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Background Painless gastrointestinal endoscopy is widely used for the diagnosis and treatment of digestive diseases. At present, propofol is commonly used to perform painless gastrointestinal endoscopy, but the high dose of propofol often leads to a higher incidence of cardiovascular and respiratory complications. Studies have shown that the application of propofol combined with ketamine in painless gastrointestinal endoscopy is beneficial to reduce the dosage of propofol and the incidence of related complications. Esketamine is dextrorotatory structure of ketamine with a twice as great anesthetic effect as normal ketamine but fewer side effects. We hypothesized that esketamine may reduce the consumption of propofol and to investigate the safety of coadministration during gastrointestinal endoscopy. Methods A total of 260 patients undergoing painless gastrointestinal endoscopy (gastroscope and colonoscopy) were randomly divided into P group (propofol + saline), PK1 group (propofol + esketamine 0.05 mg/kg), PK2 group (propofol + esketamine 0.1 mg/kg), and PK3 group (propofol + esketamine 0.2 mg/kg). Anesthesia was achieved by 1.5 mg/kg propofol with different doses of esketamine. Propofol consumption per minute was recorded. Hemodynamic index, pulse oxygen saturation, operative time, induction time, awakening status, orientation recovery time, adverse events, and Mini-Mental State Examination (MMSE) were also recorded during gastrointestinal endoscopy. Results Propofol consumption per minute was 11.78, 10.56, 10.14, and 9.57 (mg/min) in groups P, PK1, PK2, and PK3, respectively; compared with group P, groups PK2 and PK3 showed a decrease of 13.92% ( P  = 0.021) and 18.76% ( P  = 0.000), respectively. In all four groups, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), but not pulse oxygen saturation (SpO 2 ) significantly decreased ( P  = 0.000) immediately after administration of induction, but there were no significant differences between the groups. The induction time of groups P, PK1, PK2, and PK3 was 68.52 ± 18.394, 64.83 ± 13.543, 62.23 ± 15.197, and 61.35 ± 14.470 s, respectively ( P  = 0.041). Adverse events and psychotomimetic effects were observed but without significant differences between the groups. Conclusions The combination of 0.2 mg/kg esketamine and propofol was effective and safe in painless gastrointestinal endoscopy as evidenced by less propofol consumption per minute, shorter induction time, and lower incidence of cough and body movement relative to propofol alone. The lack of significant differences in hemodynamic results, anesthesia-related indices, adverse events, and MMSE results showed the safety to apply this combination for painless gastrointestinal endoscopy. Trial registration This study was registered with China Clinical Trial Registration on 07/11/2020 (registration website: chictr.org.cn; registration numbers: ChiCTR https://clinicaltrials.gov/ct2/show/2000039750 ).

Brachial plexus root avulsion (BPRA) often occurs in high-speed traffic accidents or shoulder dystocia, resulting in motor dysfunction. S-ketamine, a clinical anesthetic and antidepressant drug, is an NMDA receptor antagonist that may be effective against glutamate excitotoxicity after nerve injury. Therefore, we aimed to elucidate the potential effectiveness of S-ketamine on motor function recovery after BPRA in mice. A mouse model of BPRA and reimplantation was established, and mice were randomly assigned to either the S-ketamine group or the control group, receiving a low, subanesthetic dose of S-ketamine or normal saline, respectively. The restoration of the motor neural circuit-from spinal cord and myocutaneous nerve to biceps muscle-was evaluated. Fluoro-Gold retrograde tracing was utilized to assess the connectivity between the central and peripheral nerve systems. Behavioral tests such as CatWalk, grooming test, and grip strength were applied to assess motor function recovery. The underlying mechanism was analyzed by Western blot, and the rescue experiment was assessed via motor function behavioral tests. S-ketamine increased motor neuron survival, enhanced central and peripheral nervous connectivity, promoted axon regeneration and remyelination, improved the neuromuscular junction integrity, and prevented muscle atrophy. As a result, motor function recovery was significantly improved, which was attributed to increased BDNF production via ERK-CREB phosphorylation. The BDNF receptor antagonist, ANA12, counteracted the functional recovery induced by S-ketamine. S-ketamine increases the BDNF concentration by ERK/CREB phosphorylation, thereby promoting motor neural circuit repair and facilitating motor function recovery.

