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Abstract Neurotoxic effects of general anesthetics, particularly sevoflurane, on pediatric neurodevelopment are a global concern. This study investigated the molecular and metabolic impacts of repeated short exposures to sevoflurane in neonatal rats. Metabolomics analysis revealed significant changes in fatty acid and mitochondrial energy metabolism. Transcriptomic analysis identified altered gene expression related to neurodevelopment and mitochondrial function. Various analyses emphasized upregulation in oxidative phosphorylation and DNA repair pathways. Weighted gene co-expression network analysis (WGCNA) identified key gene modules associated with sevoflurane exposure. Despite these acute changes, no significant long-term memory impairments were detected. These findings highlight the impact of sevoflurane on mitochondrial energy metabolism, oxidative stress, and neuroinflammation, emphasizing its relevance to pediatric neurodevelopment. The absence of substantial long-term memory impairments provides insights into the safety and implications of sevoflurane use in pediatric anesthesia, calling for further research.

Abstract Background Sleep disturbance is linked to neurodegenerative diseases and the related brain pathophysiology. Serum neurofilament light chain (NfL) is a reliable biomarker for neurological disorders. This study examined the association between sleep characteristics and serum NfL levels in American adults. Methods In this cross-sectional study, data from the 2013–2014 US National Health and Nutrition Examination Survey were utilized. Participants were categorized into short (≤ 6 h), normal (7–8 h), and long (≥ 9 h) sleep groups based on their self-reported sleep durations. Sleep duration, trouble sleeping, and diagnosed sleep disorders were queried, forming “sleep pattern (healthy, moderate, and poor).” The association between sleep characteristics and serum NfL levels was assessed using multivariate linear regression models. Stratification and sensitivity analyses were conducted to determine the stability of results. Results Overall, 1637 participants were included; among them, 48.2% were male and 51.8% were female (mean ± SD, age: 46.9 ± 15.5 years) and 38.8% reported sleeping for ≤ 6 h, 54.4% for 7–8 h, and 6.8% for ≥ 9 h. Participants with longer sleep duration, poor sleep pattern, diagnosed sleep disorders, or trouble sleeping exhibited higher serum NfL levels. A positive correlation was found between extended sleep and elevated serum NfL levels (Adjusted β = 4.82, 95%CI: 2.2, 7.44, P

Abstract Background Off-label intranasal administration of injectable dexmedetomidine has been widely applied in the pediatric sedation setting. However, the development of an improved drug delivery system that is easy to use is needed. We developed a novel dexmedetomidine nasal spray that can be administered directly without dilution or configuration for pediatric pre-anesthetic sedation. This nasal spray has a fixed dose and is stable during storage. To the best of our knowledge, this is the first licensed nasal spray preparation of dexmedetomidine worldwide. Objective To evaluate the pre-anesthetic sedation efficacy and safety of the novel dexmedetomidine nasal spray in children. Methods The study was conducted at 11 sites in China between 24 November 2021 and 20 May 2022 and was registered in ClinicalTrials.gov (NCT05111431, first registration date: 20/10/2021). Subjects (n = 159) between 2 and 6 years old who were to undergo elective surgery were randomized to the dexmedetomidine group (n = 107) or the placebo group (n = 52) in a 2:1 ratio. The dosage was 30 µg or 50 µg based on the stratified body weight. The primary outcome measure was the proportion of subjects who achieved the desired child-parent separation and Ramsay scale ≥ 3 within 45 min of administration. Safety was monitored via the assessments of adverse events, blood pressure, heart rate, respiratory rate and blood oxygen saturation. Results The proportion of subjects achieving desired parental separation and Ramsay scale ≥ 3 within 45 min was significantly higher in the dexmedetomidine group (94.4%) vs the placebo group (32.0%) (P

Abstract Purpose No study has compared 30-day and 90-day adverse postoperative outcomes between old-age patients with and those without sarcopenia. Patients and methods We categorize elderly patients receiving major surgery into two groups according to the presence or absence of preoperative sarcopenia that were matched at a 1:4 ratio through propensity score matching (PSM). We analyzed 30-day or 90-day adverse postoperative outcomes and mortality in patients with and without sarcopenia receiving major surgery. Results Multivariate logistic regression analyses revealed that the patients with preoperative sarcopenia were at significantly higher risk of 30-day postoperative mortality (adjusted odds ratio [aOR]. = 1.25; 95% confidence interval [CI]. = 1.03–1.52) and 30-day major complications such as postoperative pneumonia (aOR = 1.15; 95% CI = 1.00-1.40), postoperative bleeding (aOR = 2.18; 95% CI = 1.04–4.57), septicemia (aOR = 1.31; 95% CI = 1.03–1.66), and overall complications (aOR = 1.13; 95% CI = 1.00-1.46). In addition, surgical patients with sarcopenia were at significantly higher risk of 90-day postoperative mortality (aOR = 1.50; 95% CI = 1.29–1.74) and 90-day major complications such as pneumonia (aOR = 1.27; 95% CI = 1.10–1.47), postoperative bleeding (aOR = 1.90; 95% CI = 1.04–3.48), septicemia (aOR = 1.52; 95% CI = 1.28–1.82), and overall complications (aOR = 1.24; 95% CI = 1.08–1.42). Conclusions Sarcopenia is an independent risk factor for 30-day and 90-day adverse postoperative outcomes such as pneumonia, postoperative bleeding, and septicemia and increases 30-day and 90-day postoperative mortality among patients receiving major surgery. Condensed abstract No study has compared 30-day and 90-day adverse postoperative outcomes between patients with and those without sarcopenia. We conducted a propensity score?matched (PSM) population-based cohort study to investigate the adverse postoperative outcomes and mortality in patients undergoing major elective surgery with preoperative sarcopenia versus those without preoperative sarcopenia. We demonstrated that sarcopenia is an independent risk factor for 30-day and 90-day adverse postoperative outcomes, such as postoperative pneumonia, bleeding, septicemia, and mortality after major surgery. Therefore, surgeons and anesthesiologists should attempt to correct preoperative sarcopenia, swallowing function, and respiratory muscle training before elective surgery to reduce postoperative complications that contribute to the decrease in surgical mortality.

Background Inadequate postoperative analgesia is associated with increased risks of various postoperative complications, longer hospital stay, decreased quality of life and higher costs.Objectives This study aimed to investigate the risk factors for moderate-to-severe postoperative pain within the first 24 hours and 24–48 hours after major hepatobiliary pancreatic surgery.Methods Data of patients who underwent surgery at the Department of Hepatobiliary Surgery in Henan Provincial People’s Hospital were collected from January 2018 to August 2020. Univariate and multivariate logistic regression analyses were used to identify the risk factors of postoperative pain.Results In total, 2180 patients were included in the final analysis. 183 patients (8.4%) suffered moderate-to-severe pain within 24 hours after operation. The independent risk factors associated with moderate-to-severe pain 24 hours after procedures were younger age (OR, 0.97; 95% CI 0.95 to 0.98, p

Objectives To explore the relationship between age and postoperative 24-hour moderate-to-severe pain after radical resection of lung cancer and the specific effect of moderate-to-severe pain in the post-anaesthesia care unit (PACU) on this relationship.Design Retrospective cohort study.Setting Single medical centre.Participants Patients ≥18 years having radical resection of lung cancer between 2018 and 2020.Measurements Postoperative 24-hour moderate-to-severe pain.Results A total of 3764 patients were included in the analysis. The incidence of postoperative 24-hour moderate-to-severe pain was 28.3%. Age had a significant effect on the prediction model of postoperative 24-hour moderate-to-severe pain. Among the whole population and those without moderate-to-severe pain in the PACU, those who were younger than 58.5 years were prone to experience moderate-to-severe pain 24 hours after surgery, and in patients with moderate-to-severe pain in the PACU, the age threshold was 62.5 years.Conclusion For patients who underwent elective radical resection for lung cancer, age was related to postoperative 24-hour moderate-to-severe pain, and moderate-to-severe pain in the PACU had a specific effect on this relationship. Patients among the whole population and those patients without moderate-to-severe pain in the PACU were more likely to experience postoperative 24-hour moderate-to-severe pain when they were younger than 58.5 years old, and in patients with moderate-to-severe pain in the PACU, the age threshold was 62.5 years old.

