Esketamine Combined with Dexmedetomidine to reduce Visceral Pain During elective Cesarean Section Under Combined Spinal-Epidural Anesthesia: A double-Blind Randomized Controlled Study.

Purpose: We aimed to evaluate the effect of intravenous esketamine combined with dexmedetomidine as supplemental analgesia in reducing intraoperative visceral pain during elective cesarean section under combined spinal-epidural anesthesia (CSEA). Patients and Methods: A total of 269 parturients scheduled for elective cesarean section under CSEA between May 2023 and August 2023 were assessed. The parturients were randomly allocated to receiving either intravenous infusion of 0.3-mg/kg esketamine combined with 0.5-µg/kg dexmedetomidine (group ED, n=76), 0.5-µg/kg dexmedetomidine (group D, n=76), or normal saline (group C, n=76) after umbilical cord clamping. The primary outcome was intraoperative visceral pain. Secondary outcomes included the visual analog scale (VAS) score for pain evaluation and other intraoperative complications. Results: The incidence of visceral pain was lower in group ED [9 (12.7%)] than in group D [32 (43.8%)] and group C [36 (48.6%), P <0.0001]. The VAS score was also lower in group ED when exploring abdominal cavity [0 (0), P <0.0001] and suturing the muscle layer [0 (0), P =0.036]. The mean arterial pressure was higher in group D [83 (9) mmHg] and group ED [81 (11) mmHg] than in group C [75 (10) mmHg, P <0.0001] after solution infusion. The heart rate after infusion of the solution was lower in group D [80 (12) bpm] than in group C [86 (14) bpm] and group ED [85 (12) bpm, P = 0.016]. The incidence of transient neurologic or mental symptoms was higher in group ED compared to group C and group D (76.1% vs 18.9% vs 23.3%, P<0.0001). Conclusion: During cesarean section, 0.3-mg/kg esketamine combined with 0.5-µg/kg dexmedetomidine can alleviate visceral traction pain and provide stable hemodynamics. Parturients receiving this regimen may experience transient neurologic or mental symptoms that can spontaneously resolve at the end of the surgery.

Some parturients endure experience indescribable pain and discomfort during fetal delivery. Esketamine combined with dexmedetomidine can alleviate this pain during cesarean section under combined spinal-epidural anesthesia. However, after intravenous injection of esketamine and dexmedetomidine, the parturients may experience nightmares, dizziness, hallucinations, and drowsiness, etc.

Association between preoperative systemic immune inflammation index and postoperative sepsis in patients with intestinal obstruction: A retrospective observational cohort study.

BACKGROUND: Sepsis is a severe complication that results in increased morbidity and mortality after intestinal obstruction surgery. This study examined the role of preoperative systemic immune inflammation index (SII) for postoperative sepsis in intestinal obstruction patients. METHODS: Data on patients who underwent intestinal obstruction surgery were collected. SII was determined and separated into two groups (≤1792.19 and >1792.19) according to the optimal cut-off value of SII for postoperative sepsis. The odds ratio (OR) is calculated for the correlation between SII and postoperative sepsis. Additional analyses were used to estimate the robustness of SII. RESULTS: A total of 371 intestinal obstruction patients undergoing surgery were included in the final cohort, and 60 (16.17%) patients developed postoperative sepsis. Patients with an SII ＞1792.19 had a significantly higher risk for developing postoperative sepsis after multivariable adjustment [adjusted odds ratio = 2.12, 95% confidence interval: [1.02-4.40]]. The analysis of interaction showed no correlation between the preoperative SII and postoperative sepsis regarding age, hypertension, American Society of Anesthesiologists classification, blood loss, albumin, hemoglobin, creatinine, and leukocyte (all interactions p > .05). In subgroup analysis, all statistically significant subgroups showed that SII was a risk factor for postoperative sepsis (all p < .05). The analyses of subgroups and interactions revealed that the interaction effect of a preoperative SII ＞1792.19 and postoperative sepsis remained significant. A sensitivity analysis confirmed the robustness of the results. CONCLUSIONS: A preoperative SII ＞ 1792.19 was a risk factor for postoperative sepsis in patients undergoing intestinal obstruction surgery.

