General anesthetic action profile on the human prefrontal cortex cells through comprehensive single-cell RNA-seq analysis.

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 (<2 h) altered transcriptome profiling across microglia, excitatory neurons, interneurons, astrocytes and oligodendrocyte progenitor cells. Utilizing scRNA-seq as a robust and high-through put tool, our work may provide a comprehensive blueprint for future mechanistic studies of general anesthetics in clinically relevant settings.

The efficacy of "TiRobot"orthopaedic robot-assisted VS conventional fluoroscopic percutaneous screw fixation of the sacroiliac joint.

PURPOSE: This study is to compare the precision and safety of the orthopaedic robot with conventional fluoroscopy for assisted percutaneous sacroiliac joint screw implantation. METHODS: Retrospective analysis was performed on the clinical data of 57 patients with unstable posterior pelvic ring injuries who were admitted and met the criteria between January 2017 and January 2022. All of these patients underwent percutaneous sacroiliac joint screw implantation, and their clinical data were split into two groups based on the surgical technique: a RA group (robot-assisted implantation, 30 patients, 54 screws) and a CF group (conventional fluoroscopic freehand implantation, 27 patients, 42 screws). There were 96 screws placed in total. The durations of the two groups' operations, fluoroscopy examinations, fluoroscopy doses, total number of fluoroscopies, and intra-operative guide pin applications were noted and compared. On post-operative CT scans, the placement of each screw was assessed using the Gertzbein-Robbins classification. Finally, imaging Matta criteria were used to assess the sacroiliac joint fracture reduction. The Majeed functional score was used to assess clinical function. RESULTS: Both groups successfully completed 57 procedures in total. In both groups, there were no consequences from vascular injury, wound infection, or urinary tract infection. Additionally, there were no complications from robotic-induced nerve injury, operating time, fluoroscopic dose, and the frequency of fluoroscopic; the number of percutaneous punctures in the RA group was lower than that of the CF group.There were statistically significant differences between the aforementioned data (P < 0.05). The modified Matta evaluated the effectiveness of fracture reduction. In the RA group, there was no statistically significant difference between the CF group (P > 0.05). According to the modified Gertzbein-Robbins classification criteria, the 54 screws implanted in the RA group were classified as follows: class A (45), class B (5), class C (4), and class D (0); the accuracy rate of the implants was 92.59%. Forty-two screws implanted in the CF group, 30 screws were defined class A, class B (3), class C (7), and class D (2). The accuracy rate of the implants was 78.57%(χ2 = 3.967, P < 0.05). There was a statistically significant difference between the two groups. The Majeed score 30 patients in RA group, one month post-operation, 16 considered exceptional, eight decent, six moderate, and zero bad. Post-operation more than six months,25 recorded exceptional, five decent. By the time,27 patients in CF group,12 exceptional grade, eight decent, six moderate, and one bad,one month post-operation. Post-operation more than six months,22 recorded exceptional, five decent.Both group (P > 0.05). CONCLUSION: "TiRobot" robot-assisted screw implant treatment for unstable posterior pelvic ring injury has a greater success rate than traditional surgery as compared to conventional percutaneous screw implant. It is a precise, secure, and minimally invasive surgical technique that can also be applied to severe pelvic injuries even congenital sacral deformities.

Dexmedetomidine Diminishes, but Does Not Prevent, Developmental Effects of Sevoflurane in Neonatal Rats.

