First insight of the intergenerational effects of tri-n-butyl phosphate and polystyrene microplastics to Daphnia magna.

As an emerging organic pollutant, tributyl phosphate (TnBP) can be easily adsorbed by microplastics, resulting in compound toxic effects. In the present work, the effects of polystyrene microplastics (PS-MPs) and TnBP on the survival, growth, reproduction and oxidative stress of Daphnia magna (D. magna) have been evaluated through multigenerational test. Compared with the alone exposure groups, the somatic growth rate and the expression values of growth related genes rpa1, mre11, rnha, and rfc3_5 in the F1 generation of the combined exposure groups were significantly lower (p < 0.05), indicating synergistic effect of PS-MPs and TnBP on the growth toxicity and transgenerational effects. In addition, compared with the PS-MPs groups, significantly lower average number of offspring and expression values of reproduction related genes ccnb, mcm2, sgrap, and ptch1 were observed in the combined exposure group and TnBP group (p < 0.05), indicating TnBP might be the major factor causing reproductive toxicity to D. magna. Although PS-MPs and TnBP alone or in combination also had toxic impacts on the growth, survival and reproduction of D. magna in generations F0 and F2, the effects were less than F1 generation. Regarding oxidative stress, the activity of SOD, CAT and GSH-Px and MDA content in the generations F0 and F1 of combined exposure groups were higher than the TnBP group but lower than the PS-MPs groups, suggesting that PS-MPs might be the dominant cause of the oxidative damage in D. magna and the presence of TnBP would alleviate oxidative stress by reducing the bioaccumulation of PS-MPs. The present work will provide a theoretical basis for further understanding of the toxic effects and ecological risks of combined TnBP and microplastic pollution on aquatic organisms.

A microglial activation cascade across cortical regions underlies secondary mechanical hypersensitivity to amputation.

Neural mechanisms underlying amputation-related secondary pain are unclear. Using in vivo two-photon imaging, three-dimensional reconstruction, and fiber photometry recording, we show that a microglial activation cascade from the primary somatosensory cortex of forelimb (S1FL) to the primary somatosensory cortex of hindlimb (S1HL) mediates the disinhibition and subsequent hyperexcitation of glutamatergic neurons in the S1HL (S1HLGlu), which then drives secondary mechanical hypersensitivity development in ipsilateral hindpaws of mice with forepaw amputation. Forepaw amputation induces rapid S1FL microglial activation that further activates S1HL microglia via the CCL2-CCR2 signaling pathway. Increased engulfment of GABAergic presynapses by activated microglia stimulates S1HLGlu neuronal activity, ultimately leading to secondary mechanical hypersensitivity of hindpaws. It is widely believed direct neuronal projection drives interactions between distinct brain regions to prime specific behaviors. Our study reveals microglial interactions spanning different subregions of the somatosensory cortex to drive a maladaptive neuronal response underlying secondary mechanical hypersensitivity at non-injured sites.

Tourism image classification based on convolutional neural network SqueezeNet--Taking Slender West Lake as an example.

Tourism image classification plays an important role in the study of clarifying the real perception of tourism resources by tourists, which cannot be studied in depth by human vision alone. The development of convolutional neural networks in computer vision brings new opportunities for tourism image classification research. In this study, SqueezeNet, a lightweight convolutional neural network, was selected and improved on the basis of the original model for 3740 Slender West Lake tourism image datasets. It is found that the validation accuracy of the model is up to 85.75%, and the size is only 2.64 MB, which is a good classification effect. This reduces the parameters while ensuring high accuracy classification of tourism images, providing a more scientific reference for the study of tourism images and pointing out a new direction for the development and planning of tourism resources.

Chaotic signal denoising based on energy selection TQWT and adaptive SVD.

