Electroacupuncture treatment improves postoperative ileus by inhibiting the Th1 cell-mediated inflammatory response through the vagus nerve.

BACKGROUND: Electroacupuncture (EA) has been reported to improve intestinal motility in mice with postoperative ileus (POI). Previous studies, however, have yielded heterogeneous results regarding the effect of EA on POI. METHODS: Herein, a POI mouse model was constructed by intestinal manipulation. To evaluate the effect of EA treatment on colonic transit, the levels of inflammatory markers (macrophage inflammatory protein (MIP)-1α, interleukin (IL)-1ß, IL-6, monocyte chemotactic protein (MCP)-1 and intercellular adhesion molecule (ICAM)-1) were detected by enzyme-linked immunosorbent assay (ELISA); immune cell infiltration was detected by immunohistochemical staining of myeloperoxidase (MPO), ectodysplasin (ED)-1 and ED-2, and the percentage of CD4+ interferon (IFN)-γ+ Th1 cells and IFN-γ secretion levels were determined. Activated Th1 cells and pentoxifylline, a cell differentiation inhibitor, were used to assess the role of Th1 cells in EA treatment of POI. Neostigmine administration and unilateral vagotomy were performed to confirm whether the effects of EA treatment on Th1 cells were mediated by the vagus nerve (VN). RESULTS: The results revealed that EA treatment at ST36 improved POI, as indicated by a decreased level of inflammatory-related markers and immune cell infiltration and shortened colonic transit time. The activated Th1 cells abolished the effects of EA treatment on POI. The effects of EA treatment on POI were enhanced by stimulation of the VN along with a decreased level of Th1 cells, but these effects were abolished by vagotomy along with an increased percentage of Th1 cells; this result indicates that the VN mediates the role of Th1 cells in the effects of EA treatment of POI. CONCLUSION: Our findings showed that the effects of EA treatment of POI were mainly mediated by Th1 cells through the stimulation of the VN and inhibition of the inflammatory response.

Ocular biomarkers of cognitive decline based on deep-learning retinal vessel segmentation.

BACKGROUND: The current literature shows a strong relationship between retinal neuronal and vascular alterations in dementia. The purpose of the study was to use NFN+ deep learning models to analyze retinal vessel characteristics for cognitive impairment (CI) recognition. METHODS: We included 908 participants from a community-based cohort followed for over 15 years (the prospective KaiLuan Study) who underwent brain magnetic resonance imaging (MRI) and fundus photography between 2021 and 2022. The cohort consisted of both cognitively healthy individuals (N = 417) and those with cognitive impairment (N = 491). We employed the NFN+ deep learning framework for retinal vessel segmentation and measurement. Associations between Retinal microvascular parameters (RMPs: central retinal arteriolar / venular equivalents, arteriole to venular ratio, fractal dimension) and CI were assessed by Pearson correlation. P < 0.05 was considered statistically significant. The correlation between the CI and RMPs were explored, then the correlation coefficients between CI and RMPs were analyzed. Random Forest nonlinear classification model was used to predict whether one having cognitive decline or not. The assessment criterion was the AUC value derived from the working characteristic curve. RESULTS: The fractal dimension (FD) and global vein width were significantly correlated with the CI (P < 0.05). Age (0.193), BMI (0.154), global vein width (0.106), retinal vessel FD (0.099), and CRAE (0.098) were the variables in this model that were ranked in order of feature importance. The AUC values of the model were 0.799. CONCLUSIONS: Establishment of a predictive model based on the extraction of vascular features from fundus images has a high recognizability and predictive power for cognitive function and can be used as a screening method for CI.

Randomized Controlled Trial Investigating the Impact of High-Flow Nasal Cannula Oxygen Therapy on Patients Undergoing Robotic-Assisted Laparoscopic Rectal Cancer Surgery, with a Post-Extubation Atelectasis as a Complication.

Background: Utilizing high-flow nasal cannula (HFNC) oxygen therapy may prevent the collapse of alveoli and improve overall alveolar ventilation. In this study, we aimed to investigate the impact of HFNC on postoperative atelectasis in individuals undergoing robotic-assisted laparoscopic surgery. Methods: Patients undergoing robotic-assisted laparoscopic surgery for rectal cancer were randomly assigned to the control or HFNC groups. After the surgical procedure was complete and the trachea was extubated, both groups underwent an initial lung ultrasound (LUS) scan. In the post-anesthesia care unit (PACU), the control group received conventional nasal cannula oxygen therapy, while the HFNC group received high-flow nasal cannula oxygen therapy. A second LUS scan was conducted before the patient was transferred to the ward. The primary outcome measured was the total LUS score at the time of PACU discharge. Results: In the HFNC group (n = 39), the LUS score and the incidence of atelectasis at PACU discharge were significantly lower compared to the control group (n = 39) [(5 vs 10, P < 0.001), (48.72% vs 82.05%, P = 0.002)]. None of the patients in the HFNC group experienced hypoxemia in the PACU, whereas six patients in the control group did (P = 0.03). Additionally, the minimum SpO2 value in the PACU was notably higher in the HFNC group compared to the control group [99 vs 97, P < 0.001]. Conclusion: Based on the results, HFNC improves the extent of postoperative atelectasis and decreases the occurrence of atelectasis in individuals undergoing robotic-assisted laparoscopic surgery for rectal cancer.