Obesity has become a global health crisis. Laparoscopic bariatric surgery, a commonly used method for treating obesity, can significantly alter intracranial hemodynamics due to surgical positioning and pneumoperitoneum pressure, thereby increasing the likelihood of perioperative complications in obese individuals. Ciprofol, a novel propofol analog, offers advantages such as reduced side effects and enhanced stability, but its effects on brain blood flow regulation in obese patients are not yet fully understood. This clinical trial was designed to validate its superior efficacy in preserving cerebral perfusion and maintaining hemodynamic stability. The trial was structured as a randomized, double-blind research with parallel arms. Research was carried out from 1st February 2023 to 30th May 2023 in the First Affiliated Hospital of Jinan University. Patients, with body mass index ranging from 30.6 to 51.2 kg/m , scheduled for laparoscopic bariatric surgery, were randomly allocated to receive either propofol or ciprofol. For anesthesia induction and maintenance, participants in each group were administered propofol or ciprofol as the sedative agent. The mean cerebral blood flow velocities (CBFVm) were detected using transcranial doppler ultrasonography, and mean arterial pressure (MAP), heart rate and adverse events were recorded during surgery. A total of 43 patients were ultimately included in this study (21 in the propofol group and 22 in the ciprofol group). Compared with baseline, patients receiving propofol group exhibited marked reductions in CBFVm at T , T , T , T , T , T , T , T and MAP at T , T , T , T , T ( < 0.05), respectively. In contrast, ciprofol- administered participants demonstrated no significant change in CBFVm, and MAP only showed a significant decrease at T ( < 0.05). Although there was a certain difference in ΔCBFVm between the two groups, it was not statistically significant. Additionally, 13 patients (61.9%) in the propofol group experienced pain at the injection site, compared to only three patients (13.6%) in the ciprofol group ( = 0.001). Both groups experienced hypotension, respiratory depression, and bradycardia, but no significant differences were observed. This study found that, compared to propofol, ciprofol may be a better anesthetic choice for obese individuals receiving laparoscopic bariatric surgery, as it maintains CBFVm and hemodynamics more steadily, causes less injection discomfort, and demonstrates comparable safety and adverse event rates to those of propofol. [https://www.chictr.org.cn/showproj.html?proj=187919], identifier [ChiCTR2300067801].

Background It has been known that ABO blood groups are linked to the phenotypes of certain diseases; however, and the relationship between ABO blood groups and postoperative pain have not been extensively studied, especially in children. This study was to investigate whether there would be an association between the four major ABO blood groups and postoperative pain, as indicated by the differences in pain scores and rescue fentanyl requirements among blood groups in children after adenotonsillectomy. Methods A total of 124 children, aged 3–7 years, ASA I or II, and undergoing elective adenotonsillectomy were enrolled in the study. Postoperative pain was evaluated using the Children’s Hospital of Eastern Ontario Pain Scale (CHEOPS) and the rescue fentanyl requirement in post anesthesia care unit (PACU) was analyzed. Pediatric Anesthesia Emergence Delirium (PAED) score and the duration of PACU were recorded. The postoperative nausea and vomiting (PONV) within 24 h were documented. Results Among four blood type groups, no significant differences were observed regarding surgery time, and the gaps of fentanyl given at the anesthesia induction and the first rescue fentanyl injection in PACU. However, patients from AB and B blood groups had significantly higher pain score at initial CHEOPS assessment and consequently, higher consumption of rescue fentanyl during PACU stay. A significantly higher percentage of patients had received > 1 μg/kg rescue fentanyl. Higher PAED scores were also observed in AB and B blood groups. Conclusion Paediatric patients with AB and B blood type had higher postoperative CHEOPS pain score and required significantly more fentanyl for pain control than those with A and O blood type after T&A. The initial scores of PAED in patients with AB and B blood type were also higher than that in patients with A and O blood type.