Aiming at the problem of denoising chaotic signals with low signal-to-noise ratio and unknown dynamic system parameters, a new chaotic signal denoising algorithm is proposed, which combines adjustable Q-factor wavelet transform (TQWT) and adaptive singular value decomposition (ASVD). This method uses TQWT to decompose the noisy chaotic signal. According to the maximum wavelet entropy theory and energy threshold rule, the subband of TQWT is accurately divided into signal subband and noise subband. For noise subbands, adaptive SVD is used to denoise them, to achieve preliminary denoising. In ASVD, the standard deviation of the singular value subset is used to determine the effective reconstruction order to improve the noise suppression effect. To further remove noise in the signal subband, TQWT reconstruction is performed on the preliminarily denoised signal, and ASVD is used to denoise the reconstructed signal again to obtain the chaotic signal after secondary denoising. Chua's simulated signal and four kinds of underwater radiated noise measured by TQWT-ASVD were denoised, and compared with the SVD denoising method, TQWT denoising method, complete ensemble empirical mode decomposition with adaptive noise and threshold denoising method (CEEMDAN-WT) and modified ensemble empirical mode decomposition combined with least squares denoising method (MEEMD-LMS), The experimental results show that the TQWT-ASVD method can reduce the noise of chaotic signals more effectively. Compared with SVD, TQWT, CEEMDAN-WT, MEEMD-LMS, and Chua's signal denoising method, the signal-to-noise ratio (SNR) of this method increased by 23.22%, 26.46%, 18.79%, 16.11% the root mean square error (RMSE) decreased by 32.53%,39.48%, 30.96%, 27.94%, and the row entropy (PE) decreased by 40.44%, 41.96%, 22.78%, 20.59%; After reducing the radiation noise of cargo ships, the PE value of this method is reduced by 13.91%, 10.18%, 10.88%, 8.68% respectively, and the FE value is reduced by 33.66%, 31.42%, 26.98%, 21.32% respectively.

Effects of Different Injection Rates of Propofol on Postoperative Cognition in Elderly Patients Undergoing Laparoscopic Inguinal Hernia Repair.

Purpose: This study aimed to explore the effects of different injection rates of propofol on postoperative cognition in elderly patients undergoing laparoscopic inguinal hernia repair. Methods: A total of 180 elderly patients who planned to undergo laparoscopic inguinal hernia repair were randomly divided into three groups: slow injection of propofol (VS-Group, 30 mg kg-1 h-1); medium injection of propofol (VM-Group, 100 mg kg-1 h-1) or fast injection of propofol (VF-Group, 300 mg kg-1 h-1). Propofol was induced by microinfusion pump, and the depth of anesthesia was monitored by bispectral index (BIS). Propofol and remifentanil were continuously infused during anesthesia maintenance and adjusted according to BIS. The primary outcome was the use of the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) to measure the incidence of postoperative cognitive decline (POCD) in elderly patients on the first and seventh postoperative day. Secondary outcomes included induced dose of propofol, incidence of burst suppression and maximum electroencephalographic (EEG) effect of propofol (BIS-min) during induction. Results: The incidence of POCD on the first and seventh day postoperatively was similar among the three groups (P > 0.05). However, with the increase of propofol injection rate, induced dose of propofol, incidence of burst suppression and BIS-min during induction, the number of patients requiring vasoactive agents were significantly increased (P < 0.001). Multivariate regression analysis showed that the brief duration of burst suppression during induction did not affect the occurrence of POCD, while age and duration of hospitalization were risk factors for POCD. Conclusion: For elderly patients undergoing laparoscopic inguinal hernia repair, lowering the injection rate of propofol (such as 30 mg kg-1 h-1) cannot decrease the incidence of early POCD, but reduces induction dose of propofol and use of vasoactive drugs, making the patient's hemodynamics more stable.

Corrigendum: Flurbiprofen used in one-lung ventilation improves intraoperative regional cerebral oxygen saturation and reduces the incidence of postoperative delirium.

[This corrects the article DOI: 10.3389/fpsyt.2022.889637.].

Effects of α-lipoic acid on growth performance, antioxidant capacity, and immune function in sheep.