Safflower is a valuable medicinal plant due to its diverse flavonoids, known as safflower yellow (SY) and safflower red (SR) pigments, which are popular in the fields of medicine, food and natural dyes. The main pharmacological ingredient in safflower is SY pigment, which is a kind of water-soluble flavonoid, such as hydroxysafflor yellow A (HSYA). In contrast, SR pigment mainly contains carthamin, which is sparingly soluble in water and has a historic reputation as a red colorant. These flavonoids from both SY and SR pigments belong to C-glucosylquinochalcones and their derivatives, which only exist in safflower. Over the past few decades, genetics, molecular biology and multi-omics strategies have been used to study flavonoid biosynthesis in safflower. However, there has not been a comprehensive summary of the application and molecular progress of safflower flavonoid biosynthesis. In this review, we summarize the various applications of safflower in medicine, natural dyes, and food, as well as the molecular regulation of flavonoid biosynthesis. We also propose future research directions on safflower flavonoids. This work aims to provide an objective national and international review of literature on the application and biosynthetic regulation of safflower flavonoids.

Eukaryotic genomes are hierarchically packaged into cell nucleus, affecting gene regulation. The genome is organized into multiscale structural units, including chromosome territories, compartments, topologically associating domains (TADs), and DNA loops. The identification of these hierarchical structures has benefited from the development of experimental approaches, such as 3C-based methods (Hi-C, ChIA-PET, etc.), imaging tools (2D-FISH, 3D-FISH, Cryo-FISH, etc.) and ligation-free methods (GAM, SPRITE, etc.). In recent two decades, numerous studies have shown that the 3D organization of genome plays essential roles in multiple cellular processes via various mechanisms, such as regulating enhancer activity and promoter-enhancer interactions. However, there are relatively few studies about the 3D genome in livestock species. Therefore, studies for exploring the function of 3D genomes in livestock are urgently needed to provide a more comprehensive understanding of potential relationships between the genome and production traits. In this review, we summarize the recent advances of 3D genomics and its biological functions in human and mouse studies, drawing inspiration to explore the 3D genomics of livestock species. We then mainly focus on the biological functions of 3D genome organization in muscle development and its implications in animal breeding.

Abstract Background Although the molecular features of pancreatic ductal adenocarcinoma (PDAC) have been well described, the impact of detailed gene mutation subtypes on disease progression remained unclear. This study aimed to evaluate the impact of different TP53 mutation subtypes on clinical characteristics and outcomes of patients with PDAC. Methods We included 639 patients treated with PDAC in Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine between Jan 2019 and Jun 2021. The genomic alterations of PDAC were analyzed, and the association of TP53 mutation subtypes and other core gene pathway alterations with patients’ clinical characteristics were evaluated by Chi-squared test, Kaplan-Meier method and Cox regression model. Results TP53 missense mutation was significantly associated with poor differentiation in KRASmut PDAC (50.7% vs. 36.1%, P = 0.001). In small-sized (≤ 2 cm) KRASmut tumors, significantly higher LNs involvement (54.8% vs. 23.5%, P = 0.010) and distal metastic rate (20.5% vs. 2.9%, P = 0.030) were observed in those with TP53 missense mutation instead of truncating mutation. Compared with TP53 truncating mutation, missense mutation was significantly associated with reduced DFS (6.6 [5.6–7.6] vs. 9.2 [5.2–13.3] months, HR 0.368 [0.200–0.677], P = 0.005) and OS (9.6 [8.0-11.1] vs. 18.3 [6.7–30.0] months, HR 0.457 [0.248–0.842], P = 0.012) in patients who failed to receive chemotherapy, while higher OS (24.2 [20.8–27.7] vs. 23.8 [19.0–28.5] months, HR 1.461 [1.005–2.124], P = 0.047) was observed in TP53missense cases after chemotherapy. Conclusions TP53 missense mutation was associated with poor tumor differentiation, and revealed gain-of-function properties in small-sized KRAS transformed PDAC. Nonetheless, it was not associated with insensitivity to chemotherapy, highlighting the neoadjuvant therapy before surgery as the potential optimized strategy for the treatment of a subset of patients.

Abstract Sequence stratigraphy study in mudstone and oil shale strata is difficulty but critical for the analysis of the quality unconventional oil and gas reservoirs. This contribution investigates the sequence stratigraphy of the Eocene thick organic-rich fine-grained sediments in the Fushun basin, according to the organic geochemical data measured in laboratory and predicted by the amplitude difference the resistivity and the density curve when they are overlapping (which was called ΔlogR). The sampling interval of ΔlogR was 0.125 m. The results show that the total organic carbon, the oil yield, and the petroleum potential of the Eocene mudstones prove a good linear correlation between values measured in lab and values predicted by the ΔlogR model. A total of 21 parasequences are identified in mudstones and can be divided into two cycles, a fully developed lower cycle and an underdeveloped upper cycle. There are four organic matter accumulation stages in a fully developed cycle, including two stages in the uprising half-cycle characterized by low values and rising values of the predicted geochemical data, respectively, followed by two stages in the declining half cycle characterized by high values and decreasing values of the predicted geochemical data, respectively. This contribution provides a basis for a further analysis of the characteristics of organic matter cycles in the oil shale strata of the Fushun Basin and areas with similar situation.

Abstract. Introduction:. This study investigates the association between chronic postsurgical pain (CPSP) and long-term postsurgical analgesic usage in patients undergoing neuraxial anesthesia, with a specific focus on the presence or absence of sarcopenia. Objectives:. To assess the rate of analgesic prescription, including opioids, at 3 and 6 months postsurgery for patients with and without preoperative sarcopenia, and to determine the impact of sarcopenia on analgesic use after neuraxial anesthesia surgery. Methods:. Patients undergoing surgery under neuraxial anesthesia were categorized into sarcopenic and nonsarcopenic groups based on preoperative diagnosis using the ICD-10-CM code M62.84. Propensity score matching in a 1:4 ratio was applied for group matching. Analgesic prescription rates were evaluated at 3 and 6 months postsurgery, and multivariable logistic regression was used to analyze analgesic use, comparing patients with and without preoperative sarcopenia. Results:. Among 3805 surgical patients, 761 had sarcopenia, while 3044 did not. At 3 months postsurgery, 62.3% of sarcopenic patients received analgesics, with 2.9% receiving opioids, compared to 57.1% of nonsarcopenic patients receiving analgesics and 0.8% receiving opioids. At 6 months postsurgery, 30.8% of sarcopenic patients received analgesics (1.7% opioids), while 26.3% of non-sarcopenic patients received analgesics (0.3% opioids). Multivariable logistic regression analysis revealed that preoperative sarcopenia was significantly associated with higher analgesic prescription rates at both 3 months (adjusted odds ratio [aOR], 1.27; 95% confidence interval [CI], 1.05–1.53) and 6 months (aOR, 1.17; 95% CI, 1.07–1.42) postsurgery. Furthermore, sarcopenic patients exhibited significantly higher opioid prescription rates at 3 months (aOR, 1.11; 95% CI, 1.05–2.45) and 6 months (aOR, 1.89; 95% CI, 1.12–4.96) postsurgery. Conclusion:. Sarcopenia emerges as an independent risk factor for prolonged analgesic use after neuraxial anesthesia surgery and significantly elevates the risk of developing CPSP.

The hydrodynamics of the flow around piers affects the motion of ships navigating near these structures, while the motion of the ships, in turn, affects the distribution of the flow field near the piers. This study investigates the forces exerted on a ship in various ship–pier transverse distances using commercial computational fluid dynamics (CFD) software, Fluent 13.0, based on the RNG k-ε model, complemented by experiments with a physical model. The interaction between the ship’s motion and the flow field near the piers was considered. The results indicate that during the encounter between the ship and the pier, the boundary of the approaching ship affects the flow field near the pier, thereby affecting the generation and detachment of vortices behind the pier. The yaw moment of the ship demonstrates a marked “positive peak–negative peak–positive peak” pattern. Moreover, as the ship–pier transverse distance increases, the impact of the pier on the ship’s motion decreases, and it becomes negligible when the distance reaches 0.9 times the diameter of the pier (D), suggesting that the pier has a minimal impact on ship navigation if the ship–pier transverse distance exceeds this threshold.

