapagliflozin was associated with a significant reduction in acute kidney injury (OR: 0.71, 95% CI: 0.60 to 0.83), and increased the risk of genital infection (OR: 8.21, 95% CI: 4.19 to 16.12). CONCLUSIONS: Dapagliflozin was associated with significantly reduced all-cause death and increased genital infection. Dapagliflozin was safe concerning urinary tract infection, bone fracture, amputation, and acute kidney injury, compared with the placebo.

Indirect comparison of SGLT2 inhibitors in patients with established heart failure: evidence based on Bayesian methods.

AIMS: Head-to-head comparisons among SGLT2 inhibitors treatments in established heart failure remain absent. We conducted a systematic review of dedicated heart failure trials to assess indirectly the composite outcomes and individual clinical endpoints among SGLT2 inhibitor treatments. METHODS AND RESULTS: We systematically reviewed randomized controlled trials comparing SGLT2 inhibitors versus placebo in patients with established heart failure. A Bayesian approach to network meta-analysis was applied. Five trials including four treatment strategies were included in this study. The composite of cardiovascular death or hospitalization for heart failure showed no significant difference in the comparison between dapagliflozin and empagliflozin (OR 1.00, 95% CI 0.66-1.55), dapagliflozin and sotagliflozin (OR 1.54, 95% CI 0.91-2.65), and empagliflozin and sotagliflozin (OR 1.53, 95% CI 0.90-2.69). All-cause mortality showed no significant difference in the comparison between dapagliflozin and empagliflozin (OR 0.92, 95% CI 0.711-1.18), dapagliflozin and sotagliflozin (OR 1.05, 95% CI 0.68-1.59), and empagliflozin and sotagliflozin (OR 1.14, 95% CI 0.74-1.73). Cardiovascular death showed no significant difference in the comparison between dapagliflozin and empagliflozin (OR 0.94, 95% CI 0.71-1.23), dapagliflozin and sotagliflozin (OR 0.96, 95% CI 0.61-1.55), and empagliflozin and sotagliflozin (OR 1.03, 95% CI 0.64-1.66). Hospitalization for heart failure showed no significant difference in the comparison between dapagliflozin and empagliflozin (OR 1.13, 95% CI 0.64-1.97), dapagliflozin and sotagliflozin (OR 1.56, 95% CI 0.74-3.15), and empagliflozin and sotagliflozin (OR 1.39, 95% CI 0.68-2.78). CONCLUSIONS: In patients with established heart failure, there was no significant difference of the major efficacy outcomes among SGLT2 inhibitor treatments; however, sotagliflozin may be associated with the lowest risk of the composite of cardiovascular death or hospitalization for heart failure, and dapagliflozin may be associated with the lowest risk of all-cause and cardiovascular mortality.

SGLT2 inhibitors for the composite of cardiorenal outcome in patients with chronic kidney disease: A systematic review and meta-analysis of randomized controlled trials.

To conduct a systematic review and meta-analysis of specific chronic kidney disease (CKD) trials focusing on the composite of cardiorenal outcome, and assess indirectly the clinical outcome of treatments with three inhibitors of sodium-glucose cotransporter-2 (SGLT2) by Bayesian network meta-analysis, we used PubMed and Embase for randomized controlled trials comparing the efficacy of SGLT2 inhibitors in patients with established CKD. We estimated the composite of cardiorenal outcome of SGLT2 inhibitors versus control by pairwise meta-analysis. We included three trials including four treatment strategies (canagliflozin, dapagliflozin, sotagliflozin, and placebo) that met our inclusion criteria. SGLT2 inhibitors reduced the composite of cardiorenal outcome by 27.5% (OR 0.70, 95% CI 0.57-0.86, I2 = 72%). Results were corroborated in subgroup analysis. SGLT2 inhibitors reduced the composite of cardiorenal outcome in patients with and without diabetes (OR 0.72, 95% CI 0.60-0.86, and OR 0.51, 95% CI 0.35-0.75, respectively). The composite of cardiorenal outcome showed no significant difference in the comparison among three drugs: canagliflozin and dapagliflozin (OR 1.14, 95% CI 0.46-3.16), canagliflozin and sotagliflozin (OR 0.79, 95% CI 0.30-2.06), dapagliflozin and sotagliflozin (OR 0.69, 95% CI 0.26-1.73). Dapagliflozin was identified as having the lowest risk of the composite of cardiorenal outcome. In conclusion, SGLT2 inhibitors have robust benefits on the composite of cardiorenal outcome in patients with CKD. There was no significant difference in the composite of cardiorenal outcome among treatments with three SGLT2 inhibitors; however, dapagliflozin may be associated with the lowest risk of the composite of cardiorenal outcome.

Application of Plastic Sheet Barrier and Video Intubating Stylet to Protect Tracheal Intubators During Coronavirus Disease 2019 Pandemic: A Taiwan Experience.