Transbrachial Artery as Single or Combined Approach for Complex Interventions in Patients with Peripheral Artery Disease.

BACKGROUND: This study aimed to assess the safety and efficacy of the transbrachial approach as a single or combined procedure for complex interventions in peripheral artery disease (PAD). METHODS: Between March 2011 and April 2021, 169 patients with PAD underwent endovascular therapy via the transbrachial approach as a single or dual procedure. Univariate and multivariate analyses were performed to evaluate the predictors of adverse events at the brachial puncture site. All demographic, clinical, and perioperative data were acquired from electronic medical records and retrospectively analyzed. RESULTS: Brachial artery access was used alone and in combination in 87 and 82 patients, respectively. Patients in the combined-approach group underwent more intraoperative stent implantations and had more vascular closure devices (VCD). Multivariate logistic regression analysis revealed that hypertension was an independent factor for higher rates of brachial puncture site adverse events (odds ratio, 4.76; 95% confidence interval, 1.33-16.97; P = 0.016). Brachial artery access-site complications occurred in 26 patients, including 6 (23.1%) major and 20 (76.9%) minor entry-site complications. Entry-site complications were observed in 21 (16.8%) and 5 (11.4%) patients assigned to manual compression and VCD groups, respectively. There were no significant intergroup differences in the incidence of major or minor complications. Interestingly, patients assigned to the VCD group did not experience major entry-site complications. CONCLUSIONS: The transbrachial approach, as a single or combined procedure, is a safe alternative to complex interventions in patients with PAD. Complications of brachial access progressively decrease with improved blood pressure control.

Efficiency and safety of dual pathway inhibition for the prevention of femoropopliteal artery restenosis in repeated endovascular interventions.

OBJECTIVE: There is a lack of consensus regarding the optimal strategy for evaluating the efficiency and safety of dual-pathway inhibition (DPI) in preventing femoropopliteal restenosis in patients undergoing repeated endovascular interventions. Despite several therapeutic interventions available for preventing femoropopliteal restenosis post repeated endovascular interventions, the ideal strategy, particularly evaluating the efficacy and safety of DPI, remains a matter of debate. METHODS: From January 2015 to September 2021, patients who underwent repeated endovascular interventions for femoropopliteal restenosis were compared with those who underwent DPI or dual antiplatelet therapy (DAPT) after surgery using a propensity score-matched analysis. The primary outcome was clinically driven target lesion revascularization (CD-TLR). The principal safety outcome was a composite of major bleeding and clinically relevant non-major (CRNM) bleeding. To further enhance the rigor, Kaplan-Meier plots, Cox proportional hazards modeling, and sensitivity analyses, as well as subgroup analyses were employed, reducing potential confounders. RESULTS: A total of 441 patients were included in our study, of whom 294 (66.7%) received DAPT and 147 (33.1%) received DPI, with 114 matched pairs (mean age, 72.21 years; 84.2% male). Cumulative probability of CD-TLR at 36 months in the DPI group (17%) trended lower than that in the DAPT group (32%) (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.26-0.78; P =.004). The cumulative probability of freedom from CD-TLR at 36 months in the DPI group was 83%. No significant difference was observed in the composite outcome of major or CRNM bleeding between the DPI and DAPT groups (HR, 1.26; 95% CI, 0.34 to 4.69; P = .730). The DPI group was associated with significantly lower rates of CD-TLR in the main subgroup analyses of diabetes (P = .001), previous smoking history (P = .008), longer lesion length (>10 cm) (P = .003), and treatment with debulking strategy (P = .003). CONCLUSIONS: In our investigation focused on CD-TLR, we found that DPI exhibited a significant reduction in the risk of reintervention compared with other treatment modalities. This underscores the potential of DPI as a viable therapeutic strategy in preventing reinterventions. Moreover, our assessment of safety outcomes revealed that the bleeding risks associated with DPI were on par with DAPT, thereby not compromising patient safety. These findings pave the way for potential broader clinical implications, emphasizing the effectiveness and safety of DPI in the context of reducing reintervention risks.