BACKGROUND: Sevoflurane (SEVO) increases neuronal excitation in neonatal rodent brains through alteration of gamma aminobutyric acid (GABA)(A) receptor signaling and increases corticosterone release. These actions may contribute to mechanisms that initiate the anesthetic's long-term neuroendocrine and neurobehavioral effects. Dexmedetomidine (DEX), a non-GABAergic α2-adrenergic receptor agonist, is likely to counteract SEVO-induced neuronal excitation. We investigated how DEX pretreatment may alter the neurodevelopmental effects induced by SEVO in neonatal rats. METHODS: Postnatal day (P) 5 Sprague-Dawley male rats received DEX (25 µg/kg, intraperitoneal) or vehicle before exposure to 2.1% SEVO for 6 hours (the DEX + SEVO and SEVO groups, respectively). Rats in the DEX-only group received DEX without exposure to SEVO. A subcohort of P5 rats was used for electroencephalographic and serum corticosterone measurements. The remaining rats were sequentially evaluated in the elevated plus maze on P80, prepulse inhibition of the acoustic startle response on P90, Morris water maze (MWM) starting on P100, and for corticosterone responses to physical restraint for 30 minutes on P120, followed by assessment of epigenomic DNA methylation patterns in the hippocampus. RESULTS: Acutely, DEX depressed SEVO-induced electroencephalogram-detectable seizure-like activity (mean ± SEM, SEVO versus DEX + SEVO, 33.1 ± 5.3 vs 3.9 ± 5.3 seconds, P < .001), but it exacerbated corticosterone release (SEVO versus DEX + SEVO, 169.935 ± 20.995 versus 280.853 ± 40.963 ng/mL, P = .043). DEX diminished, but did not fully abolish, SEVO-induced corticosterone responses to restraint (control: 11625.230 ± 877.513, SEVO: 19363.555 ± 751.325, DEX + SEVO: 15012.216 ± 901.706, DEX-only: 12497.051 ± 999.816; F[3,31] = 16.878, P < .001) and behavioral deficiencies (time spent in the target quadrant of the MWM: control: 31.283% ± 1.722%, SEVO: 21.888% ± 2.187%, DEX + SEVO: 28.617% ± 1.501%, DEX-only: 31.339% ± 3.087%; F[3,67] = 3.944, P = .012) in adulthood. Of the 391 differentially methylated genes in the SEVO group, 303 genes in the DEX + SEVO group had DNA methylation patterns that were not different from those in the control group (ie, they were normal). DEX alone did not cause acute or long-term functional abnormalities. CONCLUSIONS: This study suggests that the ability of DEX to depress SEVO-induced neuronal excitation, despite increasing corticosterone release, is sufficient to weaken mechanisms leading to long-term neuroendocrine/neurobehavioral abnormalities. DEX may prevent changes in DNA methylation in the majority of genes affected by SEVO, epigenetic modifications that could predict abnormalities in a wide range of functions.

An atlas of dynamic peripheral blood mononuclear cell landscapes in human perioperative anaesthesia/surgery.

BACKGROUND: The number of patients receiving anaesthesia is increasing, but the impact of general anaesthesia on the patient's immune system remains unclear. The aim of the present study is to investigate dynamics of systemic immune cell responses to anaesthesia during perioperative period at a single-cell solution. METHODS: The peripheral blood mononuclear cells (PBMCs) and clinical phenomes were harvested and recorded 1 day before anaesthesia and operation, just after anaesthesia (0 h), and 24 and 48 h after anaesthesia. Single-cell sequencing of PBMCs was performed with 10× genomics. Subsequently, data analysis was performed with R packages: Seurat, clusterProfiler and CellPhoneDB. RESULTS: We found that the cluster of CD56+ NK cells changed at 0 h and the cluster of monocytes increased at 24 and 48 h after anaesthesia. The characteristic genes of CD56+ NK cells were mainly enriched in the Jak-STAT signalling pathway and in cell adhesion molecules (24 h) and carbon metabolism (48 h). The communication between CD14+ monocytes and other cells decreased substantially 0 and 48 h after operation. The number of plasma cells enriched in protein export in men was substantially higher than that in women, although the total number in patients decreased 24 h after operation. CD14+ monocytes dominated that cell-cell communications appeared in females, while CD8+ NKT cells dominated that cell-cell communications appeared in male. The number of plasma cells increased substantially in patients with major surgical trauma, with enrichments of pentose phosphate pathway. The communications between plasma cells with other cells varied between surgical severities and anaesthetic forms. The intravenous anaesthesia caused major alterations of cell types, including CD14+ monocytes, plasmas cells and MAIT cells, as compared with inhalation anaesthesia. CONCLUSION: We initially reported the roles of perioperative anaesthesia/surgery in temporal phenomes of circulating immune cells at a single-cell solution. Thus, the protection against immune cell changes would benefit the recovery from anaesthesia/surgery.

Contemporary external beam radiotherapy boost or high dose-rate brachytherapy boost for cervical cancer: a propensity-score-matched, nationwide, population-based cohort study.