Since its outbreak in China, the Coronavirus disease 2019 (COVID-19) pandemic has caused worldwide disaster. Globally, there have been 71,581,532 confirmed cases of COVID-19, including 1,618,374 deaths, reported to World Health Organization (data retrieved on December 16, 2020). Currently, no treatment modalities for COVID-19 (e.g., vaccines or antiviral drugs) with confirmed efficacy and safety are available. Although the possibilities and relevant challenges of some alternatives (e.g., use of stem cells as immunomodulators) have been proposed, the personal protective equipment is still the only way to protect and lower infection rates of COVID-19 among healthcare workers and airway managers (intubators). In this article, we described the combined use of a plastic sheet as a barrier with the intubating stylet for tracheal intubation in patients needing mechanical ventilation. Although conventional or video-assisted laryngoscopy is more popular and familiar to other groups around the world, we believe that the video-assisted intubating stylet technique is much easier to learn and master. Advantages of the video stylet include the creation of greater working distance between intubator and patient, less airway stimulation, and less pharyngeal space needed for endotracheal tube advancement. All the above features make this technique reliable and superior to other devices, especially when a difficult airway is encountered in COVID scenario. Meanwhile, we proposed the use of a flexible and transparent plastic sheet to serve as a barrier against aerosol and droplet spread during airway management. We demonstrated that the use of a plastic sheet would not interfere or hinder the intubator's maneuvers during endotracheal intubation. Moreover, we demonstrated that the plastic sheet was effective in preventing the spread of mist and water spray in simulation models with a mannequin. In our experience, we found that this technique most effectively protected the intubator and other operating room personnel from infection during the COVID-19 pandemic.

[Effects of Modified Ruji Recipe in Preventing Relapse and Metastasis of Breast Cancer Patients with Negative Hormone Receptor].

Objective To observe the effect of Ruji Recipe (RR) (treated by syndrome typing) in preventing the relapse and metastasis of invasive ductal breast cancer patients with negative hormone receptor (HR) after surgery and chemotherapy. Methods Using a prospective, cohort method, 136 pa- tients with stage I - III C HR negative invasive ductal breast cancer were equally assigned to the treat- ment group (treated by RR in syndrome typing way) and the control group (routine follow-ups). Disease free survival (DFS) , overall survival (OS) , relapse and metastasis were observed in the two groups. Re- sults All patients were followed-up for 15 to 57 months, with the median follow-up of 44 months. The median DFS and OS had not reached. The 1. 0, 1. 5, 2. -0, and 3. 0 years DFS were 94.1 % (64/68) , 86. 4 % (51/59), 81. 8% (45/55), and 72. 0% (36/50) in the treatment group. They were 77. 9% (53/68), 67.2% (45)67), 60. 6% (40)66), and 54. 5% (36/66) in the control group. Significant difference existed in 1. 0, 1. 5, and 2. 0 years DFS between the two groups (X² = 7.403, 6.426, 6.459; P =0. 012, 0.013, 0. 016). No statistical difference existed in 1. 0, 1. 5, 2. 0, and 3. 0 years OS between the two groups (P >0. 05). Among triple negative breast cancer (TNBC) patients, 1. 0, 1. 5, 2. 0, and 3. 0 years DFS were 97. 0% (32/33), 92. 9% (26/28), 92.6% (2527), and 84. 6% (22/26) in the treatment group, 81. 5% (2227), 66. 7% (1827), 61. 5% (16/26), and 57. 7% (15/26) in the control group. Of them, significant difference existed in 1. 5, 2. 0, and 3. 0 years DFS between the two groups (X² =5. 893, 7. 293, 4. 591 ; P = 0. 015, 0. 007, 0. 032). At the end of follow-ups, relapse and metastasis occurred in 15 patients, local recur- rence in 2 patients, single organ metastasis in 6 patients, and multiple organs metastasis in 7 patients of the treatment group. The relapse and metastasis occurred in 30 patients , local recurrence in 2 patients , single organ metastasis in 12 patients, and multiple organs metastasis in 16 patients of the treatment group. Conclusions RR ( by syndrome typing) could improve DFS and delay progression of invasive ductal breast cancer patients with negative HR in the first 2 years after surgery. It also had certain value for relapse and metastasis of TNBC patients within 2 years.

[Effect of ruji recipe on the post-surgical survival of female breast cancer patients].