α-Lipoic acid (α-LA) was usually applied to improve the ability of removing the reactive oxygen species of host. The affection of α-LA on ruminants was mainly focused on the variation of serum antioxidant and immune indexes, but the research on tissues or organs remained limited. The aim of this study was to explore the effects of dietary supplementation with different levels of α-LA on growth performance, antioxidant status, and immune indexes of serum and tissues in sheep. One hundred Duhu F1 hybrid (Dupo♀ × Hu sheep♂) sheep aged 2 to 3 mo with similar body weight (27.49 ± 2.10 kg) were randomly allocated into five groups. Five diets supplemented with 0 (CTL), 300 (LA300), 450 (LA450), 600 (LA600), and 750 (LA750) mg/kg α-LA were fed to sheep for 60 d. The results showed that α-LA supplementation significantly increased the average daily feed intake (P < 0.05); however, no significant variation was found in the average daily gain, feed conversion rate, carcass weight, and slaughter rate among groups (P > 0.05). Compared with CTL group, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities in serum of LA600 and LA750 groups were increased (P < 0.05). At LA450-LA750 groups, SOD, CAT activities in liver and ileum tissues and GSH-Px activities in ileum tissues were increased than CTL group (P < 0.05), while malondialdehyde (MDA) contents in serum and muscle tissue were decreased than CTL group (P < 0.05). The total antioxidant capacity contents in liver, muscle, and ileum tissues of LA600 group were increased compared with CTL group (P < 0.05). Additionally, the interleukin-10 (IL-10) contents of serum in LA450-LA750 groups were increased than CTL group (P < 0.05); the contents of interleukin-1ß (IL-1ß) in serum, interleukin-2 (IL-2) in liver, and interleukin-6, IL-1ß in muscle were decreased than CTL group (P < 0.05). The content of immunoglobulin A in serum of LA600 group, ileum, and muscle of LA750 group was increased than CTL group (P < 0.05). Based on the quadratic regression analysis of GSH-Px, MDA, IL-2, IL-10, and IL-1ß, the optimal dietary α-LA levels were estimated to be 495.75, 571.43, 679.03, 749.75, and 678.25 mg/kg, respectively. This research will provide certain contribution for the effective utilization of α-LA in sheep production.

This article studied the effects of α-lipoic acid (α-LA) on growth performance, antioxidant capacity, and immune function of serum and tissues in sheep. α-LA was usually applied to improve the ability of removing the reactive oxygen species of host. The affection of α-LA on ruminants was mainly focused on the variation of serum antioxidant and immune indexes, but the research on tissues or organs remained limited. One hundred sheep aged 2 to 3 mo were randomly allocated into five groups; five diets supplemented with 0, 300, 450, 600, and 750 mg/kg α-LA were fed to sheep for 60 d. Results showed that adding appropriate α-LA in diet has the potential ability to improve the production performance, increase the activity of antioxidant enzymes, and regulate the secretion of inflammatory factors in sheep serum, rumen epithelium, liver, ileum, and muscle tissues. Therefore, these results indicated that α-LA has the potential to become a safe, high-quality, and environmentally friendly feed additive that could protect the health of sheep and improve the economic benefits of pasture.

Analysis, environmental occurrence, fate and potential toxicity of tire wear compounds 6PPD and 6PPD-quinone.

Tire wear compounds N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its derivative 6PPD-quinone have been considered as emerging pollutants and attracted much attention recently. As an antioxidant and antiozonant widely used, 6PPD would be released during the production or use of rubber-related products. Because of the mass production and wide use of rubber-related products, 6PPD and 6PPD-quinone have been identified to be ubiquitous in the environment. In this study, we firstly reviewed the current available literature on the analytical procedures, concentrations and distribution of 6PPD and 6PPD-quinone, and then investigated the potential toxic effects of these two compounds on aquatic organisms. Current studies have been mainly focused on the occurrence of 6PPD and 6PPD-quinone in dust and water, while available information on atmosphere, soil, sediments and organisms is limited. The fate and distribution of 6PPD and 6PPD-quinone would be influenced by environmental factors such as temperature, illumination, and storm events, etc. Although 6PPD and 6PPD-quinone have potential adverse effects on aquatic organisms, and 6PPD-quinone has species-specific toxicity, toxicological mechanisms of these compounds are still unclear. Based on the review and analysis of current studies, some suggestions for future research of 6PPD and 6PPD-quinone are given.