PurposeA retrospective cohort study was performed to determine the effect of nerve block on the incidence of postoperative mortality in patients with hip replacement.MethodsAccording to the inclusion and exclusion criteria, patients who were undergoing hip replacement for the first time under general or intraspinal anesthesia, classified as ASA class I–IV, and aged ≥65 years were selected. We collected the general data, past medical history, preoperative laboratory test results, perioperative fluid intake and outflow data, perioperative anesthesia and related drug data, postoperative laboratory results, and correlation time index. Patients with preoperative combined nerve block were included in the N group, and those without combined nerve block were included in the NN group. The patients were followed up via telephone call to assess survival outcomes at 3 years after surgery. Propensity score matching and uni- and multivariate analyses were performed to determine the influence of nerve block and other related factors on postoperative mortality.ResultsA total of 743 patients were included in this study, including 262 in the N group and 481 in the NN group. Two hundred five patients in both groups remained after propensity score matching. Main result: Preoperative nerve block was associated with reduced mortality three years after surgery.ConclusionNerve block reduces the incidence of 3-year postoperative mortality, and composite nerve block with general anesthesia and neuraxial anesthesia is worthy of promotion.

Introduction: Postoperative nausea and vomiting (PONV) is a prevalent postsurgical complication. The objective of our study was to compare the effect of different doses of dexmedetomidine on PONV in female patients undergoing radical thoracoscopic lung cancer resection.Methods: A total of 164 female patients undergoing elective thoracoscopic radical lung cancer surgery were enrolled and assigned to one of four groups. Patients received 0.2 μg/kg/h, 0.4 μg/kg/h, 0.8 μg/kg/h dexmedetomidine and normal saline in the Dex1, Dex2, Dex3 and Control groups, respectively. The primary outcome was the incidence of PONV during 48 h postoperatively. The second outcomes included the incidence of PONV and postoperative vomiting (POV) at four time points postoperatively (T1: PACU retention period; T2: PACU discharge to postoperative 12 h; T3: postoperative 12 h-postoperative 24 h; T4: postoperative 24 h-postoperative 48 h), the area under the curve of PONV grade (PONVAUC), PONV grade, POV grade and other postoperative recovery indicators.Results: The incidence of PONV differed among the four groups. The Dex2 group (29.27%) was lower than that in the Dex1 group (61.90%) and Control group (72.50%). The incidence of PONV at T2 in the Dex1 group (11.90%) and Dex2 group (9.76%) was lower than that in the Control group (42.50%). The incidence of PONV at T3 in the Dex2 group (29.27%) was lower than that in the Dex1 group (61.90%) and Control group (62.50%). The PONVAUC was lower in the Dex2 group than in the Control group. The incidence of POV at T3 in the Dex2 and Dex3 groups was lower than that in the Control group. The consumption of remifentanil, norepinephrine, PACU dwell time, VAS scores, postoperative PCA press frequency, and the time for the first postoperative oral intake were different among the four groups. The regression model shows that the Dex2 group is a protective factor for PONV.Conclusion: Dexmedetomidine can reduce the incidence of PONV and accelerate postoperative recovery in female patients undergoing radical thoracoscopic lung cancer resection. Compared with the other two dosages, 0.4 μg/kg/h dexmedetomidine is preferable.Clinical Trial Registration:chictr.org.cn, identifier ChiCTR2300071831

Abstract Purpose To investigate the dose-dependent protective effects of statins, specific classes of statins, and different intensities of statin use on sepsis risk in patients with type 2 diabetes mellitus (T2DM). Methods We included patients with T2DM aged ≥ 40 years. Statin use was defined as the use of statin on most days for > 1 months with a mean statin dose of ≥ 28 cumulative defined daily doses (cDDDs) per year (cDDD-year). An inverse probability of treatment-weighted Cox hazard model was used to investigate the effects of statin use on sepsis and septic shock while considering statin use status as a time-dependent variable. Results From 2008 to 2020, a total of 812 420 patients were diagnosed as having T2DM. Among these patients, 118,765 (27.79%) statin nonusers and 50 804 (12.03%) statin users developed sepsis. Septic shock occurred in 42,755 (10.39%) individuals who did not use statins and 16,765 (4.18%) individuals who used statins. Overall, statin users had a lower prevalence of sepsis than did nonusers. The adjusted hazard ratio (aHR) of statin use was 0.37 (95% CI 0.35, 0.38) for sepsis compared with no statin use. Compared with the patients not using statins, those using different classes of statins exhibited a more significant reduction in sepsis, with aHRs (95% CIs) of sepsis being 0.09 (0.05, 0.14), 0.32 (0.31, 0.34), 0.34 (0.32, 0.36), 0.35 (0.32, 0.37), 0.37 (0.34, 0.39), 0.42 (0.38, 0.44), and 0.54 (0.51, 0.56) for pitavastatin, pravastatin, rosuvastatin, atorvastatin, simvastatin, fluvastatin, and lovastatin use, respectively. In the patients with different cDDD-years of statins, multivariate analysis indicated a significant reduction in sepsis, with aHRs of 0.53 (0.52, 0.57), 0.40 (0.39, 0.43), 0.29 (0.27, 0.30), and 0.17 (0.15, 0.19) for Q1, Q2, Q3, and Q4 cDDD-years (P for trend

Abstract Background Combining oxygen facemask with apnoeic oxygenation using high-flow-nasal-oxygen (HFNO) for preoxygenation in the operating room has not been studied against standard oxygen facemask alone. We hypothesized that facemask-alone would be associated with lower levels of lowest end-tidal oxygen (EtO2) within 2 min after intubation in comparison with facemask combined with HFNO. Methods In an international prospective before–after multicentre study, we included adult patients intubated in the operating room from September 2022 to December 2022. In the before period, preoxygenation was performed with facemask-alone, which was removed during laryngoscopy. In the after period, facemask combined with HFNO was used for preoxygenation and HFNO for apnoeic oxygenation during laryngoscopy. HFNO was maintained throughout intubation. The primary outcome was the lowest EtO2 within 2 min after intubation. The secondary outcome was SpO2 ≤ 95% within 2 min after intubation. Subgroup analyses were performed in patients without and with obesity. This study was registered 10 August 2022 with ClinicalTrials.gov, number NCT05495841. Results A total of 450 intubations were evaluated, 233 with facemask-alone and 217 with facemask combined with HFNO. In all patients, the lowest EtO2 within 2 min after intubation was significantly lower with facemask-alone than with facemask combined with HFNO, 89 (85–92)% vs 91 (88–93)%, respectively (mean difference − 2.20(− 3.21 to − 1.18), p

Abstract Background The study aims to clarify the association of sarcopenia with perioperative and postoperative complications in oral cavity squamous cell carcinoma (OCSCC) patients undergoing curative surgery and to understand the reasons causing the poor oncologic outcomes for OCSCC. Methods We conducted a propensity score matching study to investigate the association of perioperative and postoperative outcomes in OCSCC patients with sarcopenia and without sarcopenia. A retrospective analysis of a large national data set from the Taiwan Cancer Registry Database was conducted. At least two claims for patients with a principal diagnosis of sarcopenia within the 12‐month preoperative period were defined as the criteria for sarcopenia diagnosis (ICD‐10‐CM code M62.84). Sarcopenia was diagnosed through the measurement of low muscle strength and low muscle mass by any one of the patient's attending orthopaedic physician, rehabilitation physician, family medicine specialist or geriatrician. A multivariate logistic regression model was used to calculate the perioperative, and postoperative major complications. Results Our final cohort included 16 293 patients with OCSCC (10 862 and 5 431 in the sarcopenia and nonsarcopenia groups, respectively) who were eligible for further analysis. The sarcopenia group was 10.40% female and 89.60% male, and the nonsarcopenia group was 9.74% female and 90.26% male. The mean age ± standard deviation (SD) were 56.44 ± 11.14 and 56.22 ± 11.29 for sarcopenia and nonsarcopenia groups. OCSCC patients with sarcopenia undergoing curative surgery had a significantly higher blood transfusion rate and volume; longer intensive care unit (ICU) stay, and hospital stay; higher postoperative 30‐day mortality (adjusted odds ratio [aOR]: 1.12, 95% confidence interval [CI] [1.07, 1.56]) and rates of pneumonia (aOR: 1.34, 95% CI [1.20, 1.50]), acute renal failure (aOR: 1.45, 95% CI [1.12, 1.87]) and septicaemia (aOR: 1.29, 95% CI [1.15, 1.45]); higher postoperative first‐year mortality (aOR: 1.18, 95% CI [1.13, 1.51]) and rates of pneumonia (aOR: 1.43, 95% CI [1.30, 1.56]), acute myocardial infarction (aOR: 1.52, 95% CI [1.06, 2.18]) and septicaemia (aOR: 1.29, 95% CI [1.15, 1.45]). Conclusions OCSCC patients with sarcopenia might exhibit more perioperative and surgical complications than those without sarcopenia.