Hsa_circ_0010729 is Involved in Oxygen-Glucose Deprivation/Reoxygenation-Induced Human Microvascular Endothelial Cell Deprivation by Targeting miR-665/ING5.

Ischemic stroke is a disease with high mortality. Circular RNA_0010729 (hsa_circ_0010729) has been reported to be involved in ischemic heart disease. However, it is not clear whether hsa_circ_0010729 is involved in the regulation of ischemic stroke. In this study, we used oxygen-glucose deprivation/reoxygenation (OGD/R) to stimulate human brain microvascular endothelial cells (HBMECs) model to investigate the potential role of hsa_circ_0010729 in stroke in vitro. The expression levels of hsa_circ_0010729, miR-665, and ING5 in ischemic stroke were detected by quantitative real-time polymerase chain reaction (qRT-PCR). HBMECs proliferation was detected by CCK-8. Cell apoptosis was detected by flow cytometry. The levels of inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the related protein expression. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) were used to examine the target relationship between miR-665 and hsa_circ_0010729 or ING5. Compared with the control group, hsa_circ_0010729 and ING5 were highly expressed in OGD/R-induced HBMECs, while miR-665 was lowly expressed. Hsa_circ_0010729 silencing promoted OGD/R-induced cell proliferation and inhibited apoptosis. However, the effect of hsa_circ_0010729 down-regulation on OGD/R-induced cell was partially restored after co-transfection with miR-665 inhibitor. Overexpression of miR-665 can promote the proliferation and inhibit apoptosis of OGD/R-induced HBMECs by inhibiting ING5 expression. In OGD/R-induced HBMECs, hsa_circ_0010729 silencing decreased ING5 expression by upregulating miR-665. Hsa_circ_0010729 regulated miR-665/ING5 axis in OGD/R-induced HBMECs. Therefore, hsa_circ_0010729 may be a new therapeutic target for ischemic stroke.

Testis-specific protein, Y-linked 1 activates PI3K/AKT and RAS signaling pathways through suppressing IGFBP3 expression during tumor progression.

The testis-specific protein, Y-linked 1 (TSPY1), a newly recognized cancer/testis antigen, has been suggested to accelerate tumor progression. However, the mechanisms underlying TSPY1 cancer-related function remain limited. By mining the RNA sequencing data of lung and liver tumors from The Cancer Genome Atlas, we found frequent ectopic expression of TSPY1 in lung adenocarcinoma (LUAD) and liver hepatocellular carcinoma (LIHC), and the male-specific protein was associated with higher mortality rate and worse overall survival in patients with LUAD and LIHC. Overexpression of TSPY1 promotes cell proliferation, invasiveness, and cycle transition and inhibits apoptosis, whereas TSPY1 knockdown has the opposite effects on these cancer cell phenotypes. Transcriptomic analysis revealed the involvement of TSPY1 in PI3K/AKT and RAS signaling pathways in both LUAD and LIHC cells, which was further confirmed by the increase in the levels of phosphorylated proteins in the PI3K-AKT and RAS signaling pathways in TSPY1-overexpressing cancer cells, and by the suppression on the activity of these two pathways in TSPY1-knockdown cells. Further investigation identified that TSPY1 could directly bind to the promoter of insulin growth factor binding protein 3 (IGFBP3) to inhibit IGFBP3 expression and that downregulation of IGFBP3 increased the activity of PI3K/AKT/mTOR/BCL2 and RAS/RAF/MEK/ERK/JUN signaling in LUAD and LIHC cells. Taken together, the observations reveal a novel mechanism by which TSPY1 could contribute to the progression of LUAD and LIHC. Our finding is of importance for evaluating the potential of TSPY1 in immunotherapy of male tumor patients with TSPY1 expression.

TSPY1 suppresses USP7-mediated p53 function and promotes spermatogonial proliferation.