Application of Continuous Sacral Block Guided by Ultrasound After Comprehensive Sacral Canal Scanning in Children Undergoing Laparoscopic Surgery: A Prospective, Randomized, Double-Blind Study.

Purpose: The present study aimed to explore the effects of continuous sacral block on the postoperative pain of children and the satisfaction of the nurses in post-anesthesia care unit (PACU). Also, the influence of the modified protocol of continuous sacral block was investigated. Patients and Methods: A total of 60 children undergoing laparoscopic surgery were randomly divided into two groups: GI and GC groups. The general anesthesia was induced with midazolam, propofol, sufentanil and succinylcholine in both groups. In addition, the patients were subjected to continuous sacral block with levobupivacaine in group GC. The modified protocol of continuous sacral block was divided into three steps: comprehensive lumbar and sacral vertebral canal scanning by ultrasound, catheterization and administration. The EVENDOL pain scales and pediatric anesthesia emergence delirium scales of the children were evaluated at 5 min after extubation (T3), 90 min (T4), and 4 h (T5) after the operation. The nurses' satisfaction scores at T3 -T4 and adverse events, such as nausea and vomiting, were also recorded, after the operation. Results: After ultrasonic scanning, one patient in group GC was excluded due to the sacral hiatus atresia, which might lead to failure of catheterization. Data of 59 patients were collected for statistical analysis. Compared to the GI group, the EVENDOL scores and the pediatric anesthesia emergence delirium scales were reduced at T3, T4, and T5 (P < 0.05) in group GC. Furthermore, there was a higher rank of PACU nurses' satisfaction in the GC group compared to the GI group (P < 0.05). Conclusion: Based on the modified protocol, continuous sacral block provides reliable and safety analgesia for children undergoing laparoscopic surgery, thereby improving the satisfaction of PACU nurses.

Flurbiprofen used in one-lung ventilation improves intraoperative regional cerebral oxygen saturation and reduces the incidence of postoperative delirium.

Background: We previously demonstrated that flurbiprofen increased arterial oxygen partial pressure and reduced intrapulmonary shunts. The present study aims to investigate whether flurbiprofen improves intraoperative regional cerebral oxygen saturation (rScO2) and reduces the incidence of postoperative delirium (POD) in elderly patients undergoing one-lung ventilation (OLV). Methods: One hundred and twenty patients undergoing thoracoscopic lobectomy were randomly assigned to the flurbiprofen-treated group (n = 60) and the control-treated group (n = 60). Flurbiprofen was intravenously administered 20 minutes before skin incision. The rScO2 and partial pressure of arterial oxygen (PaO2) were recorded during the surgery, and POD was measured by the Confusion Assessment Method (CAM) within 5 days after surgery. The study was registered in the Chinese Clinical Trial Registry with the number ChiCTR1800020032. Results: Compared with the control group, treatment with flurbiprofen significantly improved the mean value of intraoperative rScO2 as well as the PaO2 value (P < 0.05, both) and significantly reduced the baseline values of the rScO2 area under threshold (AUT) (P < 0.01) at 15, 30, and 60 min after OLV in the flurbiprofen-treated group. After surgery, the POD incidence in the flurbiprofen-treated group was significantly decreased compared with that in the control group (P < 0.05). Conclusion: Treatment with flurbiprofen may improve rScO2 and reduce the incidence of POD in elderly patients undergoing thoracoscopic one-lung ventilation surgery for lung cancer. Clinical trial registration: http://www.chictr.org/cn/, identifier ChiCTR1800020032.