The commercial exploitation of unconventional petroleum resources (e.g., shale oil/gas and tight oil/gas) has drastically changed the global energy structure within the past two decades. Sweet-spot intervals (areas), the most prolific unconventional hydrocarbon resources, generally consist of extraordinarily high organic matter (EHOM) deposits or closely associated sandstones/carbonate rocks. The formation of sweet-spot intervals (areas) is fundamentally controlled by their depositional and subsequent diagenetic settings, which result from the coupled sedimentation of global or regional geological events, such as tectonic activity, sea level (lake level) fluctuations, climate change, bottom water anoxia, volcanic activity, biotic mass extinction or radiation, and gravity flows during a certain geological period. Black shales with EHOM content and their associated high-quality reservoir rocks deposited by the coupling of major geological events provide not only a prerequisite for massive hydrocarbon generation but also abundant hydrocarbon storage space. The Ordovician–Silurian Wufeng–Longmaxi shale of the Sichuan Basin, Devonian Marcellus shale of the Appalachian Basin, Devonian–Carboniferous Bakken Formation of the Williston Basin, and Triassic Yanchang Formation of the Ordos Basin are four typical unconventional hydrocarbon systems selected as case studies herein. In each case, the formation of sweet-spot intervals for unconventional hydrocarbon resources was controlled by the coupled sedimentation of different global or regional geological events, collectively resulting in a favorable environment for the production, preservation, and accumulation of organic matter, as well as for the generation, migration, accumulation, and exploitation of hydrocarbons. Unconventional petroleum sedimentology, which focuses on coupled sedimentation during dramatic environmental changes driven by major geological events, is key to improve the understanding of the formation and distribution of sweet-spot intervals (areas) in unconventional petroleum systems.

BackgroundPreoperative cognitive impairment (PCI) may increase the incidence of postoperative delirium (POD), yet screening for cognitive impairment is rarely performed. This study hypothesized that Mini-Cog for preoperative cognitive impairment screening predicts postoperative delirium.MethodsThe prospective observational study recruited 153 elderly patients presenting for elective thoracic surgery. Cognitive function of these patients was screened using Mini-Cog preoperatively. We considered that patients with Mini-Cog scores ≤ 3 had cognitive impairment. Delirium was assessed using the Short CAM scale on postoperative days 1–5.ResultsOf the 153 participants, 54 (35.3%) were assigned to the PCI group, and 99 (64.7%) were assigned to the Normal group. Place of residence, education level, and history of hypertension were significantly different between the two groups (P < 0.05). 51 (33.3%) patients developed POD. Multifactorial analysis revealed that PCI (OR = 2.37, P = 0.028), older age (OR = 1.13, P = 0.009), ASA grade III (OR = 2.75, P = 0.012), and longer duration of anesthesia (OR = 1.01, P = 0.007) were associated with POD.ConclusionPreoperative cognitive impairment is strongly associated with POD. Mini-Cog could be recommended for screening PCI.Clinical trial registrationClinicalTrials.gov, identifier NCT05798767.

Background: Difficult airway conditions represent a substantial challenge for clinicians. Predicting such conditions is essential for subsequent treatment planning, but the reported diagnostic accuracies are still quite low. To overcome these challenges, we developed a rapid, non-invasive, cost-effective, and highly-accurate deep-learning approach to identify difficult airway conditions through photographic image analysis. Methods: For each of 1000 patients scheduled for elective surgery under general anesthesia, images were captured from 9 specific and different viewpoints. The collected image set was divided into training and testing subsets in the ratio of 8:2. We used a semi-supervised deep-learning method to train and test an AI model for difficult airway prediction. Results: We trained our semi-supervised deep-learning model using only 30% of the labeled training samples (with the remaining 70% used without labels). We evaluated the model performance using metrics of accuracy, sensitivity, specificity, F1-score, and the area under the ROC curve (AUC). The numerical values of these four metrics were found to be 90.00%, 89.58%, 90.13%, 81.13%, and 0.9435, respectively. For a fully-supervised learning scheme (with 100% of the labeled training samples used for model training), the corresponding values were 90.50%, 91.67%, 90.13%, 82.25%, and 0.9457, respectively. When three professional anesthesiologists conducted comprehensive evaluation, the corresponding results were 91.00%, 91.67%, 90.79%, 83.26%, and 0.9497, respectively. It can be seen that the semi-supervised deep learning model trained by us with only 30% labeled samples can achieve a comparable effect with the fully supervised learning model, but the sample labeling cost is smaller. Our method can achieve a good balance between performance and cost. At the same time, the results of the semi-supervised model trained with only 30% labeled samples were very close to the performance of human experts. Conclusions: To the best of our knowledge, our study is the first one to apply a semi-supervised deep-learning method in order to identify the difficulties of both mask ventilation and intubation. Our AI-based image analysis system can be used as an effective tool to identify patients with difficult airway conditions. Clinical trial registration: ChiCTR2100049879 (URL: http://www.chictr.org.cn).

Summary: The cellular and molecular actions of general anesthetics to induce anesthesia state and also cellular signaling changes for subsequent potential “long term” effects remain largely elusive. General anesthetics were reported to act on voltage-gated ion channels and ligand-gated ion channels. Here we used single-cell RNA-sequencing complemented with whole-cell patch clamp and calcium transient techniques to examine the gene transcriptome and ion channels profiling of sevoflurane and propofol, both commonly used clinically, on the human fetal prefrontal cortex (PFC) mixed cell cultures. Both propofol and sevoflurane at clinically relevant dose/concentration promoted “microgliosis” but only sevoflurane decreased microglia transcriptional similarity. Propofol and sevoflurane each extensively but transiently (

Colorectal cancer (CRC) is the third most predominant malignancy in the world. Although the importance of immune system in cancer development has been well established, the underlying mechanisms remain to be investigated further. Here we studied a novel protein prokineticin 2 (Prok2, also known as Bv8) as a key pro-tumoral factor in CRC progression in in vitro and ex vivo settings. Human colorectal tumor tissues, myeloid cell lines (U937 cells and HL60 cells) and colorectal cancer cell line (Caco-2 cells) were used for various studies. Myeloid cell infiltration (especially neutrophils) and Bv8 accumulation were detected in human colorectal tumor tissue with immunostaining. The chemotactic effects of Bv8 on myeloid cells were presented in the transwell assay and chemotaxis assy. Cultured CRC cells treated with myeloid cells or Bv8 produced reactive oxygen species (ROS) and vascular endothelial growth factor (VEGF). Furthermore, ROS and VEGF acted as pro-angiogenesis buffer in myeloid cell-infiltrated CRC microenvironment. Moreover, myeloid cells or Bv8 enhanced energy consumption of glycolysis ATP and mitochondria ATP of CRC cells. Interestingly, myeloid cells increased CRC cell viability, but CRC cells decreased the viability of myeloid cells. ERK signalling pathway in CRC cells was activated in the presence of Bv8 or co-cultured myeloid cells. In conclusion, our data indicated the vital roles of Bv8 in myeloid cell infiltration and CRC development, suggesting that Bv8 may be a potential therapeutic target for colorectal cancer-related immunotherapy.