OBJECTIVE: To observe the effect of Ruji Recipe (RR) in preventing disease recurrence/metastasis and improving quality of life (QOL) for female breast cancer patients after operation. METHODS: Totally 102 female patients with stage I - III breast cancer were retrospectively analyzed. They were assigned to the treatment group (54 cases) and the control group (48 cases) according to whether they would rather accept RR therapy. Estrogen receptor/progesterone receptor (ER/PR) positive patients also accepted endocrine therapy. The overall survival (OS), disease-free survival (DFS), recurrence and metastasis, and QOL were compared between the two groups. RESULTS: Totally 100 patients completed the study. The median follow-up was 59 months. The median OS was 60 months in the treatment group and 52.5 months in the control group (chi2 = 3.274, P > 0.05). The median DFS was 55.0 months in the treatment group and 47.5 months in the control group (chi2 = 10.145, P < 0.01). The DFS rate was 75.9% (41/54) in the treatment group and 54.3% (25/46) in the control group (chi2 = -2.259, P < 0.05). There was statistical difference in the 2-, 3-, and 5-year DFS between the two groups (P < 0.01). There was statistical difference in the 2-year DFS 3-year DFS between stage II and III and stage III (P < 0.05, P < 0.01). There was statistical difference in the ER positive patients between 2-year DFS and 3-year DFS (P < 0.01, P < 0.05). There was statistical difference in the 3-and 5-year distant metastasis rate (DMR) in the treatment group, lower than that of the control group (3.7% vs 31.0%, 20.7% vs 60.7%; P < 0.01). By the end of follow-up, disease progression occurred in 13 cases of the treatment group, local recurrence in 3 cases, single organ metastasis in 7 cases, multi-metastasis in 3 cases, while the corresponding numbers were 21, 1, 11, and 9 in the control group (P < 0.05). As for 1 week before study and at 2-year follow-up using Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B) system, there was statistical difference in the QOL between the two groups (P < 0.05), and better effect was obtained in the treatment group. CONCLUSION: RR, as an assistant therapy, could improve the OS rate, the DFS rate, and the QOL for post-surgical female breast cancer patients in 2 -3 years.

Nitric oxide scavenger carboxy-PTIO reduces infarct volume following permanent focal ischemia.

BACKGROUND: Nitric oxide (NO) has been shown to play a dual role as a neuroprotectant and a neurotoxin in cerebral ischemia. Free radical scavengers protect brain tissue from ischemic injury. Consequently, we examined the neuroprotective action of NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), in cerebral ischemia induced by permanent middle cerebral artery occlusion (MCAO) in rats and mice. METHODS: All experiments were performed in a randomized fashion. In the first series of experiments, adult Sprague-Dawley rats (n = 31) subjected to permanent MCAO were treated with carboxy-PTIO (0.3, 0.6 mg/kg) or vehicle (normal saline) injected intraperitoneally (IP) 1 hr before permanent MCAO. In the second series of experiments, adult C57BL/6NCrj mice (n = 49) were treated with carboxy-PTIO (0.6, 1.2 mg/kg) or vehicle saline 30 min following MCAO. Neurobehavioral scores were determined 22-24 hr following permanent MCAO and infarct volumes determined by quantitative image analysis of 2, 3, 5-triphenyltetrazolium (TTC)-stained brain sections. RESULTS: Pre-treatment with carboxy-PTIO at 0.6 mg/kg IP in rats significantly attenuated infarct volume (19.9 +/- 2.9%; n = 10) as compared with vehicle-treated controls (29.2 +/- 2.7%; n = 16), but not at 0.3 mg/kg (28.3 +/- 8.4%; n = 5). Post-MCAO treatment in mice with 0.6 mg/kg carboxy-PTIO (30.3 +/- 3.9%; n = 16) significantly attenuated infarct volume as compared with vehicle-treated controls (46.1 +/- 2.8%; n = 18). CONCLUSIONS: These data demonstrate that NO scavenger, carboxy-PTIO, provides significant ischemic neuroprotection when given as a pre-treatment as well as after the onset of permanent focal ischemia in two animal species.

Comparison of the anesthesia profiles between sevoflurane-nitrous oxide and propofol-nitrous oxide conveyed by laryngeal mask airway in patients undergoing ambulatory gynecological surgery.

BACKGROUND: The major purpose of this study is to evaluate and compare the clinical characteristics of sevoflurane-nitrous oxide and propofol-nitrous oxide anesthesias conveyed by laryngeal mask airway (LMA) in patients for gynecological procedures. METHODS: Eighty female patients were randomly assigned to one of the two groups: Group I, inhalational induction at vital capacity with 8% sevoflurane and 67% nitrous oxide in oxygen; Group II, induction with intravenous propofol at 2 mg/kg followed by intravenous infusion at 6 mg/kg/hr. The LMA was inserted after loss of response to jaw thrusting. After successful insertion, in group I anesthesia was maintained with sevoflurane and 67% nitrous oxide in O2 and in group II anesthesia was maintained with propofol at 6 mg/kg/hr and nitrous oxide 67% in oxygen. Anesthetic profiles, including insertion event, postoperative nausea and vomiting, and hemodynamic alterations were compared. RESULTS: Demographic data were comparable in the two groups. After induction, in group II unconsciousness was produced 59 sec shorter than that in group I for placement of LMA. Group I had a higher statistically significant rate of cough upon induction, and by the same token postoperative nausea and vomiting. There were no significant differences in hemodynamic alterations, as well as time to open eyes on command, and time to regain orientation. CONCLUSIONS: Intravenous propofol in combination with 67% nitrous oxide in oxygen technique provided better clinical profiles, compared with sevoflurane-nitrous oxide technique through the use of LMA in gynecological patients undergoing ambulatory short procedures.