Efficacy and safety of electrical acupoint stimulation for postoperative nausea and vomiting: A systematic review and meta-analysis.

BACKGROUND: Postoperative nausea and vomiting are typical postsurgical complications. Drug therapy is only partially effective. The goal of our meta-analysis is to systematically evaluate the efficacy and safety of electrical acupoint stimulation for postoperative nausea and vomiting and to score the quality of evidence supporting this concept. METHODS: PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched from inception to March 19, 2020. RESULTS: Twenty-six studies (2064 patients) were included. Compared with control treatment, electrical acupoint stimulation reduced the incidence of postoperative nausea and vomiting (RR 0.49, 95% CI 0.41 to 0.57, P < 0.001), postoperative nausea (RR 0.55, 95% CI 0.47 to 0.64, P < 0.001) and postoperative vomiting (RR 0.56, 95% CI 0.45 to 0.70, P < 0.001). Electrical acupoint stimulation also reduced the number of patients requiring antiemetic rescue (RR 0.60, 95% CI 0.43 to 0.85, P = 0.004). No differences in adverse events were observed. Subgroup analysis showed that both electroacupuncture (RR 0.58, 95% CI 0.46 to 0.74, P < 0.001) and transcutaneous electrical acupoint stimulation (RR 0.44, 95% CI 0.34 to 0.58, P < 0.001) had significant effects. Electrical acupoint stimulation was effective whether administered preoperatively (RR 0.40, 95% CI 0.27 to 0.60, P < 0.001), postoperatively (RR 0.59, 95% CI 0.46 to 0.76, P < 0.001), or perioperatively (RR 0.50, 95% CI 0.37 to 0.67, P < 0.001). The quality of evidence was moderate to low. CONCLUSIONS: Electrical acupoint stimulation probably reduce the incidence of postoperative nausea and vomiting, postoperative nausea, postoperative vomiting, and reduce the number of patients requiring antiemetic rescue, with few adverse events.

Pain Trajectory after Short-Stay Anorectal Surgery: A Prospective Observational Study.

The evolution of pain after anorectal surgery has not been well characterized. The main objective of this study is to evaluate patterns in acute postoperative pain in patients undergoing short-stay anorectal surgery. A total of 217 patients were included in the study, which used group-based trajectory modeling to estimate postoperative pain and then examined the relationships between sociodemographic or surgical factors and pain trajectories. Three distinct postoperative pain trajectories were determined: hemorrhoidectomy (OR, 0.15), higher anxiety (OR, 3.26), and a higher preoperative pain behavior score (OR, 3.15). In multivariate analysis, they were associated with an increased likelihood of being on the high pain trajectory. The pain trajectory group was related to postoperative analgesic use (p < 0.001), with the high-low group needing more nonsteroidal analgesics. The study showed that there were three obvious pain trajectories after anorectal surgery, including an unreported low-moderate-low type. More than 60% of patients maintained moderate to severe pain within 7 days after the operation. These postoperative pain trajectories were predominantly defined by surgery factors and patient factors.

Safety and biodistribution of exosomes derived from human induced pluripotent stem cells.

As a new cell-free therapy, exosomes have provided new ideas for the treatment of various diseases. Human induced pluripotent stem cells (hiPSCs) cannot be used in clinical trials because of tumorigenicity, but the exosomes derived from hiPSCs may combine the advantages of iPSC pluripotency and the nanoscale size of exosomes while avoiding tumorigenicity. Currently, the safety and biodistribution of hiPSC-exosomes in vivo are unclear. Here, we investigated the effects of hiPSC-exosomes on hemolysis, DNA damage, and cytotoxicity through cell experiments. We also explored the safety of vein injection of hiPSC-exosomes in rabbits and rats. Differences in organ distribution after nasal administration were compared in normal and Parkinson's disease model mice. This study may provide support for clinical therapy and research of intravenous and nasal administration of hiPSC-exosomes.