Testis-specific protein Y-linked 1 (TSPY1) is expressed predominantly in adult human spermatogonia and functions in the process of spermatogenesis; however, our understanding of the underlying mechanism is limited. Here we observed that TSPY1, as an interacting partner of TSPY-like 5 (TSPYL5), enhanced the competitive binding of TSPYL5 to ubiquitin-specific peptidase 7 (USP7) in conjunction with p53. This activity, together with its promotion of TSPYL5 expression by acting as a transcription factor, resulted in increased p53 ubiquitylation. Moreover, TSPY1 could decrease the p53 level by inducing the degradation of ubiquitinated USP7. We demonstrated that the promotion of p53 degradation by TSPY1 influenced the activity of p53 target molecules (CDK1, p21, and BAX) to expedite the G2/M phase transition and decrease cell apoptosis, accelerating cell proliferation. Taken together, the observations reveal the significance of TSPY1 as a suppressor of USP7-mediated p53 function in inhibiting p53-dependent cell proliferation arrest. By simulating TSPY1 function in Tspy1-deficient spermatogonia derived from mouse testes, we found that TSPY1 could promote spermatogonial proliferation by decreasing the Usp7-modulated p53 level. The findings suggest an additional mechanism underlying the regulation of spermatogonial p53 function, indicating the significance of TSPY1 in germline homeostasis maintenance and the potential of TSPY1 in regulating human spermatogonial proliferation via the USP7-mediated p53 signaling pathway.

Resolvin D1 Attenuates Mpp+-Induced Parkinson Disease via Inhibiting Inflammation in PC12 Cells.

BACKGROUND We investigated the influence of Resolvin D1 (RvD1) on the inflammatory response in PC12 cells (a cell model of Parkinson disease, PD). MATERIAL AND METHODS 4 mmol/L 1-methyl-4-phenylpyridinium ion (Mpp+) was used in PC12 cells for an in vitro PD model. 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to explore PC12 cell viability. Western blot (WB) experiments were used to identify nuclear factor-κB (NF-κB), phosphorylated extracellular signal-regulated kinase (p-ERK)/p-Jun N-terminal kinase (JNK)/p-P38 mitogen-activated protein kinase (MAPK), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 protein levels. Transcription levels of inflammatory factors, for instance, TNF-α and IL-6, were explored by real-time quantitative polymerase chain reaction (RT-QPCR). Lactic dehydrogenase (LDH) level was detected by enzyme-linked immunosorbent (ELISA). Cell apoptosis was assessed by Annexin-V Fluorescein (FITC) kit. RESULTS RvD1 dose-dependently inhibited MPP+ induced upregulation of PC12 cell apoptosis/cellular damage/TNF-α and p-P38/p-ERK/NF-κB as well as downregulation of PC12 cell viability. CONCLUSIONS We can draw the conclusion that RvD1 attenuates PD via inhibiting Mpp+-induced inflammation in PC12 cells.

Evidence for the involvement of the proximal copy of the MAGEA9 gene in Xq28-linked CNV67 specific to spermatogenic failure.

Spermatogenic failure characterized by impaired sperm production is a common multifactorial disease with molecular and cytogenetic causes for its extreme phenotype that include azoospermia and severe oliogzoospermia. Recently, a high-resolution array-comparative genomic hybridization analysis of the X chromosome and a subsequent cohort study revealed three X-linked microdeletions (CNV64, CNV67, and CNV69) that were associated with decreased sperm production in a mixed group that included Spanish and Italian males. To confirm their spermatogenic effect, we examined the hemizygous deletions and copy dosage of the MAGE family member A9 (MAGEA9) gene, which is a potential X-linked candidate for the CNV67-related spermatogenic phenotype, to investigate their association with spermatogenic failure in 1722 Han males from southwest China. The individuals in this group consisted of 884 patients with idiopathic azoospermia/oliogzoospermia and 838 controls with normozoospermia. Our results showed that both CNV64 and CNV69 were more common in patients than in controls. Similar to that reported previously, the CNV67 was also identified as being specific to spermatogenic failure in our population, although it was rare. More importantly, the paralog ratio tests and sequence family variant analyses provided evidence that the CNV67 might cause a partial deletion of the proximal copy of the MAGEA9 and suggests that CNV67-related spermatogenic failure may be attributed to the functional defect of the Cancer/Testis gene. Our findings highlight the potential of the Xq-linked CNV67 to serve as a novel detection target in the etiological diagnosis of spermatogenic failure and male infertility, although its pathogenic mechanism remains to be elucidated.