To estimate the survival effects of contemporary external beam radiotherapy (EBRT) boost modalities (intensity-modulated radiation therapy or volumetric modulated arc therapy) and high dose-rate brachytherapy (HDR-BT) boost in patients with cervical cancer (CC). Patients who had been diagnosed as having CC were recruited from the Taiwan Cancer Registry Database. Propensity score matching was performed, and Cox proportional-hazards model curves were used to analyze the all-cause mortality of patients who received standard whole-pelvis irradiation with different boost modalities. The matching process yielded a final cohort of 1,630 patients (815 in the EBRT boost and HDR-BT boost groups, respectively) eligible for further analysis. The multivariate Cox regression analyses indicated that the adjusted hazard ratio (95% confidence intervals) for EBRT boost compared with HDR-BT boost was 1.62 (1.43-1.84). Multivariable analysis revealed that the independent poor prognostic factors of all-cause mortality among patients with CC were adenocarcinoma, no chemotherapy, Charlson comorbidity index score ≥ 1, age ≥ 60 years, and advanced International Federation of Gynecology and Obstetrics stage. HDR-BT boost may be more beneficial than contemporary EBRT boost in selected patients with CC.

Factors affecting the risk of SARS-CoV-2 transmission to anesthesiologists performing endotracheal intubation in patients with SARS-CoV-2.

BACKGROUND: In this study, we estimated the predictive factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in anesthesiologists performing endotracheal intubation in patients with confirmed SARS-CoV-2. METHOD: We analyzed data from a survey conducted by the Chinese Society of Anesthesiology Task Force on Airway Management on endotracheal intubation in 98 patients with SARS-CoV-2 confirmed through nucleic acid testing and chest computed tomography. The multivariate logistic model with stepwise selection was used for selecting the predictive factors significantly associated with SARS-CoV-2 infection in the corresponding anesthesiologists. RESULTS: SARS-CoV-2 prevalence in the corresponding anesthesiologists was 20.41% after intubation in patients with SARS-CoV-2. Univariate analysis indicated that intubation for elective treatment, intubation in an operating room or isolation ward, and routine rapid induction with continuous positive-pressure ventilation (PPV) for intubation were associated with a lower SARS-CoV-2 risk in the anesthesiologists. Multivariate analysis revealed that intubation for elective treatment was associated with a significantly decreased SARS-CoV-2 risk (adjusted odds ratio [aOR] = 0.28, 95% confidence interval [CI]: 0.14-0.68, P < 0.0001), and coughing by patients during endotracheal intubation was associated with a significantly increased SARS-CoV-2 risk (aOR = 1.70, 95% CI: 1.39-2.97, P = 0.0404) in the anesthesiologists. CONCLUSION: Endotracheal intubation for elective treatments, intubation in an operating room or isolation ward, and routine rapid induction with continuous PPV for patients with confirmed SARS-CoV-2 are associated with a lower risk of SARS-CoV-2 transmission in practicing anesthesiologists, and coughing by patients during intubation increases the risk.

Roles of Testosterone and Estradiol in Mediation of Acute Neuroendocrine and Electroencephalographic Effects of Sevoflurane During the Sensitive Period in Rats.

Testosterone (T), predominantly acting through its derivative 17ß-estradiol (E2), regulates the brain's sexual differentiation in rodents during the perinatal sensitive period, which mirrors the window of vulnerability to the adverse effects of general anesthetics. The mechanisms of anesthesia's adverse effects are poorly understood. We investigated whether sevoflurane alters T and E2 levels and whether they contribute to sevoflurane's acute adverse effects in postnatal day 5 Sprague-Dawley rats. The rats underwent electroencephalography recordings for 2 h of baseline activity or for 1 h before and another hour during 2.1% sevoflurane exposure, followed by collection of trunk blood and brain tissue. Pharmacological agents, including the GABA type A receptor inhibitor bicuculline and the aromatase inhibitor formestane, were administered 30 min before sevoflurane anesthesia. Sevoflurane increased serum T levels in males only. All other effects of sevoflurane were similar in both sexes, including increases in serum levels of E2, hypothalamic mRNA levels of aromatase, estrogen receptor α (Erα) [not estrogen receptor ß (Erß)], Na+-K+-Cl- cotransporter (Nkcc1)/K+-Cl- cotransporter (Kcc2) mRNA ratio, electroencephalography-detectable seizures, and stress-like corticosterone secretion. Bicuculline and formestane alleviated these effects, except the T level increases. The ERα antagonist MPP, but not the ERß antagonist PHTPP, reduced electroencephalography-detectable seizures and normalized the Nkcc1/Kcc2 mRNA ratio. Collectively, sevoflurane exacerbates levels of T in males and E2 in both sexes during the period of their organizational effects in rodents. Sevoflurane acts through GABAAR-mediated, systemic T-independent elevation of E2 to cause electroencephalography-detectable seizures, stress-like corticosterone secretion, and changes in the expression of genes critical for brain development.