Abstract Osteoporosis (OP) has plagued many women for years, and bone density loss is an indicator of OP. The purpose of this study was to evaluate the relationship between the polymorphism of the rs7586085, CCDC170 and GALNT3 gene polymorphisms and the risk of OP in the Chinese Han population. Using the Agena MassArray method, we identified six candidate SNPs on chromosomes 2 and 6 in 515 patients with OP and 511 healthy controls. Genetic model analysis was performed to evaluate the significant association between variation and OP risk, and meanwhile, the multiple tests were corrected by false discovery rate (FDR). Haploview 4.2 was used for haplotype analysis. In stratified analysis of BMI ˃ 24, rs7586085, rs6726821, rs6710518, rs1346004, and rs1038304 were associated with the risk of OP based on the results of genetic models among females even after the correction of FDR (q d

Abstract The Late Ordovician mass extinction (LOME, ca. 445 Ma; Hirnantian stage) is the second most severe biological crisis of the entire Phanerozoic. The LOME has been subdivided into two pulses (intervals), at the beginning and the ending of the Hirnantian glaciation, the LOMEI-1 and LOMEI-2, respectively. Although most studies suggest a rapid cooling and/or oceanic euxinia as major causes for this mass extinction, the driver of these environmental changes is still debated. As other Phanerozoic’s mass extinctions, extensive volcanism may have been the potential trigger of the Hirnantian glaciation. Indirect evidence of intense volcanism comes from Hg geochemistry: peaks of Hg concentrations have been found before and during the LOME, and have all been attributed to global volcanism in origin. Here, we present high-resolution mercury (Hg) profiles in three study sections, from a shelf to slope transect, on the Yangtze Shelf Sea (South China) to address the origin of Hg anomalies across the Ordovician–Silurian (O–S) boundary. The results show Hg anomaly enrichments in the middle Katian, late Katian, the LOMEI-1 at the beginning of the Hirnantian glaciation, the LOMEI-2 in the late Hirnantian glaciation, and late Rhuddanian. The Hg anomaly enrichments during the middle–late Katian and late Rhuddanian would probably reflect a volcanic origin. We find two different controls on the recorded Hg anomalies during the extinction time: i.e., primarily volcanism for the Hg anomaly at the LOMEI-1 and euxinia for the Hg anomaly at the LOMEI-2. Expansion of euxinia at the LOMEI-1 would have been probably enhanced by volcanic fertilization via weathering of volcanic deposits during the Middle and late Katian, and combined with euxinia at the LOMEI-2 to finally be responsible for the two pulses of the LOME.

Abstract Background To date, no data on the effect of adjuvant postmastectomy radiotherapy (PMRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast invasive ductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF). Patients and methods We enrolled 646 women with left-breast IDC at clinical stages I–IIIC and HFrEF receiving radical total mastectomy (TM) followed by adjuvant PMRT or non-adjuvant PMRT. We categorized them into two groups based on their adjuvant PMRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score–weighted population to obtain hazard ratios (HRs). Results In the IPTW-adjusted model, adjuvant PMRT (adjusted HR [aHR]: 0.52; 95% confidence interval [CI]: 0.37–0.74) was a significant independent prognostic factor for all-cause death (P = 0.0003), and the aHR (95% CI) of LRR and DM for adjuvant PMRT was 0.90 (0.79–0.96; P = 0.0356) and 0.89 (0.54–1.50; P = 0.6854), respectively, compared with the nonadjuvant PMRT group. Conclusion Adjuvant PMRT was associated with a decrease in all-cause death, and LRR in women with left IDC and HFrEF compared with nonadjuvant PMRT.

Abstract Background Postpartum depression (PPD) is a common complication of cesarean section. S-ketamine given intravenously during surgery can help prevent PPD. However, whether S-ketamine in patient-controlled intravenous analgesia (PCIA) can reduce the incidence of PPD is unknown. This study assessed the effect of S-ketamine as an adjuvant in PCIA for preventing PPD in women undergoing cesarean delivery. Methods A total of 375 parturients scheduled to undergo cesarean section and then receive PCIA were recruited from a single center and were randomly assigned to control (C) group (sufentanil 2 μg/kg + tropisetron 10 mg) or S-ketamine (S) group (S-ketamine 0.5 mg/kg + sufentanil 2 μg/kg + tropisetron 10 mg). The primary outcome was the incidence of PPD measured by the Edinburgh postnatal depression scale (EPDS) after surgery. The secondary outcomes were EPDS scores, visual analog scale (VAS) scores, Ramsay sedation scale (RSS) scores, and the rate of adverse events, including headache, nausea, dizziness, drowsiness, and vomit. Results A total of 275 puerperal women were included in the study. The rate of depression in parturient on postoperative days 3, 14, 28 in the C group and S group were 17.6 and 8.2% (p

BackgroundNow the occurrence of delirium is more concerning to clinicians and psychiatrists. It has been reported that vitamin D deficiency may be a relevant factor in the development of delirium in hospitalized patients.Study objectiveTo investigate the association between vitamin D concentration and delirium in hospitalized patients.DesignMeta-analysis.MethodsA systematic literature search was conducted using PubMed, EMBASE, and the Cochrane Library. The primary outcome was the occurrence of delirium in the inpatient setting. Odds ratios (OR) were calculated with random or fixed effects models.ResultsIn this article, we define the normal range of vitamin D concentrations as greater than 75 nmol / L, 50-75 nmol / L as vitamin D insufficiency, 25-50 nmol / L as vitamin D deficiency, and less than 25 nmol / L as vitamin D severe deficiency. The Results showed that severe vitamin D deficiency (OR: 1.98 [1.41-2.79], PConclusionCompared with normal vitamin D levels, severe vitamin D deficiency and vitamin D deficiency, but not vitamin D insufficiency, are associated with a higher incidence of delirium in hospitalized patients.Trial registrationThis review was registered in the PROSPERO database under identifier CRD42021271347. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021271347.

Summary: Background: Whether the route of anaesthesia is an independent risk factor for dementia remains unclear. Therefore, we conducted a propensity score–matched (PSM) population-based cohort study to compare dementia incidence among surgical patients undergoing different routes of anaesthesia. Methods: The inclusion criteria were being an inpatient >20 years of age who underwent major elective surgery, defined as those requiring GA without or with inhalation anaesthetics or regional anaesthesia, and being hospitalised for >1 day between Jan 1, 2008 and Dec 31, 2019 in Taiwan. Patients undergoing major elective surgery were categorised into three groups according to the type of anaesthesia administered: noninhalation anaesthesia, inhalation anaesthesia, and regional anaesthesia, matched at a 1:1 ratio. The incidence rate (IR) of dementia was determined. Findings: PSM yielded 63,750 patients (21,250 in the noninhalation anaesthesia group, 21,250 in the inhalation anaesthesia group, and 21,250 in the regional anaesthesia group). In the multivariate Cox regression analysis, the adjusted hazard ratios (aHRs; 95% confidence intervals) of dementia for the inhalation and noninhalation anaesthesia groups compared with the regional anaesthesia group were 20.16 (15.40–26.35; p

During whole genomic duplication (WGD) events, micro RNAs (miRNAs) are involved in stabilization of chromatin and genome and epigenetic regulation of gene expression. In this study, a newly induced triploid group of hybrids between sect. Tacamahaca and sect. Aigeiros in Populus, was characterized for genome-wide miRNA expression after WGD. Seven miRNA libraries (male parent, female parent, group of triploid offspring’s, group of diploid offspring, and three triploid individuals) were constructed and variation of miRNA expression from diploid parents to triploid offspring’s as well as distinction between triploid and diploid offspring were analyzed. The results showed that a total of 240 miRNAs were predicted including 187 known miRNAs and 53 novel miRNAs. 81.25% of miRNAs in triploid offspring were non-additively expressed in which 52.31% were down-regulated. A novel miRNA with 24nt in length choosing adenine as its first base was found in triploid offspring group suggesting its potential role in regulation of DNA methylation after WGD. A total of 18 novel miRNAs were specifically expressed in the library of triploid group. Targeted genes of different expressed miRNAs in three comparison sets (triploid offspring group vs female parent, male parent, and diploid offspring group) were all enriched in ADP binding (GO: 0043531; FDR < 0.05). KEGG enrichment pathway of all three comparison sets was plant-pathogen interaction. This study revealed an essential role of miRNAs involving in epigenetic regulation after WGD in poplar and provided a good model for further studies of polyploidization advantages in woody plant.

Abstract Background FLVCR1-AS1 is a key regulator of cancer progression. However, the biological functions and underlying molecular mechanisms of pancreatic cancer (PC) remain unknown. Methods FLVCR1-AS1 expression levels in 77 PC tissues and matched non-tumor tissues were analyzed by qRT-PCR. Moreover, the role of FLVCR1-AS1 in PC cell proliferation, cell cycle, and migration was verified via functional in vitro and in vivo experiments. Further, the potential competitive endogenous RNA (ceRNA) network between FLVCR1-AS1 and KLF10, as well as FLVCR1-AS1 transcription levels, were investigated. Results FLVCR1-AS1 expression was low in both PC tissues and PC cell lines, and FLVCR1-AS1 downregulation was associated with a worse prognosis in patients with PC. Functional experiments demonstrated that FLVCR1-AS1 overexpression significantly suppressed PC cell proliferation, cell cycle, and migration both in vitro and in vivo. Mechanistic investigations revealed that FLVCR1-AS1 acts as a ceRNA to sequester miR-513c-5p or miR-514b-5p from the sponging KLF10 mRNA, thereby relieving their suppressive effects on KLF10 expression. Additionally, FLVCR1-AS1 was shown to be a direct transcriptional target of KLF10. Conclusions Our research suggests that FLVCR1-AS1 plays a tumor-suppressive role in PC by inhibiting proliferation, cell cycle, and migration through a positive feedback loop with KLF10, thereby providing a novel therapeutic strategy for PC treatment.