Effect of Perineural Dexamethasone with Ropivacaine in Continuous Serratus Anterior Plane Block for Postoperative Analgesia in Patients Undergoing Video-Assisted Thoracoscopic Surgery.

Purpose: The goal of this study was to evaluate the analgesic efficiency of dexamethasone with ropivacaine in continuous serratus anterior plane block (cSAPB) after video-assisted thoracoscopic surgery (VATS). Patients and Methods: Sixty-six patients who underwent VATS were randomized into two groups. All patients received cSAPB postoperatively, and patients in Group RD received 20 mL of 0.375% ropivacaine plus 0.1 mg/kg dexamethasone followed by an infusion of 0.2% ropivacaine plus 0.02 mg/kg/hour dexamethasone at a rate of 5 mL/h in patient-controlled analgesia (PCA) pump. Patients in Group R received 20 mL of 0.375% ropivacaine with normal saline followed by an infusion of 5 mL/h of 0.2% ropivacaine in PCA pump. Fifty milligrams of tramadol was given as rescue medication when the visual analog scale (VAS) score was ≥4 at rest. The primary outcomes were the sum of pressing number within 48 hours postoperatively and the time to the first patient-controlled bolus. The secondary outcomes were VAS scores, the incidence of rescue analgesia, wound infection and nausea/vomiting. Results: Within 48 hours postoperatively, the sum of pressing number was more in Group R (18.33 ± 3.149 vs 16.09 ± 3.292, P = 0.006), and the Log Rank Test showed a significant difference in time to the first patient-controlled bolus (P = 0.006). After the PCA infusion finished, there were significantly lower VAS scores in Group RD at 60 and 72 hours postoperatively (P < 0.001). Additionally, the incidence of rescue analgesia in Group R was significantly more than that in Group RD (P < 0.001). No incision infection was observed in any patient. Conclusion: The cSAPB with ropivacaine plus dexamethasone prolonged the duration of analgesia and motor blockade, reduced pain intensity and rescued analgesia requirements after the end of PCA infusion for patients undergoing VATS, which provide further improvement to continuous perineural block.

Retraction Notice to: FABP4 facilitates inflammasome activation to induce the Treg/Th17 imbalance in preeclampsia via forming a positive feedback with IL-17A.

[This retracts the article DOI: 10.1016/j.omtn.2021.03.020.].

Continuous Serratus Anterior Plane Block Improved Early Pulmonary Function After Lung Cancer Surgical Procedure.

BACKGROUND: Serratus anterior plane block (SAPB) has been proven to be an efficient way to control postoperative pain. This study explored whether the use of continuous SAPB in combination with flurbiprofen could improve early pulmonary function in lung cancer patients undergoing video-assisted thoracoscopic surgery (VATS). METHODS: From July 2019 to April 2020, patients who scheduled for elective lung resection undergoing VATS were randomly allocated to receive patient-controlled SAPB in combination with intravenous flurbiprofen or patient-controlled intravenous analgesia. Postoperative pulmonary function variables, including forced expiratory volume in 1 second, and forced vital capacity were collected before and 24, 48, and 72 hours after Surgical Procedure. Pain intensity was measured at rest and on coughing. Comfort scores during breathing exercises, postoperative pulmonary complications, and adverse events were recorded. RESULTS: A substantial reduction in lung function was exhibited in both groups after Surgical Procedure (P < .001), but lung function variables in the continuous SAPB group were significantly higher (P < .001) throughout the postoperative period up to 72 hours, regardless of the surgical procedure type. Meanwhile, there were significant differences of pain intensity at rest and on coughing between the groups (P < .001). The incidence of pneumonia, pulmonary atelectasis, hypoxemia, vomiting, and the comfort score in the continuous SAPB group was significantly lower (P < .05). CONCLUSIONS: Postoperative acute pain treatment with continuous SAPB in combination with flurbiprofen enhanced pulmonary function and reduced postoperative pulmonary complications in lung cancer patients undergoing VATS.