[Simulation of gas chromatographic separation based on random diffusion].

Understanding the diffusion behavior of particles during chromatographic analysis is critical for optimizing the operation conditions, improving the chromatographic performance, and designing a new separation device. Most of the existing simulations focus on chromatographic thermodynamics, while very few consider the overall diffusion and separation process. Herein, a new simulation method for gas chromatography separation was developed based on the random diffusion theory in microscale restricted space. This method retained the key information for controlling the diffusion behavior, simplified the interaction between the particles to be separated, and enlarged the time scale of each step one molecule walks. Thus, the operational efficiency could be significantly improved due to reduced calculation, and the entire diffusion process in the gas chromatography capillary column could be simulated. In this model, the capillary column was represented by a two-dimensional long and narrow rectangle where the particles to be separated randomly diffused. Besides, a directional velocity along the axis of the chromatographic column exerted on the particle represented the driving force of the mobile phase. If a particle collided with the inner wall of the column, it would remain at the collision position even after some time lapsed. When desorption occured, the particle would flow along with the mobile phase until its next adsorption on the surface. The interaction between the particle and the inner wall was expressed by the equivalent adsorption time. By dynamically tracking the trajectories of particles, the statistical distribution of time for the residence of the particles in the chromatographic column could be obtained, that is, the detection signal (retention time). Based on the previous simulation studies on the separation of n-alkane homologues, combined with the Kovats Retention Index, the functional relationships between adsorption steps and temperature as well as carbon number were established. As a result, the separation parameter systems for various homologues at different temperatures were set up. The separation of alcohol homologues at different temperatures was considered as an example to verify the reliability of the simulation method. The relative errors between the measured and simulated values were within 5% for the retention time and 0.75%-60% for the peak width. The reasons for the large relative errors in the peak width are summarized as follows. On the one hand, parameterization of alcohol homologues was performed on the basis of a previous study on the separation law of n-alkane. Given the limitations of the current computing capability, the insufficient iteration in the parameterized process led to large errors. In addition, the errors at different temperatures further accumulated in extrapolated approximations. On the other hand, the strong hydrogen bond force between the alcohol molecules was simplified with the elastic collision, which increased the magnitude of the errors. Although the simulation method proposed in this paper can accurately predict the retention time and reasonably describe the morphological characteristics of chromatographic peaks, there is still room for improvement. In particular, the description of the detailed interactions between molecules must be improved. For example, the method of molecular mechanics may be assistant with the investigation of the functional relationship between interaction potential and adsorption steps. The interaction potential calculated on the basis of molecular mechanics replaces the parameterized adsorption steps, yielding more accurate simulation results. In general, the simulation method proposed in this study is a valuable reference for the optimization of chromatographic operating conditions and for the development of new chromatographic techniques.

Electroacupuncture treatment ameliorated the long-term cognitive impairment via activating eNOS/NO pathway and related Aß downregulation in sepsis-survivor mice.

OBJECTIVE: Sepsis is a major challenge in intensive care unit worldwide and the septic survivors are left with long-term cognitive deficits. This work aims to explore the effects of electroacupuncture (EA) on long-term cognitive function and its underlying mechanism in sepsis-survivor mice. METHODS: Sepsis was induced by cecal ligation and puncture in C57BL/6 male mice. Seven days post-surgery, sepsis-survivor mice were treated with EA or nonacupoint EA for 17 days twice daily. Then, cognitive function was evaluated by Morris water maze task. The hippocampus tissue were collected from the mice at 30 days post-surgery. The level of nitric oxide and the expression of endothelial nitric oxide (eNOS), phospho-eNOS (p-eNOS), and amyloid ß-peptide (Aß) were measured. RESULTS: Compared with the sham-operated control, sepsis-survivors had significant cognitive deficits evidenced by the increased time of escape latency and reduced crossing number in Morris water maze task, as well as lower NO and p-eNOS level and higher Aß level. EA treatment at GV20 and ST36 acupoints but not at a nonacupoint improved the cognitive function, increased the NO and p-eNOS level, and decreased Aß generation; while eNOS inhibitor (l-NAME) undermined the efficacy of EA treatment. CONCLUSION: In conclusion, repeated EA treatment could ameliorate the long-term cognitive impairment via manipulating the expression of p-eNOS and related Aß in sepsis-survivor mice.

Diastereoselective Synthesis of Adjacent P,C-Stereogenic ß-N-Glycosidic Linked α-Aminophosphinates.