Background: Ferroptosis is a newly proposed concept of programmed cell death and has been widely studied in many diseases during the past decade. However, a bibliometric study that concentrates on publication outputs and research trends of ferroptosis related to the brain is lacking.Methods: We retrieved publication data in the field of ferroptosis in the brain from the Web of Science Core Collection on 31 December 2021. A bibliometric analysis was performed using VOSviewer and CiteSpace software.Results: Six hundred fifty-six documents focusing on ferroptosis in the brain were published from 2012 to 2021. The number of publications in this field has shown a steady increase in recent years. Most publications were from China (338) and the United States (166), while the most productive organizations were at the University of Melbourne (34) and University of Pittsburgh (23). Ashley I. Bush was the most productive author, while Scott J Dixon was the most co-cited author. The journal Free Radical Biology and Medicine published the most articles in this field, while Cell was the most cited journal. Among 656 publications, top 10 cited documents were cited at least 300 times. Among the top 20 references with the strongest citation bursts, half of the papers had a burst until 2021. The keywords analysis suggests that the top 20 keywords appeared at least 40 times. Additionally, “amyloid precursor protein” was the keyword with strongest bursts.Conclusion: Research on ferroptosis in the brain will continue to be highly regarded. This study analyzed the research landscape of ferroptosis in the brain and offers a new reference for researchers in this field.

Developmental neurons received with sevoflurane, the commonly used inhalational anesthetic agent in clinical surgery, several times tend to be destroyed. Microglia, the resident immune cells of the central nervous system (CNS), are activated after sevoflurane exposure, accompanied by releasing proinflammatory cytokines that damage developing neurons. The sevoflurane-induced neurotoxicity could be attributed to activated microglia presenting proinflammatory and anti-inflammatory functions. Proinflammatory microglia release cytokines to impair the CNS, while anti-inflammatory microglia engulf damaged neurons to maintain CNS homeostasis. Sevoflurane exposure promotes the secretion of proinflammatory cytokines by microglia, inhibiting the microglial phagocytic function. Microglia with poor phagocytic function cannot engulf damaged neurons, leading to the accumulation of damaged neurons. The mechanism underlying poor phagocytic function may be attributed to mitochondrial dysfunction of microglia induced by sevoflurane exposure, in which affected mitochondria cannot generate adequate ATP and NAD to satisfy the energy demand. We discovered that sevoflurane treatment impaired the mitochondrial metabolism of microglia, which resulted in NAD deficiency and couldn’t produce sufficient energy to clear damaged neurons to maintain CNS development. Our findings provide an explanation of a new mechanism underlying sevoflurane-induced neurotoxicity.

BackgroundIn neonatal mice, anesthesia with sevoflurane depolarizes the GABA Type A receptor (GABAAR), which leads to cognitive impairment. Calcium accumulation in neurons can lead to neurotoxicity. Voltage-gated calcium channels (VGCCs) can increase intracellular calcium concentration under isoflurane and hypoxic conditions. The underlying mechanisms remain largely unknown.MethodsSix-day-old mice were anesthetized with 3% sevoflurane for 2 h/day for 3 days. The Y-Maze, new object recognition (NOR) test, the Barnes maze test, immunoassay, immunoblotting, the TUNEL test, and Golgi–Cox staining were used to assess cognition, calcium concentration, inflammatory response, GABAAR activation, VGCC expression, apoptosis, and proliferation of hippocampal nerve cells in mice and HT22 cells.ResultsCompared with the control group, mice in the sevoflurane group had impaired cognitive function. In the sevoflurane group, the expression of Gabrb3 and Cav1.2 in the hippocampal neurons increased (p < 0.01), the concentration of calcium ions increased (p < 0.01), inflammatory reaction and apoptosis of neurons increased (p < 0.01), the proliferation of neurons in the DG area decreased (p < 0.01), and dendritic spine density decreased (p < 0.05). However, the inhibition of Gabrb3 and Cav1.2 alleviated cognitive impairment and reduced neurotoxicity.ConclusionsSevoflurane activates VGCCs by inducing GABAAR depolarization, resulting in cognitive impairment. Activated VGCCs cause an increase in intracellular calcium concentration and an inflammatory response, resulting in neurotoxicity and cognitive impairment.

BackgroundThe neuroprotective effect of remote ischemic preconditioning (RIPC) in patients undergoing elective cardiopulmonary bypass (CPB)-assisted coronary artery bypass graft (CABG) or valvular cardiac surgery remains unclear.MethodsA randomized, double-blind, placebo-controlled superior clinical trial was conducted in patients undergoing elective on-pump coronary artery bypass surgery or valve surgery. Before anesthesia induction, patients were randomly assigned to RIPC (three 5-min cycles of inflation and deflation of blood pressure cuff on the upper limb) or the control group. The primary endpoint was the changes in S-100 calcium-binding protein β (S100-β) levels at 6 h postoperatively. Secondary endpoints included changes in Neuron-specific enolase (NSE), Mini-mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA) levels.ResultsA total of 120 patients [mean age, 48.7 years; 36 women (34.3%)] were randomized at three cardiac surgery centers in China. One hundred and five patients were included in the modified intent-to-treat analysis (52 in the RIPC group and 53 in the control group). The primary result demonstrated that at 6 h after surgery, S100-β levels were lower in the RIPC group than in the control group (50.75; 95% confidence interval, 67.08 to 64.40 pg/ml vs. 70.48; 95% CI, 56.84 to 84.10 pg/ml, P = 0.036). Compared to the control group, the concentrations of S100-β at 24 h and 72 h and the concentration of NSE at 6 h, 24 h, and 72 h postoperatively were significantly lower in the RIPC group. However, neither the MMSE nor the MoCA revealed significant between-group differences in postoperative cognitive performance at 7 days, 3 months, and 6 months after surgery.ConclusionIn patients undergoing CPB-assisted cardiac surgery, RIPC attenuated brain damage as indicated with the decreased release of brain damage biomarker S100-β and NSE.Clinical trial registration[ClinicalTrials.gov], identifier [NCT01231789].

Invalid action masking is a practical technique in deep reinforcement learning to prevent agents from taking invalid actions. Existing approaches rely on action masking during policy training and utilization. This study focuses on developing reinforcement learning algorithms that incorporate action masking during training but can be used without action masking during policy execution. The study begins by conducting a theoretical analysis to elucidate the distinction between naive policy gradient and invalid action policy gradient. Based on this analysis, we demonstrate that the naive policy gradient is a valid gradient and is equivalent to the proposed composite objective algorithm, which optimizes both the masked policy and the original policy in parallel. Moreover, we propose an off-policy algorithm for invalid action masking that employs the masked policy for sampling while optimizing the original policy. To compare the effectiveness of these algorithms, experiments are conducted using a simplified real-time strategy (RTS) game simulator called Gym-μRTS. Based on empirical findings, we recommend utilizing the off-policy algorithm for addressing most tasks while employing the composite objective algorithm for handling more complex tasks.

Abstract APOL1 encodes a secreted high-density lipoprotein, which has been considered as an aberrantly expressed gene in multiple cancers. Nevertheless, the role of APOL1 in the regulatory mechanisms of pancreatic cancer remains unknown and should be explored. We identified APOL1 was abnormally elevated in human pancreatic cancer tissues compared with that in adjacent tissues and was associated with poor prognosis. The effects of APOL1 in PC cell proliferation, cell cycle, and apoptosis was verified via functional in vitro and in vivo experiments. The results showed that knockdown of APOL1 significantly inhibited the proliferation and promoted apoptosis of pancreatic cancer. In addition, we identified APOL1 could be a regulator of NOTCH1 signaling pathway using bioinformatics tools, qRT-PCR, dual-luciferase reporter assay, and western blotting. In summary, APOL1 could function as an oncogene to promote proliferation and inhibit apoptosis through activating NOTCH1 signaling pathway expression in pancreatic cancer; therefore, it may act as a novel therapeutic target for pancreatic cancer.