Prenatal exposure to anesthetics has raised increasing attention about the neuronal development in offspring. Animal models are usually used for investigation. As a new drug, esketamine is the s-isoform of ketamine and is twice as potent as the racemic ketamine with less reported adverse effects. Esketamine is currently being used and become more favorable in clinical anesthesia work, including surgeries during pregnancy, yet the effect on the offspring is unknown. The present study aimed to elucidate the effects of gestational administration of esketamine on neuronal development in offspring, using a rat model. Gestational day 14.5 pregnant rats received intravenous injections of esketamine. The postnatal day 0 (P0) hippocampus was digested and cultured in vitro to display the neuronal growth morphology. On Day 4 the in vitro experiments revealed a shorter axon length and fewer dendrite branches in the esketamine group. The results from the EdU- imaging kit showed decreased proliferative capacity in the subventricular zone (SVZ) and dentate gyrus (DG) in both P0 and P30 offspring brains in the esketamine group. Moreover, neurogenesis, neuron maturity and spine density were impaired, resulting in attenuated long-term potentiation (LTP). Compromised hippocampal function accounted for the deficits in neuronal cognition, memory and emotion. The evidence obtained suggests that the neurobehavioral deficit due to prenatal exposure to esketamine may be related to the decrease phosphorylation of CREB and abnormalities in N-methyl- d -aspartic acid receptor subunits. Taken together, these results demonstrate the negative effect of prenatal esketamine exposure on neuronal development in offspring rats. Graphical Abstract G14.5 esketamine administration influenced the neurobehavior of the offspring in adolescence. Poorer neuronal growth and reduced brain proliferative capacity in late gestation and juvenile pups resulted in impaired P30 neuronal plasticity and synaptic spines as well as abnormalities in NMDAR subunits. Attenuated LTP reflected compromised hippocampal function, as confirmed by behavioral tests of cognition, memory and emotions. This figure was completed on the website of Figdraw.

This study aimed to investigate patients' expectative pain of spinal anesthesia puncture and anxiety pre-anesthesia, and to examine the effect of lidocaine-prilocaine cream and remimazolam prior to spinal anesthesia puncture on pain relief and anxiety release. Patients undergoing spinal anesthesia were divided into control, lidocaine-prilocaine cream, and lidocaine-prilocaine cream with remimazolam groups. A questionnaire consisting of The Amsterdam Preoperative Anxiety and Information Scale (APAIS) and patient's concerns and Visual Analog Scale (VAS) was used to evaluate patient's anxiety and pain. The primary outcomes were differences in VAS and anxiety scores. Patient's spinal anesthesia-related concerns, advent events and hemodynamic index were also recorded. The expected spinal anesthesia puncture pain was 5.34±0.27 and anxiety scores before spinal anesthesia was 10.88 ± 0.64. A statistically significant positive correlation of 31.3% was detected between VAS and APAIS scores (r = 0.313; P=0.003). The VAS score at the time of puncture decreased by 29.7% (3.78±0.40, P=0.001) in lidocaine-prilocaine cream group and 29.2% (3.75±0.39, P=0.001) in lidocaine-prilocaine cream with remimazolam group compared with the expected VAS score. Lidocaine-prilocaine cream combined with or without remimazolam reduced the percentage of moderate pain (21.4% and 31.3% vs 50.0%, P=0.0001) and increased mild pain (60.7% vs 59.4% vs 22.7%, P=0.03). Anxiety score in lidocaine-prilocaine cream group was reduced by 2.84 (8.04±0.76 vs 10.88 ± 0.46, P=0.05) when compared with pre-anesthesia. Concerns about postoperative pain (P=0.03) and fear of the needle or intervention (P=0.000) both decreased post-anesthesia among groups. Approximately half of the patients scheduled for spinal anesthesia experienced a moderate level of preoperative anxiety. The patient's pain expectation from the spinal anesthesia puncture was moderate, which was higher than the actual pain. Lidocaine-prilocaine cream with or without remimazolam sedative before spinal anesthesia puncture reduced the patient's pain and anxiety scores after surgery.

Discovery of thermoelectric materials has long been realized by the Edisonian trial and error approach. However, recent progress in theoretical calculations, including the ability to predict structures of unknown phases along with their thermodynamic stability and functional properties, has enabled the so-called inverse design approach. Compared to the traditional materials discovery, the inverse design approach has the potential to substantially reduce the experimental efforts needed to identify promising compounds with target functionalities. By adopting this approach, here we have discovered several unreported half-Heusler compounds. Among them, the p-type TaFeSb-based half-Heusler demonstrates a record high ZT of ~1.52 at 973 K. Additionally, an ultrahigh average ZT of ~0.93 between 300 and 973 K is achieved. Such an extraordinary thermoelectric performance is further verified by the heat-to-electricity conversion efficiency measurement and a high efficiency of ~11.4% is obtained. Our work demonstrates that the TaFeSb-based half-Heuslers are highly promising for thermoelectric power generation. The discovery of thermodynamically stable thermoelectric materials for power generation has relied on empirical methods that were not effective. Here, the authors apply the inverse design approach to identify and experimentally realize TaFeSb-based half Heuslers with high thermoelectric performance.