The Role of Serratus Anterior Plane Block During in Video-Assisted Thoracoscopic Surgery.

Although thoracoscopy has characteristics such as a small surgical incision and low stress response, post-surgical pain after a thoracoscopic operation is no less than that after a thoracotomy. Moreover, poor post-surgical pain management is likely to cause an increased incidence of postoperative pulmonary complications (PPCs) and chronic post-surgical pain. The serratus anterior plane block (SAPB) is a regional anesthesia method whereby local anesthetics (LAs) are injected into the serratus anterior space to block the lateral cutaneous branch of the intercostal nerve, long thoracic nerve, and dorsal thoracic nerve. The block range of the SAPB covers the incisions of video-assisted thoracoscopic surgery (VATS) and the site of the chest tube, which are often located in the antero-lateral chest wall. Therefore, the SAPB can achieve effective analgesia in VATS. For example, 0.125% to 0.25% levobupivacaine (20-25 ml) is widely used for thoracic surgery, which can achieve effective analgesia and avoid adverse reactions. Moreover, it has advantages compared with thoracic segmental epidural block (TEA) and thoracic paravertebral block (TPVB), such as simple operation, increased safety, fewer complications, and hemodynamic stability. In addition, adequate analgesia is helpful for pulmonary function recovery and reduces the incidence of PPCs. This article introduces the anatomical mechanism of the SAPB, diverse operation approaches, how to choose drugs and adjuvants, and the resulting impacted area range. It summarizes the advantages and disadvantages of the SAPB compared with other analgesic methods and posits that the SAPB is beneficial to the recovery of postoperative lung function, which provides more options for postoperative analgesia after VATS.

Pharmacokinetics and Bioequivalence Evaluation of 2 Formulations of Tenofovir Alafenamide.

The study was conducted to compare the pharmacokinetics and safety profiles of 2 brands of tenofovir alafenamide (TAF) fumarate tablets. This research was a 2-preparation, 2-sequence, 4-period crossover, completely replicated study in 68 healthy Chinese subjects under fasting and fed conditions. The mean values of the area under the concentration-time curve from time 0 to the last time point with blood sample collection (AUC0-t ), area under the concentration-time curve from time 0 to infinity (AUC0-∞ ), and maximum concentration (Cmax ) for the test and reference products of TAF were 248.5 and 275.7 ng/mL, 148.1 and 157.8 ng • h/mL, and 148.4 and 158.1 ng • h/mL, respectively, under the fasting condition. On the other hand, the mean value of Cmax , AUC0-t , and AUC0-∞ for the test and reference formulations of TAF were 244.6 and 246.7 ng/mL, 230.4 and 244.9 ng • h/mL, and 233.2 and 246.2 ng • h/mL, respectively, under the fed condition. The 90% confidence intervals for geometric mean ratios of AUC0-t and AUC0-∞ of TAF in fasting and fed states were within the bioequivalence acceptance limits when tested using the average-bioequivalence method. The point estimate value for geometric mean ratio of Cmax in fasting and fed states (88.4% and 95.5%, respectively) were within the bioequivalence acceptance limits as per the reference-scaled average-bioequivalence method. The safety profiles of the 2 formulations were comparable. Pharmacokinetic analysis demonstrated that the test formulations of TAF exhibited bioequivalence to the reference and were well tolerated by healthy Chinese subjects (Study Registry Identification Number: CTR20190086; CTR20190087).

The POM@MOF hybrid derived hierarchical hollow Mo/Co bimetal oxides nanocages for efficiently activating peroxymonosulfate to degrade levofloxacin.