Early diagnosis of cancer is crucial to initiate prompt treatment for better patient outcomes. The host immune function and its associated modulators are considered to be potential biomarkers for early cancer diagnosis. Immune and immune-checkpoint biomarkers have been reported to contribute to cancer development, while a high neutrophil-to-lymphocyte ratio has been shown to be associated with poor survival outcomes in a variety of cancers. One hundred sixty-one cancer patients were recruited to take a cost-effective novel Leukocyte ImmuneTest (LIT). LIT was measured to objectively determine the pre-treatment immune status of patients. The correlation between LIT and other conventional diagnostic markers or tumor-related variables was then investigated. Significant correlations between LIT and white blood cell count, smoking status, and tumor stage 4 were found. In addition, the LIT score significantly differentiated between malignant and benign tumors in this study population. Our work raises the possibility to use LIT for general screening surveillance before further costly specialized equipment is applied for cancer diagnosis.

BackgroundHigh flow nasal cannula is gaining increasingly used in patients undergoing endoscopic procedures. We undertook this systematic review and meta-analysis to determine whether high flow nasal cannula (HFNC) could effectively minimize the risk of hypoxemia as compared with conventional oxygen therapy (COT).MethodsWe performed a comprehensive search of Pubmed, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Web of Science. Studies involving the application of HFNC during endoscopic procedures were identified.ResultsWe included 15 randomized controlled trials (7 bronchoscopy, 8 gastrointestinal endoscopy). Patients receiving HFNC during endoscopic procedures had a significantly lower risk of hypoxemia (defined as SpO2

Introduction During the COVID-19 pandemic, approximately 10%–35% of COVID-19 infected patients experience post-COVID sequela. Among these sequelae, pain symptoms should not be neglected. In addition, the sequelae of COVID-19 also decrease the quality of life of these populations. However, meta-analyses that systematically evaluated post-COVID pain are sparse.Methods and analysis A comprehensive screening will be performed by searching MEDLINE and Embase without language restriction from inception to August 2021. Cohort studies, case–control studies, cross-sectional studies and case series will be included. Case report and interventional studies will be excluded. Studies with less than 20 participants will be also excluded. We aim to investigate the prevalence of pain-related symptoms in patients after the acute phase of COVID-19. The impact of COVID-19 on the quality of life and pain symptoms among these populations in the post-acute phase will also be evaluated. ROBINS-I tool will be used to assess the risk of bias of cohort studies. The risk of bias tool developed by Hoy et al will be used to assess the risk of bias of prevalence studies. Metaprop command in Stata will be used to estimate the pooled prevalence of pain symptoms. DerSimonian and Laird random-effects models will be used to calculate the pooled relative risks. All analyses will be calculated using Stata software (V.15.0; StataCorp)Ethics and dissemination Ethics approval is not required. Results of our study will be submitted to a peer-review journal.PROSPERO registration number CRD42021272800.

Abstract The rapid growth of the number of surgical cases in the world has brought opportunities and challenges to the development of anaesthesia. Modern anaesthesia technology provides safe and effective anaesthesia for hundreds of millions of surgical procedures each year, but there is a lot of concern about the complications (mainly cognitive dysfunction) that occur after anaesthesia exposure. Preclinical studies have demonstrated cognitive dysfunction and behavioural abnormalities that persist into adulthood after exposure to anaesthesia in rodents, revealing the potential neurotoxicity of anaesthetic drugs. In a further study, Sprague–Dawley rats treated with sevoflurane in the first week of life were then subjected to behavioural tests, and female rats were significantly more negatively affected in spatial learning than male rats, suggesting that there may be gender differences in neurotoxicity of the anaesthetic, but the specific mechanisms are unclear. According to the available data, the main hypothesis that can explain the sex difference in the effect of anaesthesia on the central nervous system development remains the difference in hormone levels between males and females. Therefore, this review briefly describes the role of neuroactive steroids in the mechanism of sex differences in neurotoxicity during the development of general anaesthetics.

Purpose There are conflicting results as to the effect of inhaled nitric oxide (iNO) therapy on the risk of acute kidney injury (AKI). The aim of this study was to perform a meta-analysis to assess the updated data. Methods We systematically searched Web of Science, the Cochrane Library, Wanfang, and PubMed for relevant randomized control trials between database inception and 9/07/2020. Relative risks (RRs) with 95% confidence intervals (CIs) predicting the risk of AKI were extracted to obtain summary estimates using fixed-effects models. The Trim and Fill method was used to evaluate the sensitivity of the results and adjust for publication bias in meta-analysis. Results 15 randomized controlled studies from 14 articles involving 1853 patients were included in the study. Analyzing the eligible studies we found: (1) iNO therapy significantly increased the risk of AKI in acute respiratory distress syndrome patients (RR 1.55, 95% CI 1.15–2.10, p = 0.004; I2 for heterogeneity 0%; Phet = 0.649). (2) The use of iNO was associated with reduced AKI risk in patients undergoing cardiac surgery (RR 0.80, 95% CI 0.64–0.99, p = 0.037; I2 for heterogeneity 0%; Phet = 0.528). (3) For organ transplantation recipients, there was no effect of iNO administration on the risk of AKI (RR 0.50, 95% CI 0.16–1.56, p = 0.233; I2 for heterogeneity 0%; Phet = 0.842). The Trim and Fill analysis showed that the overall effect of this meta-analysis was stable. Conclusions The effect of iNO on AKI risk might be disease-specific. Future RCTs with larger patient populations should aim to validate our findings.

Purpose: To use pathologic indicators to determine which patients benefit from postmastectomy radiation therapy (PMRT) for breast cancer after neoadjuvant chemotherapy (NACT) and total mastectomy (TM). Patients and methods: We enrolled 4236 patients with breast invasive ductal carcinoma who received NACT followed by TM. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals; independent predictors were controlled for or stratified in the analysis. Results: After multivariate Cox regression analyses, the adjusted HRs derived for PMRT for all-cause mortality were 0.65 (0.52–0.81, P

Purpose: To investigate the outcomes of adjuvant whole breast radiation therapy (WBRT) in patients with invasive ductal carcinoma of the breast (breast IDC) receiving preoperative systemic therapy (PST) and breast-conserving surgery (BCS), and their prognostic factors, considering overall survival (OS), locoregional recurrence (LRR), distant metastasis (DM), and disease-free survival. Patients and methods: Patients diagnosed as having breast IDC and receiving PST followed by BCS were recruited and categorized by treatment into non-breast radiation therapy [BRT] (control) and WBRT (case) groups, respectively. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs). Results: Multivariate Cox regression analyses indicated that non-BRT, cN3, and pathologic residual tumor (ypT2–4) or nodal (ypN2–3) stages were poor prognostic factors for OS. The adjusted HRs (aHRs; 95% CIs) of the WBRT group to non-BRT group for all-cause mortality were 0.14 (0.03–0.81), 0.32 (0.16–0.64), 0.43 (0.23–0.79), 0.23 (0.13–0.42), 0.52 (0.20–1.33), and 0.34 (0.13–0.87) in the ypT0, ypT1, ypT2–4, ypN0, ypN1, and ypN2–3 stages, respectively. The aHRs (95% CIs) of the WBRT group to non-BRT group for all-cause mortality were 0.09 (0.00–4.07), 0.46 (0.26–0.83), 0.18 (0.06–0.51), 0.28 (0.06–1.34), 0.25 (0.10–0.63), 0.47 (0.23–0.88), and 0.32 in the cT0–1, cT2, cT3, cT4, cN0, cN1, and cN2–3 stages, respectively. The WBRT group exhibited significantly better LRR-free and DM-free survival than the non-BRT group, regardless of the clinical T or N stage or pathologic response after PST. Conclusion: WBRT might lead to superior OS and LRR-free and DM-free survival compared with the non-BRT group, regardless of the initial clinical TN stage or pathologic response.

Oligodendrocytes (OLs) participate in the formation of myelin, promoting the propagation of action potentials, and disruption of their proliferation and differentiation leads to central nervous system (CNS) damage. As surgical techniques have advanced, there is an increasing number of children who undergo multiple procedures early in life, and recent experiments have demonstrated effects on brain development after a single or multiple anesthetics. An increasing number of clinical studies showing the effects of anesthetic drugs on the development of the nervous system may mainly reside in the connections between neurons, where myelin development will receive more research attention. In this article, we review the relationship between anesthesia exposure and the brain and OLs, provide new insights into the development of the relationship between anesthesia exposure and OLs, and provide a theoretical basis for clinical prevention of neurodevelopmental risks of general anesthesia drugs.