Groundwater resource is significantly important for sustainable development of the world, especially for arid endorheic watersheds. A total of 28 groundwaters were collected for hydrogeochemical analysis from the arid Chaka watershed on Tibetan plateau to illustrate the hydrochemical evolution, formation mechanisms and feasibility of groundwater in small arid endorheic watersheds where groundwater is much scarcer. The results showed groundwater has a slightly alkaline nature, and varies from soft fresh HCO 3 -Ca type to hard brackish/saline Cl-Na type along the groundwater flow path in the watershed with the total hardness in the range of 270–2,127 mg/L and the total dissolved solids in the range of 282–41,770 mg/L. Nitrogen and fluoride in phreatic water are found sporadically exceeding the permissible limits with the maximum value of 118 mg/L for nitrate, 1.2 mg/L for ammonia and 1.2 mg/L for fluoride. Hydrochemistry of phreatic and confined groundwater is naturally governed by water-rock interactions including minerals (halite, gypsum and anhydrite) dissolution, silicate weathering and cation-exchange reaction. The salinity of phreatic water is also dominantly controlled by the strong evaporation. Human activity is one of the important mechanisms influencing the hydrochemical signature of groundwater regardless of the depth. Groundwater has a great hydrogeochemical discrepancy spatially across the watershed and varies from excellent to extremely poor quality in phreatic aquifers. A better water quality that under the good to medium categories was observed in the confined aquifers with 80% of samples having the EWQI value less than 100 and others in the range of 100–150. Phreatic groundwater away from the river and in the downstream area has a relatively poor quality for domestic and agricultural purposes, and should be avoided to direct utilization. This research can improve the understanding of groundwater hydrogeochemical feature, genesis, and its constraints on the availability and feasibility of groundwater resources in small arid watersheds worldwide.

Clear cell renal cell carcinoma (ccRCC) is the most common kidney malignancy, with a poor prognosis for advanced-stage patients. Identifying key biomarkers involved in tumor progression is crucial for improving treatment outcomes. In this study, we employed an integrated approach combining single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq) to identify biomarkers associated with ccRCC progression and prognosis. Single-cell transcriptomic data were obtained from publicly available datasets, and genes related to tumor progression were screened using Monocle2. Bulk RNA-seq data for ccRCC were retrieved from The Cancer Genome Atlas (TCGA) and integrated with scRNA-seq data to explore tumor heterogeneity. We identified 3 beta-hydroxy steroid dehydrogenase type 7 (HSD3B7) as a candidate biomarker for ccRCC, associated with poor overall survival, disease-specific survival, and progression-free interval. Elevated HSD3B7 expression correlated with aggressive clinical features such as advanced TNM stages, histologic grades, and metastasis. Functional studies demonstrated that HSD3B7 promotes cell proliferation, migration, and invasion in vitro, while its silencing significantly inhibits tumor growth in vivo. Our findings reveal that HSD3B7 is a novel biomarker for ccRCC, providing insights into its role in tumor progression and potential as a target for therapy. This study highlights the value of integrating scRNA-seq and bulk RNA-seq data to uncover key regulators of tumor biology and lays the foundation for developing personalized therapeutic strategies for ccRCC patients.

Purpose Previous randomized studies have shown a survival benefit of using regorafenib but a high rate of adverse events in unresectable colorectal cancer patients. To reduce these adverse events and improve the tolerability, we examined the appropriate dose of regorafenib based on body weight. Methods We used a nationwide claims database in Japan and examined the efficacy and safety of regorafenib for patients with metastatic colorectal cancer between groups divided by body weight (60 kg) and median average dose (120 mg) between 2013 and 2018. We also assessed overall survival (OS) and adverse events between these groups. Results We identified 2530 Japanese patients (heavy weight/high dose: 513, light weight/low dose: 921, heavy weight/low dose: 452, and light weight/high dose: 644). There was no significant difference in the adverse events and OS after inverse probability treatment weighting (IPTW) adjustment between heavy weight/high dose group and light weight/low dose group (hazard ratio, HR=0.97). Among the light-weight patients, higher average dose was associated with shorter OS (IPTW adjusted HR=1.21, 95% CI 1.05 – 1.39, Table 3 ) while among the heavy-weight patients, there was no significant difference in OS between high and low dose groups (IPTW adjusted HR=1.14, 95% CI 0.95 – 1.37). Conclusion The findings suggest that a low dose of regorafenib for light-weight patients may be as safe and effective as high doses for heavy-weight patients. Further studies should be conducted to identify an appropriate dose based on each patient's physique and condition.