Herein, we reported the design and fabrication of polyoxometalates coupling metal-organic framework (POM@MOF) hybrids derived hierarchical hollow Mo/Co bimetal oxides nanocages (Mo/Co HHBONs) for the peroxymonosulfate (PMS) activation to degrade levofloxacin (Lev). The Mo/Co HHBONs are hollow nanocages with high specific-surface areas and hierarchical micropores, mesopores, and macropores. In addition to compositional modulation, polyoxometalate (H3PMo12O40·nH2O) exhibited striking effect on the textural properties of Mo/Co HHBONs. The Mo/Co HHBONs had outstanding catalytic activity with first order-kinetics that were 6 - 10 times higher those previously reported. They exhibited good adaptability over a pH range of 3 - 11, as well as excellent universality and reusability. By altering the surface porosity, electronic structure, and oxygen vacancies of Co3O4, hetero-metal Mo doping induced Mo/Co HHBONs significantly promote the generation of reactive oxygen species, including •OH, SO4•-, O2•-, and 1O2. Density functional theory indicated that Mo/Co HHBONs had better adsorption, enhanced electron-transfer abilities, and a longer O-O bond length than did Co3O4, for improved catalytic reactivity. This research provides a new strategy to design the POM@MOF hybrids derived hierarchical hollow nanocages with highly PMS activating capacity for the removal of antibiotics and other refractory contaminants.

Preoperative angiotensin II type 2 receptor is a predictor for developing chronic post-surgical pain after total knee arthroplasty surgery.

OBJECTIVE: This study aimed to explore whether preoperative angiotensin II type 2 receptor (AT2R) level in knee osteoarthritis (OA) patients was an independent risk factor for chronic post-surgical pain (CPSP) after total knee arthroplasty (TKA). METHODS: A total of 220 patients who had undergone unilateral TKA were enrolled from October 2019 to January 2020. Quantitative sensory testing (QST), PainDETECT questionnaires (PD-Q), the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), the hospital anxiety and depression (HAD) and serum AT2R were collected preoperatively. The primary outcome was the incidence of CPSP, which was defined as the visual analogue scale (VAS) score ≥ 4 in the ipsilateral knee joint six months after operation. RESULTS: The prevalence of CPSP was 13.6% (n = 30). Multiple logistic regression analysis showed that patients with higher AT2R level (OR: 1.007, 95% CI: 1.003-1.011) and PD-Q score (OR: 1.146, 95% CI: 1.008-1.298) before surgery had an increased risk of CPSP after surgery, and a combination of preoperative AT2R and PD-Q (Akaike information criterion: 147.2; area under receiver operating characteristic (ROC) curve: 0.890) was able to correctly classify 90.16% of patients into CPSP positive or negative groups. CONCLUSION: Our findings suggest that patients with higher preoperative AT2R level are at increased risk of developing CPSP following TKA. AT2R may serve as a candidate predictor for phenotyping CPSP in OA patients.

FABP4 facilitates inflammasome activation to induce the Treg/Th17 imbalance in preeclampsia via forming a positive feedback with IL-17A.

Preeclampsia (PE) is one of the leading causes of maternal death worldwide. Elevated fatty acid binding protein 4 (FABP4) levels have been observed in patients with PE, however, the mechanism by which FABP4 contributes to the pathogenesis of PE remains unclear. In this study, we compared the levels of FABP4 and cytokines between 20 PE patients and 10 healthy pregnant women by using ELISA, immunohistochemistry (IHC) analysis, and flow cytometry (fluorescence-activated cell sorting, FACS). Elevated FABP4 was accompanied by regulatory T (Treg)/T helper type 17 (Th17) imbalance in PE. Knockdown of FABP4 attenuated lipopolysaccharide (LPS)-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and interleukin-17A (IL-17A) production in primary macrophages. In addition, silencing of FABP4 also suppressed Th17 differentiation via paracrine signaling. Overexpression of FABP4 promoted Th17 differentiation via increasing IL-17A/IL-23 release. Reciprocally, IL-17A upregulated FABP4 and activated the NLRP3 inflammasome in vitro and in vivo. The in vivo studies revealed that FABP4 inhibitor BMS309403 ameliorated PE clinical phenotypes, the Treg/Th17 imbalance, and NLRP3 inflammasome activation in PE mice model. In conclusion, FABP4 facilitates inflammasome activation to induce the imbalance of Treg/Th17 in PE via forming a positive feedback with IL-17A.