BackgroundDexmedetomidine (DEX) administration decreases post-operative nausea and vomiting (PONV), but it is a lack of large-scale retrospective cohort study and is unclear whether there is a dose-relationship and optimal dose for antiemetic effects between DEX and PONV. We performed a large-scale retrospective cohort study to explore the optimal dose of intraoperative DEX for antiemetic effects of PONV.MethodsA total of 5,310 patients aged ≥18 who underwent elective thoracic surgery from January 2016 to March 2020 under total intravenous anesthesia (TIVA) or combined intravenous and inhalation anesthesia in Henan Provincial People's Hospital. Patients were divided into two groups, those who received DEX intraoperatively and those who did not receive DEX. Patients who received DEX after surgery were excluded. Our primary outcomes were the association, the dose-response relationship, and the optimal dose for antiemetic effects between intraoperative DEX and PONV.ResultsAmong the 3,878 patients enrolled, 2,553 patients received DEX and 1,325 patients did not receive DEX. The incidence of PONV in patients who received DEX was 21.3%, and the incidence of PONV in patients who did not receive DEX was 46.5% (P = 0.001). After the matched-pairs cohort consisted of 1,325 patients, the incidence of PONV in patients who received DEX was 23.6%, and the incidence of PONV in patients who did not receive DEX was 46.5% (P = 0.001). We analyzed three different models after propensity matching to validate the stability of the prediction model between intraoperative DEX and PONV. A dose-response relationship between intraoperative DEX and PONV was observed. The optimal dose range of intraoperative DEX for antiemetic effects of PONV is 50–100 μg in elective thoracic surgery.ConclusionsIntraoperative DEX was associated with a decreased incidence of PONV in the large-scale retrospective cohort study. A dose-response relationship between intraoperative DEX and PONV was observed. The optimal dose range of intraoperative DEX for antiemetic effects of PONV is 50–100 μg in elective thoracic surgery.

PurposeWe examined locoregional recurrence (LRR) in patients with breast invasive ductal carcinoma (IDC) receiving total mastectomy (TM) under propofol-based paravertebral block-regional anesthesia (PB-RA) versus sevoflurane-based inhalational general anesthesia (INHA-GA) without propofol. All-cause death and distant metastasis were secondary endpoints.Patients and MethodsPatients with breast IDC receiving TM were recruited through propensity score matching and categorized into INHA-GA with sevoflurane and PB-RA with propofol groups. Cox regression analysis was performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsIn the multivariate Cox regression analysis, the adjusted HR (aHR; 95% CI) of LRR for the PB-RA with propofol group was 0.52 (0.28–0.96) compared with the INHA-GA with sevoflurane group. The aHRs of LRR for differentiation grade II, grade III, the American Joint Committee on Cancer clinical stage II, stage III, pathological tumor (pT) stage 2, pT stage 3–4, pathological nodal (pN) stage 1, and pN stage 2–3 were 1.16 (1.04–2.08), 1.28 (1.07–2.12), 3.71 (1.82–7.59), 4.67 (1.65–13.18), 1.09 (1.02–1.21), 1.17 (1.03–2.16), 1.10 (1.03–1.33), and 1.22 (1.06–2.41), respectively, compared with differentiation grade I, clinical stage I, pT1, and pN0. The aHR of LRR for adjuvant RT was 0.88 (0.64–0.94) compared with that for no adjuvant RT.ConclusionPB-RA with propofol might be beneficial for reducing LRR in women with breast IDC receiving TM compared with INHA-GA without propofol.

ImportancePostoperative nausea and vomiting (PONV) gives patients a bad experience and negates their good recovery from surgery.ObjectiveThis trial aims to assess the preventive effectiveness of transcutaneous electrical acupoint stimulation (TEAS) on the incidence of PONV in high-risk surgical patients.DesignThe large sample size, multicenter, evaluator-blinded, and randomized controlled study was conducted between September 3, 2019 to February 6, 2021.SettingThe 12 hospitals were from different Chinese provinces.ParticipantsAfter obtaining ethics approval and written informed consent, 1,655 patients with Apfel score ≥ 3 points were enrolled for selective laparoscopic non-gastrointestinal surgery under general anesthesia.InterventionsPatients were randomly allocated into the TEAS and Sham group with a 1:1 ratio. The TEAS group was stimulated on bilateral Neiguan and Zusanli acupoints after recovery from anesthesia on the surgical day and the next morning for 30 min, while the Sham group received an identical setting as TEAS but without currents delivered. Electronic patient self-reported scale was used to evaluate and record the occurrence of PONV.Main Outcomes and MeasuresPrimary clinical end point is the incidence of PONV which was defined as at least one incidence of nausea, retching, or vomiting after operation within postoperative 24 h.ResultsCompared with the Sham treatment, the TEAS lowered the PONV incidence by 4.8% (29.4 vs. 34.2%, P = 0.036) and vomiting incidence by 7.4% (10.4 vs. 17.8%, P < 0.001). TEAS also lowered persistent nausea incidence and PONV scores and decreased PONV related complications and Quality of Recovery−40 scores (P < 0.05). TEAS lowered the 24 h PONV risk by 20% (OR, 0.80, 95% CI, 0.65 −0.98; P = 0.032), and lowered hazard ratio by 17% (HR, 0.83, 95% CI, 0.70–0.99; P = 0.035). Both TEAS and palonosetron were the independent PONV risk protective factors for 24 h PONV incidence and cumulative PONV incidence. The combination of TEAS and palonosetron was the most effective strategy to reduce the PONV incidence (P < 0.001).Conclusions and RelevanceTEAS attenuated the PONV incidence and severity in high-risk surgical patients and may be applied clinically as a complement therapy to prevent PONV.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT04043247, identifier: NCT04043247.

BackgroundAssessing the phenotypic diversity underlying tumor progression requires the identification of variations in the respective molecular interaction in the tumor microenvironment (TME). Despite emerging studies focusing on the association between cation-chloride cotransporters (CCCs) and carcinogenesis, direct evidence that CCCs (KCC2 and NKCC1) mediate tumor progression in pan-cancer remains unclear.MethodsWe conducted a comprehensive assessment of the expression, DNA variation profiles, and prognostic and immunologic implications of CCCs based on a large-scale pan-cancer population, including 10,967 cancer patients from the Cancer Genome Atlas, 9,162 cancer patients from Genomics Expression Omnibus, 48,834 cancer patients from 188 independent studies, and 356 cancer patients from three real-world cohorts.ResultsIn this study, we first found that CCCs were highly expressed in most tumors, and prominently associated with prognosis. Kaplan–Meier analysis and Cox regression analysis revealed that KCC2 and NKCC1 significantly predicted survival for patients with pan-cancer, suggesting that CCCs have inconsistent tumorigenesis regulatory mechanisms in cancers. Next, we examined the DNA variation landscape of KCC2 and NKCC1 and their prognostic implications in pan-cancer. The results demonstrated that UCEC patients with somatic copy number variation (CNV) of NKCC1 received significantly better outcomes (p < 0.05). Besides emphasizing the clinical implications of CNV of CCCs for cancer patients, we found that NKCC1MUT could prominently prolong progression-free survival (p = 2.59e-04), disease-specific survival (p = 0.019), and overall survival (p = 0.034) compared with NKCC1WT cancer patients possibly via regulation of cell proliferation and oncogenic stress pathways. Additionally, KCC2 positively correlated with the levels of tumor-infiltrating macrophages and CD4+ T cells, but NKCC1 showed a significantly widely negative association with tumor-infiltrated lymphocytes, suggesting an immune-excluded TME in cancers. Similarly, expression of KCC2, rather than NKCC1, was positively correlated with the immune checkpoint molecules, indicating its role as an immune regulator in a wide variety of cancers. Finally, to verify our hypothesis and altered expression of CCCs, we performed IHC analysis and revealed the staining distribution in tumor and adjacent normal tissues of glioma, clear cell renal cell carcinoma, papillary cell renal cell carcinoma, and hepatocellular and breast cancer from three real-world cohorts, and validated prominently prognostic implications of CCCs in patients with clear cell renal cell carcinoma.ConclusionThis study first comprehensively investigated the molecular and clinical role of CCCs, and illustrated the significant association among KCC2/NKCC1 expression, DNA variation profiles prognosis, and TME of pan-cancer. The pan-cancer findings provided an in-depth understanding of potential oncogenic and immunologic of differential expression and DNA alteration of KCC2/NKCC1 cancers.