Acquired infection after intubating patients with COVID-19: Datasets.

Thirty-six anesthesia departments in 36 hospitals in four provinces of China where an outbreak of COVID-19 occurred were surveyed. We found that there were ten anesthesiologists (5 male and 5 female) who contracted the infection after performing intubation, as well as 4 nurses (1 male and 3 female) who contracted the infection after assisting with the intubation. This is a retrospective investigation and no intervention was applied. The numbers are presented as mean ± Standard Deviation (SD). We used Graphpad Prism (version 8.2.1 Windows version, GraphPad Software, San Diego). Fisher's exact test at a two-sided significance level of 0.05 was used to identify potential risk factor (s) for intubation providers. A P value less than 0.05 is considered statistically significant. A total of 211 anesthesiologists from four provinces were involved in the intubation of 664 patients with confirmed or potential COVID-19. Of these 644 patients, 640 cases were eventually confirmed with a diagnosis of COVID-19. Among the 211 anesthesiologists who performed intubation, 10 of them had a confirmed diagnosis of COVID-19 afterwards. Coughing is a risk factor for provider infection (P = 0.0001). The number of intubation attempts (within three attempts) did not increase the risk of the infection. All of the affected anesthesiologists had symptoms 2-12 days after the intubation encounter (average 6 ±â€¯3 days). All had radiological image evidence of bilateral pneumonia and all reported relatively mild symptoms. The affected doctors were out of clinical service for 20-60 days (average 46 ±â€¯12 days). Seven of the doctors have been discharged from the hospital, but three of them remain hospitalized. Four nurses who assisted with intubations contracted COVID-19. One of these nurses was in critical condition but was eventually discharged with a loss of 50 days of clinical service. The remaining three nurses have had mild symptoms so far, but one is still hospitalized.

[Kinetic migration of 4-cumylphenol and 4-tert-butylphenyl salicylate from paper packaging to dry food simulant Tenax TA].

Migration investigations were carried out on paper food packaging in contact with dry food simulant Tenax TA. The aim was to explore the migration behaviours of 4-cumylphenol (CP) and 4-tert-butylphenyl salicylate (TBS) as potential contaminants, from paper materials to Tenax TA at different migration temperatures for variant migration times. A method based on ultrahigh performance liquid chromatography coupled with fluorescence detection (UPLC-FLR) was developed to determine CP and TBS migrated into the simulant. Two independent migration tests performed under open system and closed system were contrastively studied. At the same time, a series of migration tests by using different masses of Tenax TA to contact round paper samples with the diameter of 3. 5 cm was conducted to explore the proper ratio between the mass of Tenax TA and the area of food packaging sample. Based on the analytical results, high temperature and long contact time had positive effect on the migration rate of the contaminants. However, persistent high migration temperature would lead to decrease the migration rate due to desorption of CP and TBS from Tenax TA. Migration rate in closed system was higher than that in open system. In the process of migration test, a ratio of 4. 16 g/dm2 was an appropriate experimental condition to conduct the migration test. All of the migration results revealed that the proper ratio of mass of Tenax TA to area of paper sample was the key to conduct the exposure assessment of food contact materials.

Protective effects of dexmedetomidine on blunt chest trauma-induced pulmonary contusion in rats.