The diastereoselective formation of adjacent P,C-stereogenic ß-N-glycosidic linked α-aminophosphinates is developed in high yields via a phospha-Mannich reaction. The reaction was performed by employing (Rp)-O-(-)-menthyl H-phenylphosphinate and O-pivaloylated N-galactosylimine for double stereodifferentiation and BF3·Et2O as a promoter in THF. O-Pivaloylated N-galactosylphenyl imine 2 and (Rp)-O-(-)-menthyl H-phenylphosphinate 1 were converted to N-galactosyl α-aminoalkylphosphinate 3 with ratios of diastereomers up to 20:1. The synthetic method of the conversion provides a rapid access to adjacent P,C-stereogenic chiral α-aminophosphinates.

Antinociceptive effects of dehydrocorydaline in mouse models of inflammatory pain involve the opioid receptor and inflammatory cytokines.

Dehydrocorydaline (DHC) is an alkaloidal component isolated from Rhizoma corydalis. Previous studies have shown that DHC has anti-inflammatory and anti-tumor effects and that it can protect the cardiovascular system. However, there are few studies of the antinociceptive effects of DHC in vivo. This study explored the antinociceptive effects and possible mechanisms of DHC in mice using two inflammatory pain models: the acetic acid-induced writhing test and the formalin paw test. The intraperitoneal administration of DHC (3.6, 6 or 10 mg/kg) showed a dose-dependent antinociceptive effect in the acetic acid-induced writhing test and significantly attenuated the formalin-induced pain responses in mice. The antinociceptive effects of DHC were not associated with changes in the locomotor activity or motor responses of animals, and no obvious acute or chronic toxic effects were observed in the mice. Furthermore, the use of naloxone confirmed the involvement of the opioid receptor in the central antinociceptive effects of DHC. DHC reduced formalin-induced paw edema, which indicated that DHC may produce an anti-inflammatory effect in the periphery. In the formalin test, DHC decreased the expression of caspase 6 (CASP6), TNF-α, IL-1ß and IL-6 proteins in the spinal cord. These findings confirm that DHC has antinociceptive effects in mice.

[Influencing factors of local immunocyte infiltration in hepatocellular carcinoma tissues pre- and post-percutaneous microwave coagulation therapy].

OBJECTIVE: To investigate the influencing factors of the local immunity in tissues of hepatocellular carcinoma (HCC) before and after percutaneous microwave coagulation therapy (PMCT). METHODS: Seventy-eight patients with HCC diagnosed by needle biopsy of liver underwent PMCT. Before the treatment and three and 17 days after the treatment specimens of carcinoma tissues were obtained by ultrasound-guided liver biopsy. The extents of infiltration of CD3(+) cell, natural killer cells (CD56(+)), and macrophages (CD68(+)), and the expression rate of proliferating cell nuclear antigen (PCNA) were evaluated by immunohistochemistry. The relation between the extents of immunocyte infiltration and the clinical parameters was analyzed with multiple regression. RESULTS: Before PMCT infiltration of the three kinds of immunocytes was found in the carcinoma tissues to different degrees with a great variation among individuals. A remarkable increase in the extent of infiltration of the three kinds of immunocytes was found three days after the treatment and continued or remained till the 17th post-PMCT day (P < 0.01). The post-PMCT extent of immunocyte infiltration was positively correlated with the pre-PMCT extent (CD3(+): r = 0.256, P = 0.005; CD56(+): r = 0.257, P = 0.002; CD68(+): r = 0.275, P = 0.001). A negative correlation was found between the extent of immunocyte infiltration and serum alpha-fetal protein (AFP) and between the extent of immunocyte infiltration and tumor size (for serum AFP, CD3(+): r = -0.075, P = 0.049; CD56(+): r = -0.062, P = 0.041; CD68(+): r = -0.007, P = 0.035; for tumor size, CD3(+): r = -0.074, P = 0.051; CD56(+): r = -0.100, P = 0.012; CD68(+): r = -0.109, P = 0.038). No correlation was found between the extent of immunocyte infiltration and age of patient, Child-Pugh class of tumor, grade of tumor differentiation, and number of tumor. The extent of immunocyte infiltration was lesser in the carcinoma tissues with higher expression rate of PCNA. The extent of immunocyte infiltration was greater in the carcinoma tissues where PCNA expression was negative and carcinoma cells had necrotized but with their structure recognizable. No immunocyte infiltration was found in the necrotic and structureless tumor tissues. CONCLUSION: The local immunocyte infiltration in patients with HCC was influenced by serum AFP and the grade of tumor cell necrosis pre- and post-PMCT. Destruction of tumor tissue in situs by PMCT is the premise of increase of immunocyte infiltration. Before PMCT improving the immune status of the patients helps enhance the local immune response.