Sufentanil Protects the Liver from Ischemia/Reperfusion-Induced Inflammation and Apoptosis by Inhibiting ATF4-Induced TP53BP2 Expression.

Liver ischemia-reperfusion (I/R) injury is a pathological process that often occurs during liver and trauma surgery. This study aimed to investigate the protective effect and potential mechanisms of sufentanil on hepatic I/R injury. I/R rat model and hypoxic/reoxygenation (H/R)-induced buffalo rat liver (BRL)-3A cell model were established. Following pretreatment with sufentanil, the enzymatic activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in rat serum and the changes of hepatic histopathology were evaluated to track the extent of liver injury. The levels of inflammatory factors were determined with ELISA kits and RT-qPCR. The infiltration of macrophages was assessed after detecting monocyte chemoattractant protein 1 (MCP-1) and F4/80 expression. Additionally, apoptosis was measured by means of TUNEL staining, and gene expression related to apoptosis was examined using RT-qPCR and western blotting. Then, TP53BP2 was overexpressed in BRL-3A cells exposed to H/R condition to evaluate whether sufentanil defended the liver against injury by regulating TP53BP2 expression. Moreover, the potential binding site of ATF4 on the TP53BP2 promoter was analyzed using JASPAR databases and verified by chromosomal immunoprecipitation (ChIP) assay. Furthermore, TP53BP2 expression and endoplasmic reticulum stress (ERS)-related protein levels were determined after ATF4 was overexpressed in sufentanil-treated BRL-3A cells. Results revealed that sufentanil significantly improved hepatic I/R injury, decreased the levels of inflammatory factors, and alleviated hepatocyte apoptosis. Notably, upregulated TP53BP2 expression was observed in hepatic tissues, and TP53BP2 overexpression markedly reversed the protective effects of sufentanil on the inflammation and apoptosis in H/R-stimulated BRL-3A cells. Additionally, ATF4 was confirmed to combine with the TP53BP2 promoter. ATF4 upregulation attenuated the inhibitory effects of sufentanil on the expression of TP53BP2 and ERS-associated proteins. These findings demonstrated that sufentanil protects the liver from inflammation and apoptosis injury induced by I/R by inhibiting ATF4 expression and further suppressing TP53BP2 expression, suggesting a promising therapeutic candidate for the treatment of liver I/R injury.

Hong-Hui-Xiang Alleviates Pain Hypersensitivity in a Mouse Model of Monoarthritis.

Background: Hong-Hui-Xiang (HHX) is a sterilized aqueous solution extracted from Illicium lanceolatum A.C. Smith widely used for pain relief in China. Despite its history, it is not well understood. In the present study, we used a mouse model of arthritic knee pain to investigate the antinociceptive effects of HHX and its potential side effects on weight and respiratory function, as well as on the liver, kidney, and heart. Methods: Mice were randomly assigned to four groups: saline and HHX at three doses (1 µl, 10 µl, and 50 µl). Each group was randomly divided to two subgroups: saline and CFA. After the first injection of HHX or saline on day 7, mechanical hyperalgesia was tested via the hind paw. Only after the tests had established that the analgesic effect had subsided was the next injection administered. A total of five injections were administered. Blood, knee joints, and other organs were collected for histopathological observation and biochemical detection. Objectives: We found that mechanical threshold of hind paw increased 2 h after of the initial injection HHX (10 µl and 50 µl), which lasted for at least 3 h. The analgesic effect lasted for three days after the second injection on day 8 and was approximately maintained for five days each time after the third injection. We also found a reduction in the diameter of the knee joint and suppression of synovial inflammation in response to treatment of HHX (10 µl and 50 µl). Meanwhile, HHX had no toxic effects on the liver, kidneys, and heart via histological and biochemical assays in all groups. Conclusion: HHX exerts antinociceptive and anti-inflammatory effects in a mouse model of arthritic knee pain. There were no obvious side effects on the liver, kidneys, or heart.