BACKGROUND: Dexmedetomidine is a new and highly selective α2-adrenoreceptor agonist with potent anti-inflammatory capacity. This study explored the effects of dexmedetomidine on regulating hemodynamics, the plasma tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) levels, immunohistochemical localization of nuclear factor κB (NF-κB) from blunt chest trauma-induced pulmonary contusion in rats. METHODS: Fifty Sprague-Dawley rats were randomly assigned into five equal groups (n = 10) as follows: uninjured control group, uninjured plus dexmedetomidine group, injured group, injured plus dexmedetomidine group, injured plus dexmedetomidine plus yohimbine (IDY), an α2-adrenergic receptor antagonist, group. Dexmedetomidine was infused continuously through the left femoral vein cannula at the rate of 5.0 µg/kg per hour after blunt chest trauma 30 minutes in uninjured plus dexmedetomidine group, injured plus dexmedetomidine group, and IDY group. Animals in the IDY group received 0.2-mg/kg yohimbine immediately after the administration of dexmedetomidine. The right femoral artery was cannulated to monitor mean arterial pressure and heart rate and to draw blood samples. The plasma TNF-α and IL-1ß levels were measured using enzyme-linked immunosorbent assays. The lung tissue NF-κB expression was determined by immunohistochemistry. RESULTS: Bilateral blunt chest trauma produced progressive hypotension and a prolonged descent in heart rate. The plasma TNF-α and IL-1ß levels as well as the NF-κB activation of lung significantly increased after blunt chest trauma challenge alone. Dexmedetomidine not only significantly modified hemodynamics and relieved the infiltration of inflammatory cells into alveolar spaces but also inhibited the plasma TNF-α and IL-1ß production as well as the lung NF-κB activation (p < 0.05, respectively). Yohimbine treatment significantly reversed the effects of dexmedetomidine (p < 0.05). CONCLUSION: The administration of dexmedetomidine has beneficial effects on pulmonary contusion from blunt chest trauma in rats. The mechanisms were likely to inhibit the NF-κB activation via α2-adrenergic receptors and attenuate the proinflammatory cytokine responses.

[Determination of photoinitiators in printing inks used in food contact materials].

A new analytical method based on gas chromatography-mass spectrometry (GC-MS) techniques was developed for the determination of five photoinitiators (PIs), benzophenone (BP), 4-methylbenzophenone (MBP), ethyl-4-dimethylaminobenzoate (EDAB), 2-ethylhexyl-4-dimethylaminobenzoate (EHDAB) and 1-hydroxycyclohexyl phenyl ketone (Irgacure 184), in the printing inks used in food contact materials. The test solutions were extracted from selected food contact materials using Soxhlet extractor with ethyl acetate as the extraction solvent. By adding 50 and 200 microg/L of a standard mixture of photoinitiators into the extracts of the blank packaging materials, the recoveries obtained were in the range of 66.7%-89.4%. The repeatability of the method was assessed by determining the contents of the photoinitiators in five types of food contact materials, and the results were lower than 10%. The instrumental detection limits (IDLs) and method quantification limits (MQLs) were in the range of 2.9-6.0 microg/L and 0.0017-0.0036 mg/dm2, respectively. The method was applied in the analysis of about twenty real samples (yogurt carton, milk carton, fruit juice carton and plastic bags samples). The most significant pollutants were BP and MBP. The concentrations of Irgacure 184, EDAB and EHDAB found in three individual samples were 0.84 mg/dm2, 0.2 mg/dm2 and 1.2 mg/dm2, respectively. The work proposed a new method to analyze the migration level of initiators from the inks.

[Determination of antioxidant residues in polymer food package using gas chromatography].

A new method for the determination of antioxidants, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA) and tertiary butylhydroquinone (TBHQ) in plastic food package by gas chromatography-electron capture detection (ECD) was developed. The antioxidants were extracted by cyclohexane with ultrasonic extraction, separated by an HP-50 + chromatographic column (30 m x 0.53 mm x 1 microm) and quantified by external standard method with an ECD detector. The average recoveries of antioxidants were 88% -93%, 92% - 101% and 83% -97% for BHT, BHA and TBHQ, respectively, at the spiking levels of 3.00 - 10.0 mg/kg. The corresponding relative standard deviations (RSDs, n = 5) were 2.01% - 2.89%, 2.11% - 3.19% and 2.99% - 4.02%, respectively. The limits of detection (S/N = 3) were 0.5, 0.5 and 0.8 mg/kg for BHT, BHA and TBHQ, respectively. The proposed method has been applied to the analysis of 5 kinds of polymer food package. The results indicated that all the above antioxidants were found in the practical polymer food package samples. Plastic food package contained BHT and BHA with the concentrations varying from 6.3 to 7.8 mg/kg and rubber food package contained all the three antioxidants with the concentrations varying from 9.3 to 28.4 mg/kg. This method is accurate, sensitive, highly reproducible and suitable for the analysis of residual antioxidants in polymer food package.